European Society for Therapeutic Radiology and Oncology (ESTRO): International Oncology Forum

LONDON – An antiviral agent normally used to treat an AIDS-associated complication could increase the sensitivity of cancers associated with human papillomaviruses to chemoradiotherapy, according to preliminary study findings.

As reported at the European Society for Therapeutic Radiation Oncology Anniversary Conference, cidofovir appears to increase the sensitivity of locally advanced cervical carcinomas to the effects of radiotherapy and chemotherapy. It has resulted in no local failures or toxicities in 10 patients treated to date in an ongoing phase I dose escalation study.

Although still in very early days, the novel approach holds promise for using the antiviral agent as a possible radiosensitizer in HPV-related cancers, researchers at the Institut Gustave-Roussy in Villejuif, France, believe.

HPV infection has been associated with the development of several tumor types, including cervical, head and neck, and anal carcinoma, Dr. Eric Deutsch, a professor of radiation oncology at the institute, explained at a press briefing on May 11 .

"We know a lot about the underlying molecular mechanisms of HPV infection," Dr. Deutsch observed. "We know that HPV oncogenes [E6 and E7] are in fact dis-repairing tumor suppressor genes, and this is clearly associated with tumor progression and resistance to therapies."

Preclinical research has shown that cidofovir can prevent the transformation of HPV-infected cervical cells (Oncogene 2002;21:2334-46), and that it has antiangiogenic and antimetastatic activity (PLoS One 2009;4:e5018), Dr. Deutsch noted. Thus, it could be used as a potential adjunct to current therapy to improve the outcome of more than 10,800 women who are diagnosed with cervical cancer in the United States each year. In all, 24,900 HPV-related cancers occur each year in the U.S., according to Dr. Deutsch.

Cidofovir (Vistide) is an injectable antiviral drug approved for a very specific indication – the treatment of retinal inflammation due to cytomegalovirus in patients with AIDS. The fact that the drug is approved means that it is a known entity, and this could help fast-track its use if supported by suitable evidence.

On the basis of the preclinical evidence, Dr. Deutsch and his colleagues have initiated a phase I clinical trial in patients with locally advanced cervical cancer. Although cidofovir is not a new agent, a phase I trial is needed as the drug is being used in combination with the standard therapy for cervical cancer – and it’s important to show that there are no dose-limiting toxicities. According to the cidofovir package insert, patients need to be monitored closely for acute renal failure and neutropenia.

In the trial, the antiviral agent is being given once weekly and patients receive external-beam pelvic radiotherapy (45 Gy in 1.8-Gy fractions) plus carboplatin, followed by brachytherapy and chemotherapy. The dose levels explored so far range up to 5 mg/kg during the full course of radiotherapy, and no dose-limiting toxicities have been observed after up to 2 years for some doses. No local failures have been reported.

Target accrual is 12 patients, and a 10-patient extension is planned to evaluate efficacy. Phase I should be complete this year, and phase II in 2011-2012.

Although these data are preliminary, they indicate that cidofovir could be a potential radiosensitizer, Dr. Deutsch said. The fact that no toxicities have been seen to date also suggests that the risk-benefit ratio could favor combining the antiviral with radiation and chemotherapy. Phase II/III studies will be needed to confirm these results.

Dr. Deutsch noted that these findings could also potentially produce a quicker solution to tackling the problem of HPV-associated cancers, as current vaccination programs will need between 1 and 2 decades’ lead time before they could have any real effect.

The study is sponsored by the Institut Gustave Roussy. Dr. Deutsch did not state any conflicts of interest.

LONDON – An antiviral agent normally used to treat an AIDS-associated complication could increase the sensitivity of cancers associated with human papillomaviruses to chemoradiotherapy, according to preliminary study findings.

As reported at the European Society for Therapeutic Radiation Oncology Anniversary Conference, cidofovir appears to increase the sensitivity of locally advanced cervical carcinomas to the effects of radiotherapy and chemotherapy. It has resulted in no local failures or toxicities in 10 patients treated to date in an ongoing phase I dose escalation study.

Although still in very early days, the novel approach holds promise for using the antiviral agent as a possible radiosensitizer in HPV-related cancers, researchers at the Institut Gustave-Roussy in Villejuif, France, believe.

HPV infection has been associated with the development of several tumor types, including cervical, head and neck, and anal carcinoma, Dr. Eric Deutsch, a professor of radiation oncology at the institute, explained at a press briefing on May 11 .

"We know a lot about the underlying molecular mechanisms of HPV infection," Dr. Deutsch observed. "We know that HPV oncogenes [E6 and E7] are in fact dis-repairing tumor suppressor genes, and this is clearly associated with tumor progression and resistance to therapies."

Preclinical research has shown that cidofovir can prevent the transformation of HPV-infected cervical cells (Oncogene 2002;21:2334-46), and that it has antiangiogenic and antimetastatic activity (PLoS One 2009;4:e5018), Dr. Deutsch noted. Thus, it could be used as a potential adjunct to current therapy to improve the outcome of more than 10,800 women who are diagnosed with cervical cancer in the United States each year. In all, 24,900 HPV-related cancers occur each year in the U.S., according to Dr. Deutsch.

Cidofovir (Vistide) is an injectable antiviral drug approved for a very specific indication – the treatment of retinal inflammation due to cytomegalovirus in patients with AIDS. The fact that the drug is approved means that it is a known entity, and this could help fast-track its use if supported by suitable evidence.

On the basis of the preclinical evidence, Dr. Deutsch and his colleagues have initiated a phase I clinical trial in patients with locally advanced cervical cancer. Although cidofovir is not a new agent, a phase I trial is needed as the drug is being used in combination with the standard therapy for cervical cancer – and it’s important to show that there are no dose-limiting toxicities. According to the cidofovir package insert, patients need to be monitored closely for acute renal failure and neutropenia.

In the trial, the antiviral agent is being given once weekly and patients receive external-beam pelvic radiotherapy (45 Gy in 1.8-Gy fractions) plus carboplatin, followed by brachytherapy and chemotherapy. The dose levels explored so far range up to 5 mg/kg during the full course of radiotherapy, and no dose-limiting toxicities have been observed after up to 2 years for some doses. No local failures have been reported.

Target accrual is 12 patients, and a 10-patient extension is planned to evaluate efficacy. Phase I should be complete this year, and phase II in 2011-2012.

Although these data are preliminary, they indicate that cidofovir could be a potential radiosensitizer, Dr. Deutsch said. The fact that no toxicities have been seen to date also suggests that the risk-benefit ratio could favor combining the antiviral with radiation and chemotherapy. Phase II/III studies will be needed to confirm these results.

Dr. Deutsch noted that these findings could also potentially produce a quicker solution to tackling the problem of HPV-associated cancers, as current vaccination programs will need between 1 and 2 decades’ lead time before they could have any real effect.

The study is sponsored by the Institut Gustave Roussy. Dr. Deutsch did not state any conflicts of interest.

LONDON – An antiviral agent normally used to treat an AIDS-associated complication could increase the sensitivity of cancers associated with human papillomaviruses to chemoradiotherapy, according to preliminary study findings.

As reported at the European Society for Therapeutic Radiation Oncology Anniversary Conference, cidofovir appears to increase the sensitivity of locally advanced cervical carcinomas to the effects of radiotherapy and chemotherapy. It has resulted in no local failures or toxicities in 10 patients treated to date in an ongoing phase I dose escalation study.

Although still in very early days, the novel approach holds promise for using the antiviral agent as a possible radiosensitizer in HPV-related cancers, researchers at the Institut Gustave-Roussy in Villejuif, France, believe.

HPV infection has been associated with the development of several tumor types, including cervical, head and neck, and anal carcinoma, Dr. Eric Deutsch, a professor of radiation oncology at the institute, explained at a press briefing on May 11 .

"We know a lot about the underlying molecular mechanisms of HPV infection," Dr. Deutsch observed. "We know that HPV oncogenes [E6 and E7] are in fact dis-repairing tumor suppressor genes, and this is clearly associated with tumor progression and resistance to therapies."

Preclinical research has shown that cidofovir can prevent the transformation of HPV-infected cervical cells (Oncogene 2002;21:2334-46), and that it has antiangiogenic and antimetastatic activity (PLoS One 2009;4:e5018), Dr. Deutsch noted. Thus, it could be used as a potential adjunct to current therapy to improve the outcome of more than 10,800 women who are diagnosed with cervical cancer in the United States each year. In all, 24,900 HPV-related cancers occur each year in the U.S., according to Dr. Deutsch.

Cidofovir (Vistide) is an injectable antiviral drug approved for a very specific indication – the treatment of retinal inflammation due to cytomegalovirus in patients with AIDS. The fact that the drug is approved means that it is a known entity, and this could help fast-track its use if supported by suitable evidence.

On the basis of the preclinical evidence, Dr. Deutsch and his colleagues have initiated a phase I clinical trial in patients with locally advanced cervical cancer. Although cidofovir is not a new agent, a phase I trial is needed as the drug is being used in combination with the standard therapy for cervical cancer – and it’s important to show that there are no dose-limiting toxicities. According to the cidofovir package insert, patients need to be monitored closely for acute renal failure and neutropenia.

In the trial, the antiviral agent is being given once weekly and patients receive external-beam pelvic radiotherapy (45 Gy in 1.8-Gy fractions) plus carboplatin, followed by brachytherapy and chemotherapy. The dose levels explored so far range up to 5 mg/kg during the full course of radiotherapy, and no dose-limiting toxicities have been observed after up to 2 years for some doses. No local failures have been reported.

Target accrual is 12 patients, and a 10-patient extension is planned to evaluate efficacy. Phase I should be complete this year, and phase II in 2011-2012.

Although these data are preliminary, they indicate that cidofovir could be a potential radiosensitizer, Dr. Deutsch said. The fact that no toxicities have been seen to date also suggests that the risk-benefit ratio could favor combining the antiviral with radiation and chemotherapy. Phase II/III studies will be needed to confirm these results.

Dr. Deutsch noted that these findings could also potentially produce a quicker solution to tackling the problem of HPV-associated cancers, as current vaccination programs will need between 1 and 2 decades’ lead time before they could have any real effect.

The study is sponsored by the Institut Gustave Roussy. Dr. Deutsch did not state any conflicts of interest.

LONDON – An antiviral agent normally used to treat an AIDS-associated complication could increase the sensitivity of cancers associated with human papillomaviruses to chemoradiotherapy, according to preliminary study findings.

As reported at the European Society for Therapeutic Radiation Oncology Anniversary Conference, cidofovir appears to increase the sensitivity of locally advanced cervical carcinomas to the effects of radiotherapy and chemotherapy. It has resulted in no local failures or toxicities in 10 patients treated to date in an ongoing phase I dose escalation study.

Although still in very early days, the novel approach holds promise for using the antiviral agent as a possible radiosensitizer in HPV-related cancers, researchers at the Institut Gustave-Roussy in Villejuif, France, believe.

HPV infection has been associated with the development of several tumor types, including cervical, head and neck, and anal carcinoma, Dr. Eric Deutsch, a professor of radiation oncology at the institute, explained at a press briefing on May 11 .

"We know a lot about the underlying molecular mechanisms of HPV infection," Dr. Deutsch observed. "We know that HPV oncogenes [E6 and E7] are in fact dis-repairing tumor suppressor genes, and this is clearly associated with tumor progression and resistance to therapies."

Preclinical research has shown that cidofovir can prevent the transformation of HPV-infected cervical cells (Oncogene 2002;21:2334-46), and that it has antiangiogenic and antimetastatic activity (PLoS One 2009;4:e5018), Dr. Deutsch noted. Thus, it could be used as a potential adjunct to current therapy to improve the outcome of more than 10,800 women who are diagnosed with cervical cancer in the United States each year. In all, 24,900 HPV-related cancers occur each year in the U.S., according to Dr. Deutsch.

Cidofovir (Vistide) is an injectable antiviral drug approved for a very specific indication – the treatment of retinal inflammation due to cytomegalovirus in patients with AIDS. The fact that the drug is approved means that it is a known entity, and this could help fast-track its use if supported by suitable evidence.

On the basis of the preclinical evidence, Dr. Deutsch and his colleagues have initiated a phase I clinical trial in patients with locally advanced cervical cancer. Although cidofovir is not a new agent, a phase I trial is needed as the drug is being used in combination with the standard therapy for cervical cancer – and it’s important to show that there are no dose-limiting toxicities. According to the cidofovir package insert, patients need to be monitored closely for acute renal failure and neutropenia.

In the trial, the antiviral agent is being given once weekly and patients receive external-beam pelvic radiotherapy (45 Gy in 1.8-Gy fractions) plus carboplatin, followed by brachytherapy and chemotherapy. The dose levels explored so far range up to 5 mg/kg during the full course of radiotherapy, and no dose-limiting toxicities have been observed after up to 2 years for some doses. No local failures have been reported.

Target accrual is 12 patients, and a 10-patient extension is planned to evaluate efficacy. Phase I should be complete this year, and phase II in 2011-2012.

Although these data are preliminary, they indicate that cidofovir could be a potential radiosensitizer, Dr. Deutsch said. The fact that no toxicities have been seen to date also suggests that the risk-benefit ratio could favor combining the antiviral with radiation and chemotherapy. Phase II/III studies will be needed to confirm these results.

Dr. Deutsch noted that these findings could also potentially produce a quicker solution to tackling the problem of HPV-associated cancers, as current vaccination programs will need between 1 and 2 decades’ lead time before they could have any real effect.

The study is sponsored by the Institut Gustave Roussy. Dr. Deutsch did not state any conflicts of interest.

LONDON – An antiviral agent normally used to treat an AIDS-associated complication could increase the sensitivity of cancers associated with human papillomaviruses to chemoradiotherapy, according to preliminary study findings.

As reported at the European Society for Therapeutic Radiation Oncology Anniversary Conference, cidofovir appears to increase the sensitivity of locally advanced cervical carcinomas to the effects of radiotherapy and chemotherapy. It has resulted in no local failures or toxicities in 10 patients treated to date in an ongoing phase I dose escalation study.

Although still in very early days, the novel approach holds promise for using the antiviral agent as a possible radiosensitizer in HPV-related cancers, researchers at the Institut Gustave-Roussy in Villejuif, France, believe.

HPV infection has been associated with the development of several tumor types, including cervical, head and neck, and anal carcinoma, Dr. Eric Deutsch, a professor of radiation oncology at the institute, explained at a press briefing on May 11 .

"We know a lot about the underlying molecular mechanisms of HPV infection," Dr. Deutsch observed. "We know that HPV oncogenes [E6 and E7] are in fact dis-repairing tumor suppressor genes, and this is clearly associated with tumor progression and resistance to therapies."

Preclinical research has shown that cidofovir can prevent the transformation of HPV-infected cervical cells (Oncogene 2002;21:2334-46), and that it has antiangiogenic and antimetastatic activity (PLoS One 2009;4:e5018), Dr. Deutsch noted. Thus, it could be used as a potential adjunct to current therapy to improve the outcome of more than 10,800 women who are diagnosed with cervical cancer in the United States each year. In all, 24,900 HPV-related cancers occur each year in the U.S., according to Dr. Deutsch.

Cidofovir (Vistide) is an injectable antiviral drug approved for a very specific indication – the treatment of retinal inflammation due to cytomegalovirus in patients with AIDS. The fact that the drug is approved means that it is a known entity, and this could help fast-track its use if supported by suitable evidence.

On the basis of the preclinical evidence, Dr. Deutsch and his colleagues have initiated a phase I clinical trial in patients with locally advanced cervical cancer. Although cidofovir is not a new agent, a phase I trial is needed as the drug is being used in combination with the standard therapy for cervical cancer – and it’s important to show that there are no dose-limiting toxicities. According to the cidofovir package insert, patients need to be monitored closely for acute renal failure and neutropenia.

In the trial, the antiviral agent is being given once weekly and patients receive external-beam pelvic radiotherapy (45 Gy in 1.8-Gy fractions) plus carboplatin, followed by brachytherapy and chemotherapy. The dose levels explored so far range up to 5 mg/kg during the full course of radiotherapy, and no dose-limiting toxicities have been observed after up to 2 years for some doses. No local failures have been reported.

Target accrual is 12 patients, and a 10-patient extension is planned to evaluate efficacy. Phase I should be complete this year, and phase II in 2011-2012.

Although these data are preliminary, they indicate that cidofovir could be a potential radiosensitizer, Dr. Deutsch said. The fact that no toxicities have been seen to date also suggests that the risk-benefit ratio could favor combining the antiviral with radiation and chemotherapy. Phase II/III studies will be needed to confirm these results.

Dr. Deutsch noted that these findings could also potentially produce a quicker solution to tackling the problem of HPV-associated cancers, as current vaccination programs will need between 1 and 2 decades’ lead time before they could have any real effect.

The study is sponsored by the Institut Gustave Roussy. Dr. Deutsch did not state any conflicts of interest.

LONDON – An antiviral agent normally used to treat an AIDS-associated complication could increase the sensitivity of cancers associated with human papillomaviruses to chemoradiotherapy, according to preliminary study findings.

As reported at the European Society for Therapeutic Radiation Oncology Anniversary Conference, cidofovir appears to increase the sensitivity of locally advanced cervical carcinomas to the effects of radiotherapy and chemotherapy. It has resulted in no local failures or toxicities in 10 patients treated to date in an ongoing phase I dose escalation study.

Although still in very early days, the novel approach holds promise for using the antiviral agent as a possible radiosensitizer in HPV-related cancers, researchers at the Institut Gustave-Roussy in Villejuif, France, believe.

HPV infection has been associated with the development of several tumor types, including cervical, head and neck, and anal carcinoma, Dr. Eric Deutsch, a professor of radiation oncology at the institute, explained at a press briefing on May 11 .

"We know a lot about the underlying molecular mechanisms of HPV infection," Dr. Deutsch observed. "We know that HPV oncogenes [E6 and E7] are in fact dis-repairing tumor suppressor genes, and this is clearly associated with tumor progression and resistance to therapies."

Preclinical research has shown that cidofovir can prevent the transformation of HPV-infected cervical cells (Oncogene 2002;21:2334-46), and that it has antiangiogenic and antimetastatic activity (PLoS One 2009;4:e5018), Dr. Deutsch noted. Thus, it could be used as a potential adjunct to current therapy to improve the outcome of more than 10,800 women who are diagnosed with cervical cancer in the United States each year. In all, 24,900 HPV-related cancers occur each year in the U.S., according to Dr. Deutsch.

Cidofovir (Vistide) is an injectable antiviral drug approved for a very specific indication – the treatment of retinal inflammation due to cytomegalovirus in patients with AIDS. The fact that the drug is approved means that it is a known entity, and this could help fast-track its use if supported by suitable evidence.

On the basis of the preclinical evidence, Dr. Deutsch and his colleagues have initiated a phase I clinical trial in patients with locally advanced cervical cancer. Although cidofovir is not a new agent, a phase I trial is needed as the drug is being used in combination with the standard therapy for cervical cancer – and it’s important to show that there are no dose-limiting toxicities. According to the cidofovir package insert, patients need to be monitored closely for acute renal failure and neutropenia.

In the trial, the antiviral agent is being given once weekly and patients receive external-beam pelvic radiotherapy (45 Gy in 1.8-Gy fractions) plus carboplatin, followed by brachytherapy and chemotherapy. The dose levels explored so far range up to 5 mg/kg during the full course of radiotherapy, and no dose-limiting toxicities have been observed after up to 2 years for some doses. No local failures have been reported.

Target accrual is 12 patients, and a 10-patient extension is planned to evaluate efficacy. Phase I should be complete this year, and phase II in 2011-2012.

Although these data are preliminary, they indicate that cidofovir could be a potential radiosensitizer, Dr. Deutsch said. The fact that no toxicities have been seen to date also suggests that the risk-benefit ratio could favor combining the antiviral with radiation and chemotherapy. Phase II/III studies will be needed to confirm these results.

Dr. Deutsch noted that these findings could also potentially produce a quicker solution to tackling the problem of HPV-associated cancers, as current vaccination programs will need between 1 and 2 decades’ lead time before they could have any real effect.

The study is sponsored by the Institut Gustave Roussy. Dr. Deutsch did not state any conflicts of interest.

LONDON – Despite some benefits, most notably the reduction of hot flashes, intermittent androgen suppression did not greatly improve quality of life in a large phase III study that compared the approach vs. continuous androgen deprivation in men with prostate cancer.

"The bottom line so far from the primary quality of life analysis and the primary end points of this randomized trial of over 1,300 patients is that the overall survival is equivalent whether you use continuous or intermittent androgen suppression for relapse," said Dr. Graeme G. Duncan, an investigator from the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG)–led PR.7 study.

Dr. Duncan, a radiation oncologist at the British Columbia Cancer Agency’s Vancouver Centre and the University of British Columbia in Vancouver, reported the quality of life (QOL) findings May 11 at the European Society for Therapeutic Radiation Oncology Anniversary Conference.

In all, 690 patients had been treated with intermittent androgen suppression (IAS) and 696 with continuous androgen deprivation. Dr. Duncan noted that almost all patients had received radiotherapy before randomization. The median age of patients in the trial was 74 years in both treatment arms. QOL assessments were made every 4 months for the first 2 years, and then every 8 months and at the castration resistance.

The noninferiority trial was stopped early at a median follow up of 6.9 years, as IAS was found to be as good as continuous androgen deprivation in terms of achieving the primary end point of median overall survival (8.8 years with IAS vs. 9.1 years; hazard ratio, 1.02; P = .009).

"Over 800 patients were alive when we closed the study," Dr. Duncan said, noting that this was a rather surprising finding. Of 524 patients for whom the cause of death was known, 37% had died of prostate cancer, 22% had another primary tumor, and 32% died from other causes. The top five adverse events reported were hot flashes, erectile dysfunction, libido changes, urinary frequency, and fatigue.

Dr. Duncan noted that the NCIC has a standard way of assessing QOL – a 100-point scale – and that an improvement of greater than 10 points had been shown to be clinically significant. With this method, response can be categorized as improved, stable, or worse.

"The problem with this trial is the complexity, because patients are cycling in and out of treatment," Dr. Duncan observed. This means that only a single change can be measured at a particular time point, and once a change has been recoded, "that’s it."

With this in mind, however, researchers found that small benefits favored IAS over continuous androgen deprivation in terms of physical function, fatigue, urinary symptoms, hot flashes, libido changes, and sexual function.

Looking at the data over time, Dr. Duncan noted that patients who were given IAS tended to experience fatigue at a slightly lower rate than did those with continuous androgen deprivation. "There is a definite difference, but it is relatively small in terms of clinical meaningfulness for patients," Dr. Duncan said.

In contrast, the frequency of hot flashes lessened very markedly, with a 20-point difference at 2 years. After this large dip, scores worsened in the IAS group but still remained lower than in the continuous arm. "This is certainly, by far, the largest clinical gain symptomatically in quality of life for patients in this study," Dr. Duncan said.

Around 35% of patients had a recovery of their baseline testosterone levels before recommencing androgen suppression after the first treatment cycle.

"One of the other major findings of the study is that drug use is substantially reduced using the intermittent approach," Dr. Duncan said. Indeed, the use of an LHRH (luteinizing-hormone-releasing hormone) analog was cut by two-thirds in the IAS arm, with the median duration of LHRH use of 14.3 months vs. 43.9 months in the continuous androgen deprivation arm. This could result in considerable cost savings, he suggested.

"QOL is crucial, and there are definite benefits to intermittent androgen suppression," Dr. Duncan maintained. "A subset of patients we would hope to identify will definitely benefit, and maybe we can earmark those patients" for IAS, he suggested.

The NCIC Clinical Trials Group is supported by the Canadian Cancer Society. Dr. Duncan did not state any conflicts of interest.

LONDON – Despite some benefits, most notably the reduction of hot flashes, intermittent androgen suppression did not greatly improve quality of life in a large phase III study that compared the approach vs. continuous androgen deprivation in men with prostate cancer.

"The bottom line so far from the primary quality of life analysis and the primary end points of this randomized trial of over 1,300 patients is that the overall survival is equivalent whether you use continuous or intermittent androgen suppression for relapse," said Dr. Graeme G. Duncan, an investigator from the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG)–led PR.7 study.

Dr. Duncan, a radiation oncologist at the British Columbia Cancer Agency’s Vancouver Centre and the University of British Columbia in Vancouver, reported the quality of life (QOL) findings May 11 at the European Society for Therapeutic Radiation Oncology Anniversary Conference.

In all, 690 patients had been treated with intermittent androgen suppression (IAS) and 696 with continuous androgen deprivation. Dr. Duncan noted that almost all patients had received radiotherapy before randomization. The median age of patients in the trial was 74 years in both treatment arms. QOL assessments were made every 4 months for the first 2 years, and then every 8 months and at the castration resistance.

The noninferiority trial was stopped early at a median follow up of 6.9 years, as IAS was found to be as good as continuous androgen deprivation in terms of achieving the primary end point of median overall survival (8.8 years with IAS vs. 9.1 years; hazard ratio, 1.02; P = .009).

"Over 800 patients were alive when we closed the study," Dr. Duncan said, noting that this was a rather surprising finding. Of 524 patients for whom the cause of death was known, 37% had died of prostate cancer, 22% had another primary tumor, and 32% died from other causes. The top five adverse events reported were hot flashes, erectile dysfunction, libido changes, urinary frequency, and fatigue.

Dr. Duncan noted that the NCIC has a standard way of assessing QOL – a 100-point scale – and that an improvement of greater than 10 points had been shown to be clinically significant. With this method, response can be categorized as improved, stable, or worse.

"The problem with this trial is the complexity, because patients are cycling in and out of treatment," Dr. Duncan observed. This means that only a single change can be measured at a particular time point, and once a change has been recoded, "that’s it."

With this in mind, however, researchers found that small benefits favored IAS over continuous androgen deprivation in terms of physical function, fatigue, urinary symptoms, hot flashes, libido changes, and sexual function.

Looking at the data over time, Dr. Duncan noted that patients who were given IAS tended to experience fatigue at a slightly lower rate than did those with continuous androgen deprivation. "There is a definite difference, but it is relatively small in terms of clinical meaningfulness for patients," Dr. Duncan said.

In contrast, the frequency of hot flashes lessened very markedly, with a 20-point difference at 2 years. After this large dip, scores worsened in the IAS group but still remained lower than in the continuous arm. "This is certainly, by far, the largest clinical gain symptomatically in quality of life for patients in this study," Dr. Duncan said.

Around 35% of patients had a recovery of their baseline testosterone levels before recommencing androgen suppression after the first treatment cycle.

"One of the other major findings of the study is that drug use is substantially reduced using the intermittent approach," Dr. Duncan said. Indeed, the use of an LHRH (luteinizing-hormone-releasing hormone) analog was cut by two-thirds in the IAS arm, with the median duration of LHRH use of 14.3 months vs. 43.9 months in the continuous androgen deprivation arm. This could result in considerable cost savings, he suggested.

"QOL is crucial, and there are definite benefits to intermittent androgen suppression," Dr. Duncan maintained. "A subset of patients we would hope to identify will definitely benefit, and maybe we can earmark those patients" for IAS, he suggested.

The NCIC Clinical Trials Group is supported by the Canadian Cancer Society. Dr. Duncan did not state any conflicts of interest.

LONDON – Despite some benefits, most notably the reduction of hot flashes, intermittent androgen suppression did not greatly improve quality of life in a large phase III study that compared the approach vs. continuous androgen deprivation in men with prostate cancer.

"The bottom line so far from the primary quality of life analysis and the primary end points of this randomized trial of over 1,300 patients is that the overall survival is equivalent whether you use continuous or intermittent androgen suppression for relapse," said Dr. Graeme G. Duncan, an investigator from the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG)–led PR.7 study.

Dr. Duncan, a radiation oncologist at the British Columbia Cancer Agency’s Vancouver Centre and the University of British Columbia in Vancouver, reported the quality of life (QOL) findings May 11 at the European Society for Therapeutic Radiation Oncology Anniversary Conference.

In all, 690 patients had been treated with intermittent androgen suppression (IAS) and 696 with continuous androgen deprivation. Dr. Duncan noted that almost all patients had received radiotherapy before randomization. The median age of patients in the trial was 74 years in both treatment arms. QOL assessments were made every 4 months for the first 2 years, and then every 8 months and at the castration resistance.

The noninferiority trial was stopped early at a median follow up of 6.9 years, as IAS was found to be as good as continuous androgen deprivation in terms of achieving the primary end point of median overall survival (8.8 years with IAS vs. 9.1 years; hazard ratio, 1.02; P = .009).

"Over 800 patients were alive when we closed the study," Dr. Duncan said, noting that this was a rather surprising finding. Of 524 patients for whom the cause of death was known, 37% had died of prostate cancer, 22% had another primary tumor, and 32% died from other causes. The top five adverse events reported were hot flashes, erectile dysfunction, libido changes, urinary frequency, and fatigue.

Dr. Duncan noted that the NCIC has a standard way of assessing QOL – a 100-point scale – and that an improvement of greater than 10 points had been shown to be clinically significant. With this method, response can be categorized as improved, stable, or worse.

"The problem with this trial is the complexity, because patients are cycling in and out of treatment," Dr. Duncan observed. This means that only a single change can be measured at a particular time point, and once a change has been recoded, "that’s it."

With this in mind, however, researchers found that small benefits favored IAS over continuous androgen deprivation in terms of physical function, fatigue, urinary symptoms, hot flashes, libido changes, and sexual function.

Looking at the data over time, Dr. Duncan noted that patients who were given IAS tended to experience fatigue at a slightly lower rate than did those with continuous androgen deprivation. "There is a definite difference, but it is relatively small in terms of clinical meaningfulness for patients," Dr. Duncan said.

In contrast, the frequency of hot flashes lessened very markedly, with a 20-point difference at 2 years. After this large dip, scores worsened in the IAS group but still remained lower than in the continuous arm. "This is certainly, by far, the largest clinical gain symptomatically in quality of life for patients in this study," Dr. Duncan said.

Around 35% of patients had a recovery of their baseline testosterone levels before recommencing androgen suppression after the first treatment cycle.

"One of the other major findings of the study is that drug use is substantially reduced using the intermittent approach," Dr. Duncan said. Indeed, the use of an LHRH (luteinizing-hormone-releasing hormone) analog was cut by two-thirds in the IAS arm, with the median duration of LHRH use of 14.3 months vs. 43.9 months in the continuous androgen deprivation arm. This could result in considerable cost savings, he suggested.

"QOL is crucial, and there are definite benefits to intermittent androgen suppression," Dr. Duncan maintained. "A subset of patients we would hope to identify will definitely benefit, and maybe we can earmark those patients" for IAS, he suggested.

The NCIC Clinical Trials Group is supported by the Canadian Cancer Society. Dr. Duncan did not state any conflicts of interest.

LONDON – Despite some benefits, most notably the reduction of hot flashes, intermittent androgen suppression did not greatly improve quality of life in a large phase III study that compared the approach vs. continuous androgen deprivation in men with prostate cancer.

"The bottom line so far from the primary quality of life analysis and the primary end points of this randomized trial of over 1,300 patients is that the overall survival is equivalent whether you use continuous or intermittent androgen suppression for relapse," said Dr. Graeme G. Duncan, an investigator from the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG)–led PR.7 study.

Dr. Duncan, a radiation oncologist at the British Columbia Cancer Agency’s Vancouver Centre and the University of British Columbia in Vancouver, reported the quality of life (QOL) findings May 11 at the European Society for Therapeutic Radiation Oncology Anniversary Conference.

In all, 690 patients had been treated with intermittent androgen suppression (IAS) and 696 with continuous androgen deprivation. Dr. Duncan noted that almost all patients had received radiotherapy before randomization. The median age of patients in the trial was 74 years in both treatment arms. QOL assessments were made every 4 months for the first 2 years, and then every 8 months and at the castration resistance.

The noninferiority trial was stopped early at a median follow up of 6.9 years, as IAS was found to be as good as continuous androgen deprivation in terms of achieving the primary end point of median overall survival (8.8 years with IAS vs. 9.1 years; hazard ratio, 1.02; P = .009).

"Over 800 patients were alive when we closed the study," Dr. Duncan said, noting that this was a rather surprising finding. Of 524 patients for whom the cause of death was known, 37% had died of prostate cancer, 22% had another primary tumor, and 32% died from other causes. The top five adverse events reported were hot flashes, erectile dysfunction, libido changes, urinary frequency, and fatigue.

Dr. Duncan noted that the NCIC has a standard way of assessing QOL – a 100-point scale – and that an improvement of greater than 10 points had been shown to be clinically significant. With this method, response can be categorized as improved, stable, or worse.

"The problem with this trial is the complexity, because patients are cycling in and out of treatment," Dr. Duncan observed. This means that only a single change can be measured at a particular time point, and once a change has been recoded, "that’s it."

With this in mind, however, researchers found that small benefits favored IAS over continuous androgen deprivation in terms of physical function, fatigue, urinary symptoms, hot flashes, libido changes, and sexual function.

Looking at the data over time, Dr. Duncan noted that patients who were given IAS tended to experience fatigue at a slightly lower rate than did those with continuous androgen deprivation. "There is a definite difference, but it is relatively small in terms of clinical meaningfulness for patients," Dr. Duncan said.

In contrast, the frequency of hot flashes lessened very markedly, with a 20-point difference at 2 years. After this large dip, scores worsened in the IAS group but still remained lower than in the continuous arm. "This is certainly, by far, the largest clinical gain symptomatically in quality of life for patients in this study," Dr. Duncan said.

Around 35% of patients had a recovery of their baseline testosterone levels before recommencing androgen suppression after the first treatment cycle.

"One of the other major findings of the study is that drug use is substantially reduced using the intermittent approach," Dr. Duncan said. Indeed, the use of an LHRH (luteinizing-hormone-releasing hormone) analog was cut by two-thirds in the IAS arm, with the median duration of LHRH use of 14.3 months vs. 43.9 months in the continuous androgen deprivation arm. This could result in considerable cost savings, he suggested.

"QOL is crucial, and there are definite benefits to intermittent androgen suppression," Dr. Duncan maintained. "A subset of patients we would hope to identify will definitely benefit, and maybe we can earmark those patients" for IAS, he suggested.

The NCIC Clinical Trials Group is supported by the Canadian Cancer Society. Dr. Duncan did not state any conflicts of interest.

LONDON – Despite some benefits, most notably the reduction of hot flashes, intermittent androgen suppression did not greatly improve quality of life in a large phase III study that compared the approach vs. continuous androgen deprivation in men with prostate cancer.

"The bottom line so far from the primary quality of life analysis and the primary end points of this randomized trial of over 1,300 patients is that the overall survival is equivalent whether you use continuous or intermittent androgen suppression for relapse," said Dr. Graeme G. Duncan, an investigator from the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG)–led PR.7 study.

Dr. Duncan, a radiation oncologist at the British Columbia Cancer Agency’s Vancouver Centre and the University of British Columbia in Vancouver, reported the quality of life (QOL) findings May 11 at the European Society for Therapeutic Radiation Oncology Anniversary Conference.

In all, 690 patients had been treated with intermittent androgen suppression (IAS) and 696 with continuous androgen deprivation. Dr. Duncan noted that almost all patients had received radiotherapy before randomization. The median age of patients in the trial was 74 years in both treatment arms. QOL assessments were made every 4 months for the first 2 years, and then every 8 months and at the castration resistance.

The noninferiority trial was stopped early at a median follow up of 6.9 years, as IAS was found to be as good as continuous androgen deprivation in terms of achieving the primary end point of median overall survival (8.8 years with IAS vs. 9.1 years; hazard ratio, 1.02; P = .009).

"Over 800 patients were alive when we closed the study," Dr. Duncan said, noting that this was a rather surprising finding. Of 524 patients for whom the cause of death was known, 37% had died of prostate cancer, 22% had another primary tumor, and 32% died from other causes. The top five adverse events reported were hot flashes, erectile dysfunction, libido changes, urinary frequency, and fatigue.

Dr. Duncan noted that the NCIC has a standard way of assessing QOL – a 100-point scale – and that an improvement of greater than 10 points had been shown to be clinically significant. With this method, response can be categorized as improved, stable, or worse.

"The problem with this trial is the complexity, because patients are cycling in and out of treatment," Dr. Duncan observed. This means that only a single change can be measured at a particular time point, and once a change has been recoded, "that’s it."

With this in mind, however, researchers found that small benefits favored IAS over continuous androgen deprivation in terms of physical function, fatigue, urinary symptoms, hot flashes, libido changes, and sexual function.

Looking at the data over time, Dr. Duncan noted that patients who were given IAS tended to experience fatigue at a slightly lower rate than did those with continuous androgen deprivation. "There is a definite difference, but it is relatively small in terms of clinical meaningfulness for patients," Dr. Duncan said.

In contrast, the frequency of hot flashes lessened very markedly, with a 20-point difference at 2 years. After this large dip, scores worsened in the IAS group but still remained lower than in the continuous arm. "This is certainly, by far, the largest clinical gain symptomatically in quality of life for patients in this study," Dr. Duncan said.

Around 35% of patients had a recovery of their baseline testosterone levels before recommencing androgen suppression after the first treatment cycle.

"One of the other major findings of the study is that drug use is substantially reduced using the intermittent approach," Dr. Duncan said. Indeed, the use of an LHRH (luteinizing-hormone-releasing hormone) analog was cut by two-thirds in the IAS arm, with the median duration of LHRH use of 14.3 months vs. 43.9 months in the continuous androgen deprivation arm. This could result in considerable cost savings, he suggested.

"QOL is crucial, and there are definite benefits to intermittent androgen suppression," Dr. Duncan maintained. "A subset of patients we would hope to identify will definitely benefit, and maybe we can earmark those patients" for IAS, he suggested.

The NCIC Clinical Trials Group is supported by the Canadian Cancer Society. Dr. Duncan did not state any conflicts of interest.

LONDON – Despite some benefits, most notably the reduction of hot flashes, intermittent androgen suppression did not greatly improve quality of life in a large phase III study that compared the approach vs. continuous androgen deprivation in men with prostate cancer.

"The bottom line so far from the primary quality of life analysis and the primary end points of this randomized trial of over 1,300 patients is that the overall survival is equivalent whether you use continuous or intermittent androgen suppression for relapse," said Dr. Graeme G. Duncan, an investigator from the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG)–led PR.7 study.

Dr. Duncan, a radiation oncologist at the British Columbia Cancer Agency’s Vancouver Centre and the University of British Columbia in Vancouver, reported the quality of life (QOL) findings May 11 at the European Society for Therapeutic Radiation Oncology Anniversary Conference.

In all, 690 patients had been treated with intermittent androgen suppression (IAS) and 696 with continuous androgen deprivation. Dr. Duncan noted that almost all patients had received radiotherapy before randomization. The median age of patients in the trial was 74 years in both treatment arms. QOL assessments were made every 4 months for the first 2 years, and then every 8 months and at the castration resistance.

The noninferiority trial was stopped early at a median follow up of 6.9 years, as IAS was found to be as good as continuous androgen deprivation in terms of achieving the primary end point of median overall survival (8.8 years with IAS vs. 9.1 years; hazard ratio, 1.02; P = .009).

"Over 800 patients were alive when we closed the study," Dr. Duncan said, noting that this was a rather surprising finding. Of 524 patients for whom the cause of death was known, 37% had died of prostate cancer, 22% had another primary tumor, and 32% died from other causes. The top five adverse events reported were hot flashes, erectile dysfunction, libido changes, urinary frequency, and fatigue.

Dr. Duncan noted that the NCIC has a standard way of assessing QOL – a 100-point scale – and that an improvement of greater than 10 points had been shown to be clinically significant. With this method, response can be categorized as improved, stable, or worse.

"The problem with this trial is the complexity, because patients are cycling in and out of treatment," Dr. Duncan observed. This means that only a single change can be measured at a particular time point, and once a change has been recoded, "that’s it."

With this in mind, however, researchers found that small benefits favored IAS over continuous androgen deprivation in terms of physical function, fatigue, urinary symptoms, hot flashes, libido changes, and sexual function.

Looking at the data over time, Dr. Duncan noted that patients who were given IAS tended to experience fatigue at a slightly lower rate than did those with continuous androgen deprivation. "There is a definite difference, but it is relatively small in terms of clinical meaningfulness for patients," Dr. Duncan said.

In contrast, the frequency of hot flashes lessened very markedly, with a 20-point difference at 2 years. After this large dip, scores worsened in the IAS group but still remained lower than in the continuous arm. "This is certainly, by far, the largest clinical gain symptomatically in quality of life for patients in this study," Dr. Duncan said.

Around 35% of patients had a recovery of their baseline testosterone levels before recommencing androgen suppression after the first treatment cycle.

"One of the other major findings of the study is that drug use is substantially reduced using the intermittent approach," Dr. Duncan said. Indeed, the use of an LHRH (luteinizing-hormone-releasing hormone) analog was cut by two-thirds in the IAS arm, with the median duration of LHRH use of 14.3 months vs. 43.9 months in the continuous androgen deprivation arm. This could result in considerable cost savings, he suggested.

"QOL is crucial, and there are definite benefits to intermittent androgen suppression," Dr. Duncan maintained. "A subset of patients we would hope to identify will definitely benefit, and maybe we can earmark those patients" for IAS, he suggested.

The NCIC Clinical Trials Group is supported by the Canadian Cancer Society. Dr. Duncan did not state any conflicts of interest.

LONDON – Despite some benefits, most notably the reduction of hot flashes, intermittent androgen suppression did not greatly improve quality of life in a large phase III study that compared the approach vs. continuous androgen deprivation in men with prostate cancer.

"The bottom line so far from the primary quality of life analysis and the primary end points of this randomized trial of over 1,300 patients is that the overall survival is equivalent whether you use continuous or intermittent androgen suppression for relapse," said Dr. Graeme G. Duncan, an investigator from the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG)–led PR.7 study.

Dr. Duncan, a radiation oncologist at the British Columbia Cancer Agency’s Vancouver Centre and the University of British Columbia in Vancouver, reported the quality of life (QOL) findings May 11 at the European Society for Therapeutic Radiation Oncology Anniversary Conference.

In all, 690 patients had been treated with intermittent androgen suppression (IAS) and 696 with continuous androgen deprivation. Dr. Duncan noted that almost all patients had received radiotherapy before randomization. The median age of patients in the trial was 74 years in both treatment arms. QOL assessments were made every 4 months for the first 2 years, and then every 8 months and at the castration resistance.

The noninferiority trial was stopped early at a median follow up of 6.9 years, as IAS was found to be as good as continuous androgen deprivation in terms of achieving the primary end point of median overall survival (8.8 years with IAS vs. 9.1 years; hazard ratio, 1.02; P = .009).

"Over 800 patients were alive when we closed the study," Dr. Duncan said, noting that this was a rather surprising finding. Of 524 patients for whom the cause of death was known, 37% had died of prostate cancer, 22% had another primary tumor, and 32% died from other causes. The top five adverse events reported were hot flashes, erectile dysfunction, libido changes, urinary frequency, and fatigue.

Dr. Duncan noted that the NCIC has a standard way of assessing QOL – a 100-point scale – and that an improvement of greater than 10 points had been shown to be clinically significant. With this method, response can be categorized as improved, stable, or worse.

"The problem with this trial is the complexity, because patients are cycling in and out of treatment," Dr. Duncan observed. This means that only a single change can be measured at a particular time point, and once a change has been recoded, "that’s it."

With this in mind, however, researchers found that small benefits favored IAS over continuous androgen deprivation in terms of physical function, fatigue, urinary symptoms, hot flashes, libido changes, and sexual function.

Looking at the data over time, Dr. Duncan noted that patients who were given IAS tended to experience fatigue at a slightly lower rate than did those with continuous androgen deprivation. "There is a definite difference, but it is relatively small in terms of clinical meaningfulness for patients," Dr. Duncan said.

In contrast, the frequency of hot flashes lessened very markedly, with a 20-point difference at 2 years. After this large dip, scores worsened in the IAS group but still remained lower than in the continuous arm. "This is certainly, by far, the largest clinical gain symptomatically in quality of life for patients in this study," Dr. Duncan said.

Around 35% of patients had a recovery of their baseline testosterone levels before recommencing androgen suppression after the first treatment cycle.

"One of the other major findings of the study is that drug use is substantially reduced using the intermittent approach," Dr. Duncan said. Indeed, the use of an LHRH (luteinizing-hormone-releasing hormone) analog was cut by two-thirds in the IAS arm, with the median duration of LHRH use of 14.3 months vs. 43.9 months in the continuous androgen deprivation arm. This could result in considerable cost savings, he suggested.

"QOL is crucial, and there are definite benefits to intermittent androgen suppression," Dr. Duncan maintained. "A subset of patients we would hope to identify will definitely benefit, and maybe we can earmark those patients" for IAS, he suggested.

The NCIC Clinical Trials Group is supported by the Canadian Cancer Society. Dr. Duncan did not state any conflicts of interest.

LONDON – Despite some benefits, most notably the reduction of hot flashes, intermittent androgen suppression did not greatly improve quality of life in a large phase III study that compared the approach vs. continuous androgen deprivation in men with prostate cancer.

"The bottom line so far from the primary quality of life analysis and the primary end points of this randomized trial of over 1,300 patients is that the overall survival is equivalent whether you use continuous or intermittent androgen suppression for relapse," said Dr. Graeme G. Duncan, an investigator from the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG)–led PR.7 study.

Dr. Duncan, a radiation oncologist at the British Columbia Cancer Agency’s Vancouver Centre and the University of British Columbia in Vancouver, reported the quality of life (QOL) findings May 11 at the European Society for Therapeutic Radiation Oncology Anniversary Conference.

In all, 690 patients had been treated with intermittent androgen suppression (IAS) and 696 with continuous androgen deprivation. Dr. Duncan noted that almost all patients had received radiotherapy before randomization. The median age of patients in the trial was 74 years in both treatment arms. QOL assessments were made every 4 months for the first 2 years, and then every 8 months and at the castration resistance.

The noninferiority trial was stopped early at a median follow up of 6.9 years, as IAS was found to be as good as continuous androgen deprivation in terms of achieving the primary end point of median overall survival (8.8 years with IAS vs. 9.1 years; hazard ratio, 1.02; P = .009).

"Over 800 patients were alive when we closed the study," Dr. Duncan said, noting that this was a rather surprising finding. Of 524 patients for whom the cause of death was known, 37% had died of prostate cancer, 22% had another primary tumor, and 32% died from other causes. The top five adverse events reported were hot flashes, erectile dysfunction, libido changes, urinary frequency, and fatigue.

Dr. Duncan noted that the NCIC has a standard way of assessing QOL – a 100-point scale – and that an improvement of greater than 10 points had been shown to be clinically significant. With this method, response can be categorized as improved, stable, or worse.

"The problem with this trial is the complexity, because patients are cycling in and out of treatment," Dr. Duncan observed. This means that only a single change can be measured at a particular time point, and once a change has been recoded, "that’s it."

With this in mind, however, researchers found that small benefits favored IAS over continuous androgen deprivation in terms of physical function, fatigue, urinary symptoms, hot flashes, libido changes, and sexual function.

Looking at the data over time, Dr. Duncan noted that patients who were given IAS tended to experience fatigue at a slightly lower rate than did those with continuous androgen deprivation. "There is a definite difference, but it is relatively small in terms of clinical meaningfulness for patients," Dr. Duncan said.

In contrast, the frequency of hot flashes lessened very markedly, with a 20-point difference at 2 years. After this large dip, scores worsened in the IAS group but still remained lower than in the continuous arm. "This is certainly, by far, the largest clinical gain symptomatically in quality of life for patients in this study," Dr. Duncan said.

Around 35% of patients had a recovery of their baseline testosterone levels before recommencing androgen suppression after the first treatment cycle.

"One of the other major findings of the study is that drug use is substantially reduced using the intermittent approach," Dr. Duncan said. Indeed, the use of an LHRH (luteinizing-hormone-releasing hormone) analog was cut by two-thirds in the IAS arm, with the median duration of LHRH use of 14.3 months vs. 43.9 months in the continuous androgen deprivation arm. This could result in considerable cost savings, he suggested.

"QOL is crucial, and there are definite benefits to intermittent androgen suppression," Dr. Duncan maintained. "A subset of patients we would hope to identify will definitely benefit, and maybe we can earmark those patients" for IAS, he suggested.

The NCIC Clinical Trials Group is supported by the Canadian Cancer Society. Dr. Duncan did not state any conflicts of interest.

LONDON – Despite some benefits, most notably the reduction of hot flashes, intermittent androgen suppression did not greatly improve quality of life in a large phase III study that compared the approach vs. continuous androgen deprivation in men with prostate cancer.

"The bottom line so far from the primary quality of life analysis and the primary end points of this randomized trial of over 1,300 patients is that the overall survival is equivalent whether you use continuous or intermittent androgen suppression for relapse," said Dr. Graeme G. Duncan, an investigator from the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG)–led PR.7 study.

Dr. Duncan, a radiation oncologist at the British Columbia Cancer Agency’s Vancouver Centre and the University of British Columbia in Vancouver, reported the quality of life (QOL) findings May 11 at the European Society for Therapeutic Radiation Oncology Anniversary Conference.

In all, 690 patients had been treated with intermittent androgen suppression (IAS) and 696 with continuous androgen deprivation. Dr. Duncan noted that almost all patients had received radiotherapy before randomization. The median age of patients in the trial was 74 years in both treatment arms. QOL assessments were made every 4 months for the first 2 years, and then every 8 months and at the castration resistance.

The noninferiority trial was stopped early at a median follow up of 6.9 years, as IAS was found to be as good as continuous androgen deprivation in terms of achieving the primary end point of median overall survival (8.8 years with IAS vs. 9.1 years; hazard ratio, 1.02; P = .009).

"Over 800 patients were alive when we closed the study," Dr. Duncan said, noting that this was a rather surprising finding. Of 524 patients for whom the cause of death was known, 37% had died of prostate cancer, 22% had another primary tumor, and 32% died from other causes. The top five adverse events reported were hot flashes, erectile dysfunction, libido changes, urinary frequency, and fatigue.

Dr. Duncan noted that the NCIC has a standard way of assessing QOL – a 100-point scale – and that an improvement of greater than 10 points had been shown to be clinically significant. With this method, response can be categorized as improved, stable, or worse.

"The problem with this trial is the complexity, because patients are cycling in and out of treatment," Dr. Duncan observed. This means that only a single change can be measured at a particular time point, and once a change has been recoded, "that’s it."

With this in mind, however, researchers found that small benefits favored IAS over continuous androgen deprivation in terms of physical function, fatigue, urinary symptoms, hot flashes, libido changes, and sexual function.

Looking at the data over time, Dr. Duncan noted that patients who were given IAS tended to experience fatigue at a slightly lower rate than did those with continuous androgen deprivation. "There is a definite difference, but it is relatively small in terms of clinical meaningfulness for patients," Dr. Duncan said.

In contrast, the frequency of hot flashes lessened very markedly, with a 20-point difference at 2 years. After this large dip, scores worsened in the IAS group but still remained lower than in the continuous arm. "This is certainly, by far, the largest clinical gain symptomatically in quality of life for patients in this study," Dr. Duncan said.

Around 35% of patients had a recovery of their baseline testosterone levels before recommencing androgen suppression after the first treatment cycle.

"One of the other major findings of the study is that drug use is substantially reduced using the intermittent approach," Dr. Duncan said. Indeed, the use of an LHRH (luteinizing-hormone-releasing hormone) analog was cut by two-thirds in the IAS arm, with the median duration of LHRH use of 14.3 months vs. 43.9 months in the continuous androgen deprivation arm. This could result in considerable cost savings, he suggested.

"QOL is crucial, and there are definite benefits to intermittent androgen suppression," Dr. Duncan maintained. "A subset of patients we would hope to identify will definitely benefit, and maybe we can earmark those patients" for IAS, he suggested.

The NCIC Clinical Trials Group is supported by the Canadian Cancer Society. Dr. Duncan did not state any conflicts of interest.

LONDON – Expression of the epidermal growth factor receptor predicts whether patients with laryngeal cancer will benefit from hypoxia modification in addition to accelerated radiotherapy.

Study findings reported May 9 at the European Society for Therapeutic Radiation Oncology (ESTRO) Anniversary Conference showed that low expression was associated with higher disease-specific survival and locoregional control than was high expression in patients who received ARCON (accelerated radiotherapy with carbogen and nicotinamide).

EGFR expression is prognostic for patients who are treated with conventional fractionated radiotherapy, but did not predict response in patients undergoing just AR (accelerated radiotherapy) without hypoxia modification.

"EGFR can activate different downstream signaling pathways [in the tumor cell] that – once activated – can influence tumor cell survival, proliferation, [and] migration," all of which can contribute to tumor progression, said Monique Nijkamp, a Ph.D. student in the radiation oncology department of St. Radboud University Medical Centre in Nijmegen, the Netherlands.

High expression has already been linked to worse outcome in patients who were treated with radiotherapy for head and neck cancer (Cancer Res. 2002;62:7350-6). Ms. Nijkamp said that EGFR could be activated by ionizing radiation, and could account for resistance to radiotherapy in some treated individuals.

Hypothesizing that ARCON may help to overcome this resistance, Ms. Nikamp and coworkers examined 272 biopsy samples taken from 345 patients who had been treated with accelerated radiotherapy, with or without hypoxia modification, in a phase III study.

Preliminary results of the study were reported last September at the ESTRO 29 meeting in Barcelona. They showed that ARCON significantly improved regional – but not locoregional – tumor control, compared with AR alone. All of the patients in the trial had advanced-stage laryngeal cancer.

The latest findings suggest that patients with high expression may not gain any extra benefit from the addition of hypoxia modification. Indeed, although not statistically significant, better 5-year locoregional control (88% vs. 71%) and disease-specific survival (91% vs. 78%) were seen in patients with low EGFR expression than in those with high EGFR expression who were treated with ARCON.

Ms. Nijkamp suggested that perhaps high EGFR–expressing tumors were rapidly activating downstream signaling pathways that negated the effects of hypoxia modification. No difference in outcomes was found according to EGFR expression in the AR alone arm.

"There is concern over the methodologies used to measure EGFR, and this could have a large bearing on what conclusions can be drawn from studies," said Dr. Nick Slevin, who was invited to comment on the findings.

"From the literature and from this study, it appears that high EGFR laryngeal cancers benefit from accelerated radiotherapy, but that low EGFR tumors do not," added Dr. Slevin, a consultant clinical oncologist at the Christie NHS Foundation Trust and the University of Manchester (England).

"I think it’s a fair summary to also say that high-EGFR tumors benefit from AR but not from CON [carbogen and nicotinamide] and that low-EGFR tumors benefit from the CON but not the AR. ... So I’m not sure ARCON is the right approach for all tumors."

Other approaches to hypoxia modification for low EGFR–expressing tumors (such as oral nimorazole) may overcome the logistic difficulties of delivering carbogen and nicotinamide, he added.

The study was supported by the Dutch Cancer Society. Ms. Nijkamp and Dr. Slevin declared they had no financial conflicts of interest.

LONDON – Expression of the epidermal growth factor receptor predicts whether patients with laryngeal cancer will benefit from hypoxia modification in addition to accelerated radiotherapy.

Study findings reported May 9 at the European Society for Therapeutic Radiation Oncology (ESTRO) Anniversary Conference showed that low expression was associated with higher disease-specific survival and locoregional control than was high expression in patients who received ARCON (accelerated radiotherapy with carbogen and nicotinamide).

EGFR expression is prognostic for patients who are treated with conventional fractionated radiotherapy, but did not predict response in patients undergoing just AR (accelerated radiotherapy) without hypoxia modification.

"EGFR can activate different downstream signaling pathways [in the tumor cell] that – once activated – can influence tumor cell survival, proliferation, [and] migration," all of which can contribute to tumor progression, said Monique Nijkamp, a Ph.D. student in the radiation oncology department of St. Radboud University Medical Centre in Nijmegen, the Netherlands.

High expression has already been linked to worse outcome in patients who were treated with radiotherapy for head and neck cancer (Cancer Res. 2002;62:7350-6). Ms. Nijkamp said that EGFR could be activated by ionizing radiation, and could account for resistance to radiotherapy in some treated individuals.

Hypothesizing that ARCON may help to overcome this resistance, Ms. Nikamp and coworkers examined 272 biopsy samples taken from 345 patients who had been treated with accelerated radiotherapy, with or without hypoxia modification, in a phase III study.

Preliminary results of the study were reported last September at the ESTRO 29 meeting in Barcelona. They showed that ARCON significantly improved regional – but not locoregional – tumor control, compared with AR alone. All of the patients in the trial had advanced-stage laryngeal cancer.

The latest findings suggest that patients with high expression may not gain any extra benefit from the addition of hypoxia modification. Indeed, although not statistically significant, better 5-year locoregional control (88% vs. 71%) and disease-specific survival (91% vs. 78%) were seen in patients with low EGFR expression than in those with high EGFR expression who were treated with ARCON.

Ms. Nijkamp suggested that perhaps high EGFR–expressing tumors were rapidly activating downstream signaling pathways that negated the effects of hypoxia modification. No difference in outcomes was found according to EGFR expression in the AR alone arm.

"There is concern over the methodologies used to measure EGFR, and this could have a large bearing on what conclusions can be drawn from studies," said Dr. Nick Slevin, who was invited to comment on the findings.

"From the literature and from this study, it appears that high EGFR laryngeal cancers benefit from accelerated radiotherapy, but that low EGFR tumors do not," added Dr. Slevin, a consultant clinical oncologist at the Christie NHS Foundation Trust and the University of Manchester (England).

"I think it’s a fair summary to also say that high-EGFR tumors benefit from AR but not from CON [carbogen and nicotinamide] and that low-EGFR tumors benefit from the CON but not the AR. ... So I’m not sure ARCON is the right approach for all tumors."

Other approaches to hypoxia modification for low EGFR–expressing tumors (such as oral nimorazole) may overcome the logistic difficulties of delivering carbogen and nicotinamide, he added.

The study was supported by the Dutch Cancer Society. Ms. Nijkamp and Dr. Slevin declared they had no financial conflicts of interest.

LONDON – Expression of the epidermal growth factor receptor predicts whether patients with laryngeal cancer will benefit from hypoxia modification in addition to accelerated radiotherapy.

Study findings reported May 9 at the European Society for Therapeutic Radiation Oncology (ESTRO) Anniversary Conference showed that low expression was associated with higher disease-specific survival and locoregional control than was high expression in patients who received ARCON (accelerated radiotherapy with carbogen and nicotinamide).

EGFR expression is prognostic for patients who are treated with conventional fractionated radiotherapy, but did not predict response in patients undergoing just AR (accelerated radiotherapy) without hypoxia modification.

"EGFR can activate different downstream signaling pathways [in the tumor cell] that – once activated – can influence tumor cell survival, proliferation, [and] migration," all of which can contribute to tumor progression, said Monique Nijkamp, a Ph.D. student in the radiation oncology department of St. Radboud University Medical Centre in Nijmegen, the Netherlands.

High expression has already been linked to worse outcome in patients who were treated with radiotherapy for head and neck cancer (Cancer Res. 2002;62:7350-6). Ms. Nijkamp said that EGFR could be activated by ionizing radiation, and could account for resistance to radiotherapy in some treated individuals.

Hypothesizing that ARCON may help to overcome this resistance, Ms. Nikamp and coworkers examined 272 biopsy samples taken from 345 patients who had been treated with accelerated radiotherapy, with or without hypoxia modification, in a phase III study.

Preliminary results of the study were reported last September at the ESTRO 29 meeting in Barcelona. They showed that ARCON significantly improved regional – but not locoregional – tumor control, compared with AR alone. All of the patients in the trial had advanced-stage laryngeal cancer.

The latest findings suggest that patients with high expression may not gain any extra benefit from the addition of hypoxia modification. Indeed, although not statistically significant, better 5-year locoregional control (88% vs. 71%) and disease-specific survival (91% vs. 78%) were seen in patients with low EGFR expression than in those with high EGFR expression who were treated with ARCON.

Ms. Nijkamp suggested that perhaps high EGFR–expressing tumors were rapidly activating downstream signaling pathways that negated the effects of hypoxia modification. No difference in outcomes was found according to EGFR expression in the AR alone arm.

"There is concern over the methodologies used to measure EGFR, and this could have a large bearing on what conclusions can be drawn from studies," said Dr. Nick Slevin, who was invited to comment on the findings.

"From the literature and from this study, it appears that high EGFR laryngeal cancers benefit from accelerated radiotherapy, but that low EGFR tumors do not," added Dr. Slevin, a consultant clinical oncologist at the Christie NHS Foundation Trust and the University of Manchester (England).

"I think it’s a fair summary to also say that high-EGFR tumors benefit from AR but not from CON [carbogen and nicotinamide] and that low-EGFR tumors benefit from the CON but not the AR. ... So I’m not sure ARCON is the right approach for all tumors."

Other approaches to hypoxia modification for low EGFR–expressing tumors (such as oral nimorazole) may overcome the logistic difficulties of delivering carbogen and nicotinamide, he added.

The study was supported by the Dutch Cancer Society. Ms. Nijkamp and Dr. Slevin declared they had no financial conflicts of interest.

LONDON – Low-dose irradiation of the stomach in patients with gastric MALT lymphoma absent or independent of infection by Helicobacter pylori is associated with a 93% disease control rate after 10 years.

As presented by Dr. Joachim Yahalom, a radiation oncologist at Memorial Sloan-Kettering Cancer Center in New York, these long-term study findings highlight the high disease-control rates that can be obtained using low-dose involved field radiotherapy (IFRT).

Low-dose IFRT has now become a standard of care in the United States, although approaches still vary in Europe, he reported May 9 at the European Society for Therapeutic Radiation Oncology Anniversary Conference.

Indeed, the latest guidelines set by the National Comprehensive Cancer Network on non-Hodgkin’s lymphomas – which includes gastric MALT (mucosa-associated lymphoid tissue) lymphoma of the stomach – recommend the use of radiotherapy as a first-line option when patients have early (stage I/II) H. pylori–negative disease.

"We started using this [low-dose irradiation] treatment approach in the early 90s. Until then, the standard treatment for this lymphoma in the stomach was total gastrectomy, and sometimes it was followed by radiation therapy," said Dr. Yahalom, a professor of radiation oncology at Cornell University in New York. He added that chemotherapy and rituximab (Rituxan) were not generally very effective.

"Obviously the treatment of choice is to give antibiotics if H. pylori is present," Dr. Yahalom added, noting that substantial regression of MALT lymphoma can occur via treatment with antibiotics that target the gastric bacterium in positive cases. However, when H. pylori is not present, or if there is a lack of response to or residual lymphoma after complete response to antibiotic therapy, then radiotherapy is the recommended next step.

Dr. Yahalom presented data representing 16 years of experience in treating 103 patients (60 women and 43 men) with gastric MALT lymphoma in 1992-2009. The majority of patients (76%) had stage I disease, with 19% having stage II, and fewer than 5% having stage IV.

The median age of the patients was 62 years (range, 25-91 years). Symptoms were relatively mild at presentation, Dr. Yahalom observed: In all, 52% had epigastric pain, 36% had nausea, 29% had gastric bleeding, 18% had anorexia, 15% had anemia, and 10% had unknown or no obvious symptoms.

Almost two-thirds of patients were H. pylori negative. This included four patients who had relapsed after a complete response to antibiotic therapy. A further 20% of patients had persistent lymphoma after H. pylori eradication therapy. Another 15% had H. pylori and lymphoma remaining after antibiotic treatment, but had progressive symptoms or disease that could not wait for another antibiotics trial.

Prior to being treated with IFRT, six patients had undergone surgery, and seven had received medications that failed to control their disease.

Approximately 90% of patients were given IFRT at a median dose of 30 Gy in 1.5 Gy fractions for 4 weeks. The lowest and highest total radiation doses administered were 22.5 Gy and 43.5 Gy.

Patients received regular follow up via endoscopic biopsies, and after a median of 5.5 years, the disease control rate was 98%. One-fifth of patients had been followed for 10 years, and the 10-year freedom from local failure was 93%; the 10-year overall survival rate was 74%.

There were no significant acute or late adverse events, Dr. Yahalom noted, and just eight patients relapsed (six with gastric MALT lymphoma and two with diffuse large B-cell lymphoma). Subsequent other cancers included lymphoma in extragastric sites (eight patients), adenocarcinoma of the stomach (two), and second tumors close to the radiotherapy field (one in the colon and two in the pancreas). "Other deaths appeared unrelated to disease or treatment," he said.

Based on this experience, Dr. Yahalom concluded that "low-dose irradiation of the stomach provides excellent long-term disease control [and] is safe and simple.

"Radiation therapy, in our opinion, is the treatment of choice for patients with MALT lymphoma that have exhausted their antibiotic options or are unlikely to respond to it."

Dr. Yahalom said he had no financial conflicts of interest.

LONDON – Low-dose irradiation of the stomach in patients with gastric MALT lymphoma absent or independent of infection by Helicobacter pylori is associated with a 93% disease control rate after 10 years.

As presented by Dr. Joachim Yahalom, a radiation oncologist at Memorial Sloan-Kettering Cancer Center in New York, these long-term study findings highlight the high disease-control rates that can be obtained using low-dose involved field radiotherapy (IFRT).

Low-dose IFRT has now become a standard of care in the United States, although approaches still vary in Europe, he reported May 9 at the European Society for Therapeutic Radiation Oncology Anniversary Conference.

Indeed, the latest guidelines set by the National Comprehensive Cancer Network on non-Hodgkin’s lymphomas – which includes gastric MALT (mucosa-associated lymphoid tissue) lymphoma of the stomach – recommend the use of radiotherapy as a first-line option when patients have early (stage I/II) H. pylori–negative disease.

"We started using this [low-dose irradiation] treatment approach in the early 90s. Until then, the standard treatment for this lymphoma in the stomach was total gastrectomy, and sometimes it was followed by radiation therapy," said Dr. Yahalom, a professor of radiation oncology at Cornell University in New York. He added that chemotherapy and rituximab (Rituxan) were not generally very effective.

"Obviously the treatment of choice is to give antibiotics if H. pylori is present," Dr. Yahalom added, noting that substantial regression of MALT lymphoma can occur via treatment with antibiotics that target the gastric bacterium in positive cases. However, when H. pylori is not present, or if there is a lack of response to or residual lymphoma after complete response to antibiotic therapy, then radiotherapy is the recommended next step.

Dr. Yahalom presented data representing 16 years of experience in treating 103 patients (60 women and 43 men) with gastric MALT lymphoma in 1992-2009. The majority of patients (76%) had stage I disease, with 19% having stage II, and fewer than 5% having stage IV.

The median age of the patients was 62 years (range, 25-91 years). Symptoms were relatively mild at presentation, Dr. Yahalom observed: In all, 52% had epigastric pain, 36% had nausea, 29% had gastric bleeding, 18% had anorexia, 15% had anemia, and 10% had unknown or no obvious symptoms.

Almost two-thirds of patients were H. pylori negative. This included four patients who had relapsed after a complete response to antibiotic therapy. A further 20% of patients had persistent lymphoma after H. pylori eradication therapy. Another 15% had H. pylori and lymphoma remaining after antibiotic treatment, but had progressive symptoms or disease that could not wait for another antibiotics trial.

Prior to being treated with IFRT, six patients had undergone surgery, and seven had received medications that failed to control their disease.

Approximately 90% of patients were given IFRT at a median dose of 30 Gy in 1.5 Gy fractions for 4 weeks. The lowest and highest total radiation doses administered were 22.5 Gy and 43.5 Gy.

Patients received regular follow up via endoscopic biopsies, and after a median of 5.5 years, the disease control rate was 98%. One-fifth of patients had been followed for 10 years, and the 10-year freedom from local failure was 93%; the 10-year overall survival rate was 74%.

There were no significant acute or late adverse events, Dr. Yahalom noted, and just eight patients relapsed (six with gastric MALT lymphoma and two with diffuse large B-cell lymphoma). Subsequent other cancers included lymphoma in extragastric sites (eight patients), adenocarcinoma of the stomach (two), and second tumors close to the radiotherapy field (one in the colon and two in the pancreas). "Other deaths appeared unrelated to disease or treatment," he said.

Based on this experience, Dr. Yahalom concluded that "low-dose irradiation of the stomach provides excellent long-term disease control [and] is safe and simple.

"Radiation therapy, in our opinion, is the treatment of choice for patients with MALT lymphoma that have exhausted their antibiotic options or are unlikely to respond to it."

Dr. Yahalom said he had no financial conflicts of interest.

LONDON – Low-dose irradiation of the stomach in patients with gastric MALT lymphoma absent or independent of infection by Helicobacter pylori is associated with a 93% disease control rate after 10 years.

As presented by Dr. Joachim Yahalom, a radiation oncologist at Memorial Sloan-Kettering Cancer Center in New York, these long-term study findings highlight the high disease-control rates that can be obtained using low-dose involved field radiotherapy (IFRT).

Low-dose IFRT has now become a standard of care in the United States, although approaches still vary in Europe, he reported May 9 at the European Society for Therapeutic Radiation Oncology Anniversary Conference.

Indeed, the latest guidelines set by the National Comprehensive Cancer Network on non-Hodgkin’s lymphomas – which includes gastric MALT (mucosa-associated lymphoid tissue) lymphoma of the stomach – recommend the use of radiotherapy as a first-line option when patients have early (stage I/II) H. pylori–negative disease.

"We started using this [low-dose irradiation] treatment approach in the early 90s. Until then, the standard treatment for this lymphoma in the stomach was total gastrectomy, and sometimes it was followed by radiation therapy," said Dr. Yahalom, a professor of radiation oncology at Cornell University in New York. He added that chemotherapy and rituximab (Rituxan) were not generally very effective.

"Obviously the treatment of choice is to give antibiotics if H. pylori is present," Dr. Yahalom added, noting that substantial regression of MALT lymphoma can occur via treatment with antibiotics that target the gastric bacterium in positive cases. However, when H. pylori is not present, or if there is a lack of response to or residual lymphoma after complete response to antibiotic therapy, then radiotherapy is the recommended next step.

Dr. Yahalom presented data representing 16 years of experience in treating 103 patients (60 women and 43 men) with gastric MALT lymphoma in 1992-2009. The majority of patients (76%) had stage I disease, with 19% having stage II, and fewer than 5% having stage IV.

The median age of the patients was 62 years (range, 25-91 years). Symptoms were relatively mild at presentation, Dr. Yahalom observed: In all, 52% had epigastric pain, 36% had nausea, 29% had gastric bleeding, 18% had anorexia, 15% had anemia, and 10% had unknown or no obvious symptoms.

Almost two-thirds of patients were H. pylori negative. This included four patients who had relapsed after a complete response to antibiotic therapy. A further 20% of patients had persistent lymphoma after H. pylori eradication therapy. Another 15% had H. pylori and lymphoma remaining after antibiotic treatment, but had progressive symptoms or disease that could not wait for another antibiotics trial.

Prior to being treated with IFRT, six patients had undergone surgery, and seven had received medications that failed to control their disease.

Approximately 90% of patients were given IFRT at a median dose of 30 Gy in 1.5 Gy fractions for 4 weeks. The lowest and highest total radiation doses administered were 22.5 Gy and 43.5 Gy.

Patients received regular follow up via endoscopic biopsies, and after a median of 5.5 years, the disease control rate was 98%. One-fifth of patients had been followed for 10 years, and the 10-year freedom from local failure was 93%; the 10-year overall survival rate was 74%.

There were no significant acute or late adverse events, Dr. Yahalom noted, and just eight patients relapsed (six with gastric MALT lymphoma and two with diffuse large B-cell lymphoma). Subsequent other cancers included lymphoma in extragastric sites (eight patients), adenocarcinoma of the stomach (two), and second tumors close to the radiotherapy field (one in the colon and two in the pancreas). "Other deaths appeared unrelated to disease or treatment," he said.

Based on this experience, Dr. Yahalom concluded that "low-dose irradiation of the stomach provides excellent long-term disease control [and] is safe and simple.

"Radiation therapy, in our opinion, is the treatment of choice for patients with MALT lymphoma that have exhausted their antibiotic options or are unlikely to respond to it."

Dr. Yahalom said he had no financial conflicts of interest.

LONDON – Proton beam therapy for non–small cell lung cancer is associated with fewer radiation-induced side effects than are conventional radiotherapy methods when combined with chemotherapy, according to preliminary data from two retrospective studies conducted at the University of Texas M.D. Anderson Cancer Center in Houston.

Significantly less esophagitis, pneumonitis, and bone marrow toxicity were observed with proton beam therapy (PBT) than with intensity-modulated radiotherapy (IMRT), Dr. Ritsuko Komaki reported May 10, at the European Society for Therapeutic Radiation Oncology (ESTRO) Anniversary Conference.

Photo credit: M.D. Anderson Cancer Center

Proton beam therapy also significantly reduced the incidence of esophagitis when compared with IMRT and three-dimensional conformal radiotherapy (3D-CRT). A mean esophageal dose of 40 Gy or higher was identified as the cut-off point for high-grade esophagitis occurring with any method.

"Radiation dose escalation improves local control but increases toxicity, especially when combined with concurrent chemotherapy for non–small cell lung cancer [NSCLC] or even small cell lung cancer," said Dr. Komaki, a professor of radiation oncology at M.D. Anderson, which opened its 94,000-square-foot Proton Therapy Center in 2006. As such, "radiation chemotherapy is a double-edged sword," she observed. "It will kill cancer cells, but it also kills normal tissues, and more targeted treatment is needed."

"One of the most important benefits of PBT is that there is no exit dose," Dr. Komaki added in an interview with Elsevier Global Medical News. "The protons stop after penetrating the tumor, and there is no dose of radiation beyond it."

This has the potential to spare surrounding cells and organs from damage, she observed. Normal tissues that might be affected by radiation therapy for NSCLC include the lungs, esophagus, heart, and bone marrow, which cannot always be avoided by the use of 3D-CRT or even IMRT.

An expensive new technology that delivers highly targeted radiation with electrically charged particles, proton beam therapy is promising but unproven, according to a 2009 review commissioned by the Agency for Healthcare Research and Quality (AHRQ). The authors found few comparative studies to establish effectiveness or safety for the technology, which is housed in a small but growing number of proton beam centers that can cost $100 million to $225 million to build (Ann. Intern. Med. 2009;151:556-65).

Dr. Komaki and her associates are recruiting patients into the first, prospective randomized trial to directly compare proton beam therapy with IMRT in unresectable stage II /III NSCLC. The phase II trial is supported by a grant from the National Cancer Institute, and involves treatment with 74 Gy proton beam therapy or IMRT with concurrent carboplatin and paclitaxel. To date, 107 of the planned 168 patients have been enrolled in the study at the Texas institution and at the Massachusetts General Hospital in Boston, the other participating center, she said.

A recent report from the M.D. Anderson showed that higher doses of proton radiation could be delivered to lung tumors with a lower risk of esophagitis and pneumonitis than either IMRT or 3D-CRT (Cancer 2011;doi.org/10.1002/cncr.25848).

The new data presented by Dr. Komaki showed significantly reduced rates of grade 2 or higher esophagitis (P less than .0001), pneumonitis (P less than .002), hematologic toxicities (P less than .0001 for neutrophil toxicity and P less than .001 for hemoglobin and white blood cell toxicities), and fatigue (P less than.0001) in 60 patients treated with proton beam therapy compared with 75 patients treated with IMRT (Radiother. Oncol. 2011;99:S89-90, abstract 233).

Other research from the M.D. Anderson team focused on esophagitis, and examined dosimetric and clinical factors that could lead to this side effect following proton beam therapy, IMRT, or 3D-CRT for definitive NSCLC treatment (Radiother. Oncol. 2011;99[Suppl.1]:S210, abstract 518).

Dr. Daniel Gomez, a radiation oncologist at M.D. Anderson, presented data on 678 patients treated at the institution between 1999 and 2008. Dr. Gomez explained that the type of radiation therapy received had altered over the years, with 463 patients treated with 3D-CRT between 1999 and 2005, 122 with IMRT between 2005 and 2007, and 94 patients treated with proton beam therapy between 2006 and 2008.

"Esophagitis is a common toxicity in the treatment of NSCLC with definitive radiation," Dr. Gomez observed. Although studies have looked at what factors might predict this life-limiting side effect, conflicting results have been obtained.

Data show, for example, that the presence of acute toxicity is a predictor of late toxicity (Int. J. Radiat. Oncol. Biol. Phys. 2005,61:335-47), but a variety of dosimetric parameters have been noted and there does not appear to be a single threshold at which a toxic effect is or is not likely to be observed (Int. J. Radiat. Oncol. Biol. Phys. 2010;76:S86-93).

Data presented by Dr. Gomez, however, suggest that a mean delivered esophageal dose of above 40 Gy may be predictive of high-grade inflammation regardless of whether proton beams, IMRT or 3D-CRT is used. This research might eventually help develop dosing guides for clinicians to use in routine practice, he suggested.

"Patients receiving IMRT had a higher rate of esophagitis in all grades, including grade 3," Dr. Gomez said. In contrast, "patients receiving proton therapy had lower rates of esophagitis at all grades." The incidence of grade 3 or higher esophagitis was 14% (n = 65) for 3D-CRT, 27% (n = 33) for IMRT, and 6% (n = 6) for proton beam therapy.

Dr. Gomez also reported that grade 3 or higher esophagitis was more likely in patients who received concurrent chemotherapy than in those who did not (18.4% vs. 7.4%, P less than .001). The mean esophageal dose of radiation delivered to patients given concurrent chemotherapy also was, significantly higher (32.2 Gy vs. 15.8 Gy, P less than .001), however.

The M.D. Anderson investigators said they have just finished (May 12) recruiting patients into a phase III trial (Radiation Therapy Oncology Group [RTOG] 0617) that will compare conventional (60 Gy in 6 weeks) vs. high dose (74 Gy in 7.5 weeks) radiation therapy in combination with paclitaxel and carboplatin, with or without the addition of cetuximab (Erbitux) in 500 patients with NSCLC.

Although the trial is not directly comparing the type of radiation treatment used, it should still be possible to retrospectively analyze the results to determine the individual effects of the radiation modalities used at each participating center, Dr. Komaki noted.

"When we started this trial, it was not acquiring patients because some of the radiation and medical oncologists said that it was obvious that patients given 60 Gy would do worse compared to 74 Gy," she added in the interview. "When we included cetuximab based on the results of the RTOG 0324 trial, however, recruitment started to rocket." The RTOG 0324 trial showed the feasibility of combining cetuximab with chemoradiation in NSCLC (J. Clin. Oncol. 2011 May 9 [Epub ahead of print, doi: 10.1200/JCO.2010.31.7875]).

Discussing the downsides of proton beam therapy vs. IMRT, Dr. Komaki conceded that the newer method involved a lot more sophisticated planning and was more expensive. There is also concern that the sharp drop-off of radiation received with proton beam therapy might mean that important areas of the tumor are missed – although this may explain the lower rate of side effects seen with PBT to date. "There is no give," Dr. Komaki said.

As relatively few proton beam facilities are in operation, large cooperative trials are difficult to perform. The prospective phase II trial comparing proton beam therapy and IMRT now being conducted at M.D. Anderson and the Massachusetts General Hospital will be the proof that such trials are possible, and provide valuable information on the comparative safety and efficacy of the two procedures.

Dr. Komaki and Dr. Gomez said they had no financial conflicts of interest.

LONDON – Proton beam therapy for non–small cell lung cancer is associated with fewer radiation-induced side effects than are conventional radiotherapy methods when combined with chemotherapy, according to preliminary data from two retrospective studies conducted at the University of Texas M.D. Anderson Cancer Center in Houston.

Significantly less esophagitis, pneumonitis, and bone marrow toxicity were observed with proton beam therapy (PBT) than with intensity-modulated radiotherapy (IMRT), Dr. Ritsuko Komaki reported May 10, at the European Society for Therapeutic Radiation Oncology (ESTRO) Anniversary Conference.

Photo credit: M.D. Anderson Cancer Center

Proton beam therapy also significantly reduced the incidence of esophagitis when compared with IMRT and three-dimensional conformal radiotherapy (3D-CRT). A mean esophageal dose of 40 Gy or higher was identified as the cut-off point for high-grade esophagitis occurring with any method.

"Radiation dose escalation improves local control but increases toxicity, especially when combined with concurrent chemotherapy for non–small cell lung cancer [NSCLC] or even small cell lung cancer," said Dr. Komaki, a professor of radiation oncology at M.D. Anderson, which opened its 94,000-square-foot Proton Therapy Center in 2006. As such, "radiation chemotherapy is a double-edged sword," she observed. "It will kill cancer cells, but it also kills normal tissues, and more targeted treatment is needed."

"One of the most important benefits of PBT is that there is no exit dose," Dr. Komaki added in an interview with Elsevier Global Medical News. "The protons stop after penetrating the tumor, and there is no dose of radiation beyond it."

This has the potential to spare surrounding cells and organs from damage, she observed. Normal tissues that might be affected by radiation therapy for NSCLC include the lungs, esophagus, heart, and bone marrow, which cannot always be avoided by the use of 3D-CRT or even IMRT.

An expensive new technology that delivers highly targeted radiation with electrically charged particles, proton beam therapy is promising but unproven, according to a 2009 review commissioned by the Agency for Healthcare Research and Quality (AHRQ). The authors found few comparative studies to establish effectiveness or safety for the technology, which is housed in a small but growing number of proton beam centers that can cost $100 million to $225 million to build (Ann. Intern. Med. 2009;151:556-65).

Dr. Komaki and her associates are recruiting patients into the first, prospective randomized trial to directly compare proton beam therapy with IMRT in unresectable stage II /III NSCLC. The phase II trial is supported by a grant from the National Cancer Institute, and involves treatment with 74 Gy proton beam therapy or IMRT with concurrent carboplatin and paclitaxel. To date, 107 of the planned 168 patients have been enrolled in the study at the Texas institution and at the Massachusetts General Hospital in Boston, the other participating center, she said.

A recent report from the M.D. Anderson showed that higher doses of proton radiation could be delivered to lung tumors with a lower risk of esophagitis and pneumonitis than either IMRT or 3D-CRT (Cancer 2011;doi.org/10.1002/cncr.25848).

The new data presented by Dr. Komaki showed significantly reduced rates of grade 2 or higher esophagitis (P less than .0001), pneumonitis (P less than .002), hematologic toxicities (P less than .0001 for neutrophil toxicity and P less than .001 for hemoglobin and white blood cell toxicities), and fatigue (P less than.0001) in 60 patients treated with proton beam therapy compared with 75 patients treated with IMRT (Radiother. Oncol. 2011;99:S89-90, abstract 233).

Other research from the M.D. Anderson team focused on esophagitis, and examined dosimetric and clinical factors that could lead to this side effect following proton beam therapy, IMRT, or 3D-CRT for definitive NSCLC treatment (Radiother. Oncol. 2011;99[Suppl.1]:S210, abstract 518).

Dr. Daniel Gomez, a radiation oncologist at M.D. Anderson, presented data on 678 patients treated at the institution between 1999 and 2008. Dr. Gomez explained that the type of radiation therapy received had altered over the years, with 463 patients treated with 3D-CRT between 1999 and 2005, 122 with IMRT between 2005 and 2007, and 94 patients treated with proton beam therapy between 2006 and 2008.

"Esophagitis is a common toxicity in the treatment of NSCLC with definitive radiation," Dr. Gomez observed. Although studies have looked at what factors might predict this life-limiting side effect, conflicting results have been obtained.

Data show, for example, that the presence of acute toxicity is a predictor of late toxicity (Int. J. Radiat. Oncol. Biol. Phys. 2005,61:335-47), but a variety of dosimetric parameters have been noted and there does not appear to be a single threshold at which a toxic effect is or is not likely to be observed (Int. J. Radiat. Oncol. Biol. Phys. 2010;76:S86-93).

Data presented by Dr. Gomez, however, suggest that a mean delivered esophageal dose of above 40 Gy may be predictive of high-grade inflammation regardless of whether proton beams, IMRT or 3D-CRT is used. This research might eventually help develop dosing guides for clinicians to use in routine practice, he suggested.

"Patients receiving IMRT had a higher rate of esophagitis in all grades, including grade 3," Dr. Gomez said. In contrast, "patients receiving proton therapy had lower rates of esophagitis at all grades." The incidence of grade 3 or higher esophagitis was 14% (n = 65) for 3D-CRT, 27% (n = 33) for IMRT, and 6% (n = 6) for proton beam therapy.

Dr. Gomez also reported that grade 3 or higher esophagitis was more likely in patients who received concurrent chemotherapy than in those who did not (18.4% vs. 7.4%, P less than .001). The mean esophageal dose of radiation delivered to patients given concurrent chemotherapy also was, significantly higher (32.2 Gy vs. 15.8 Gy, P less than .001), however.

The M.D. Anderson investigators said they have just finished (May 12) recruiting patients into a phase III trial (Radiation Therapy Oncology Group [RTOG] 0617) that will compare conventional (60 Gy in 6 weeks) vs. high dose (74 Gy in 7.5 weeks) radiation therapy in combination with paclitaxel and carboplatin, with or without the addition of cetuximab (Erbitux) in 500 patients with NSCLC.

Although the trial is not directly comparing the type of radiation treatment used, it should still be possible to retrospectively analyze the results to determine the individual effects of the radiation modalities used at each participating center, Dr. Komaki noted.

"When we started this trial, it was not acquiring patients because some of the radiation and medical oncologists said that it was obvious that patients given 60 Gy would do worse compared to 74 Gy," she added in the interview. "When we included cetuximab based on the results of the RTOG 0324 trial, however, recruitment started to rocket." The RTOG 0324 trial showed the feasibility of combining cetuximab with chemoradiation in NSCLC (J. Clin. Oncol. 2011 May 9 [Epub ahead of print, doi: 10.1200/JCO.2010.31.7875]).

Discussing the downsides of proton beam therapy vs. IMRT, Dr. Komaki conceded that the newer method involved a lot more sophisticated planning and was more expensive. There is also concern that the sharp drop-off of radiation received with proton beam therapy might mean that important areas of the tumor are missed – although this may explain the lower rate of side effects seen with PBT to date. "There is no give," Dr. Komaki said.

As relatively few proton beam facilities are in operation, large cooperative trials are difficult to perform. The prospective phase II trial comparing proton beam therapy and IMRT now being conducted at M.D. Anderson and the Massachusetts General Hospital will be the proof that such trials are possible, and provide valuable information on the comparative safety and efficacy of the two procedures.

Dr. Komaki and Dr. Gomez said they had no financial conflicts of interest.

LONDON – Proton beam therapy for non–small cell lung cancer is associated with fewer radiation-induced side effects than are conventional radiotherapy methods when combined with chemotherapy, according to preliminary data from two retrospective studies conducted at the University of Texas M.D. Anderson Cancer Center in Houston.

Significantly less esophagitis, pneumonitis, and bone marrow toxicity were observed with proton beam therapy (PBT) than with intensity-modulated radiotherapy (IMRT), Dr. Ritsuko Komaki reported May 10, at the European Society for Therapeutic Radiation Oncology (ESTRO) Anniversary Conference.

Photo credit: M.D. Anderson Cancer Center

Proton beam therapy also significantly reduced the incidence of esophagitis when compared with IMRT and three-dimensional conformal radiotherapy (3D-CRT). A mean esophageal dose of 40 Gy or higher was identified as the cut-off point for high-grade esophagitis occurring with any method.

"Radiation dose escalation improves local control but increases toxicity, especially when combined with concurrent chemotherapy for non–small cell lung cancer [NSCLC] or even small cell lung cancer," said Dr. Komaki, a professor of radiation oncology at M.D. Anderson, which opened its 94,000-square-foot Proton Therapy Center in 2006. As such, "radiation chemotherapy is a double-edged sword," she observed. "It will kill cancer cells, but it also kills normal tissues, and more targeted treatment is needed."

"One of the most important benefits of PBT is that there is no exit dose," Dr. Komaki added in an interview with Elsevier Global Medical News. "The protons stop after penetrating the tumor, and there is no dose of radiation beyond it."

This has the potential to spare surrounding cells and organs from damage, she observed. Normal tissues that might be affected by radiation therapy for NSCLC include the lungs, esophagus, heart, and bone marrow, which cannot always be avoided by the use of 3D-CRT or even IMRT.

An expensive new technology that delivers highly targeted radiation with electrically charged particles, proton beam therapy is promising but unproven, according to a 2009 review commissioned by the Agency for Healthcare Research and Quality (AHRQ). The authors found few comparative studies to establish effectiveness or safety for the technology, which is housed in a small but growing number of proton beam centers that can cost $100 million to $225 million to build (Ann. Intern. Med. 2009;151:556-65).

Dr. Komaki and her associates are recruiting patients into the first, prospective randomized trial to directly compare proton beam therapy with IMRT in unresectable stage II /III NSCLC. The phase II trial is supported by a grant from the National Cancer Institute, and involves treatment with 74 Gy proton beam therapy or IMRT with concurrent carboplatin and paclitaxel. To date, 107 of the planned 168 patients have been enrolled in the study at the Texas institution and at the Massachusetts General Hospital in Boston, the other participating center, she said.

A recent report from the M.D. Anderson showed that higher doses of proton radiation could be delivered to lung tumors with a lower risk of esophagitis and pneumonitis than either IMRT or 3D-CRT (Cancer 2011;doi.org/10.1002/cncr.25848).

The new data presented by Dr. Komaki showed significantly reduced rates of grade 2 or higher esophagitis (P less than .0001), pneumonitis (P less than .002), hematologic toxicities (P less than .0001 for neutrophil toxicity and P less than .001 for hemoglobin and white blood cell toxicities), and fatigue (P less than.0001) in 60 patients treated with proton beam therapy compared with 75 patients treated with IMRT (Radiother. Oncol. 2011;99:S89-90, abstract 233).

Other research from the M.D. Anderson team focused on esophagitis, and examined dosimetric and clinical factors that could lead to this side effect following proton beam therapy, IMRT, or 3D-CRT for definitive NSCLC treatment (Radiother. Oncol. 2011;99[Suppl.1]:S210, abstract 518).

Dr. Daniel Gomez, a radiation oncologist at M.D. Anderson, presented data on 678 patients treated at the institution between 1999 and 2008. Dr. Gomez explained that the type of radiation therapy received had altered over the years, with 463 patients treated with 3D-CRT between 1999 and 2005, 122 with IMRT between 2005 and 2007, and 94 patients treated with proton beam therapy between 2006 and 2008.

"Esophagitis is a common toxicity in the treatment of NSCLC with definitive radiation," Dr. Gomez observed. Although studies have looked at what factors might predict this life-limiting side effect, conflicting results have been obtained.

Data show, for example, that the presence of acute toxicity is a predictor of late toxicity (Int. J. Radiat. Oncol. Biol. Phys. 2005,61:335-47), but a variety of dosimetric parameters have been noted and there does not appear to be a single threshold at which a toxic effect is or is not likely to be observed (Int. J. Radiat. Oncol. Biol. Phys. 2010;76:S86-93).

Data presented by Dr. Gomez, however, suggest that a mean delivered esophageal dose of above 40 Gy may be predictive of high-grade inflammation regardless of whether proton beams, IMRT or 3D-CRT is used. This research might eventually help develop dosing guides for clinicians to use in routine practice, he suggested.

"Patients receiving IMRT had a higher rate of esophagitis in all grades, including grade 3," Dr. Gomez said. In contrast, "patients receiving proton therapy had lower rates of esophagitis at all grades." The incidence of grade 3 or higher esophagitis was 14% (n = 65) for 3D-CRT, 27% (n = 33) for IMRT, and 6% (n = 6) for proton beam therapy.

Dr. Gomez also reported that grade 3 or higher esophagitis was more likely in patients who received concurrent chemotherapy than in those who did not (18.4% vs. 7.4%, P less than .001). The mean esophageal dose of radiation delivered to patients given concurrent chemotherapy also was, significantly higher (32.2 Gy vs. 15.8 Gy, P less than .001), however.

The M.D. Anderson investigators said they have just finished (May 12) recruiting patients into a phase III trial (Radiation Therapy Oncology Group [RTOG] 0617) that will compare conventional (60 Gy in 6 weeks) vs. high dose (74 Gy in 7.5 weeks) radiation therapy in combination with paclitaxel and carboplatin, with or without the addition of cetuximab (Erbitux) in 500 patients with NSCLC.

Although the trial is not directly comparing the type of radiation treatment used, it should still be possible to retrospectively analyze the results to determine the individual effects of the radiation modalities used at each participating center, Dr. Komaki noted.

"When we started this trial, it was not acquiring patients because some of the radiation and medical oncologists said that it was obvious that patients given 60 Gy would do worse compared to 74 Gy," she added in the interview. "When we included cetuximab based on the results of the RTOG 0324 trial, however, recruitment started to rocket." The RTOG 0324 trial showed the feasibility of combining cetuximab with chemoradiation in NSCLC (J. Clin. Oncol. 2011 May 9 [Epub ahead of print, doi: 10.1200/JCO.2010.31.7875]).

Discussing the downsides of proton beam therapy vs. IMRT, Dr. Komaki conceded that the newer method involved a lot more sophisticated planning and was more expensive. There is also concern that the sharp drop-off of radiation received with proton beam therapy might mean that important areas of the tumor are missed – although this may explain the lower rate of side effects seen with PBT to date. "There is no give," Dr. Komaki said.

As relatively few proton beam facilities are in operation, large cooperative trials are difficult to perform. The prospective phase II trial comparing proton beam therapy and IMRT now being conducted at M.D. Anderson and the Massachusetts General Hospital will be the proof that such trials are possible, and provide valuable information on the comparative safety and efficacy of the two procedures.

Dr. Komaki and Dr. Gomez said they had no financial conflicts of interest.