Patient & Survivor Care

NATIONAL HARBOR, MD. – Extended-release gabapentin at daily doses of either 1,200 mg or 1,800 mg significantly reduced the number and severity of hot flashes and significantly improved sleep problems, compared with a placebo, in postmenopausal women.

Currently, hormone therapy is the only approved treatment for hot flashes in North America and Europe, according to Dr. Mira Baron of Rapid Medical Research Inc., Cleveland, and colleagues.

In previous studies, gabapentin has shown effectiveness in reducing the frequency and severity of hot flashes, but its short half-life may limit its usefulness, the researchers said. However, an extended-release, once-daily dose of gabapentin was approved by the U.S. Food and Drug Administration in February 2011 to treat postherpetic neuralgia, she said at the annual meeting of the North American Menopause Society.

In Breeze 2, a phase III, double-blind, placebo-controlled trial conducted at 45 sites in the United States, Dr. Baron and colleagues compared the effectiveness of 1,200 mg of extended-release gabapentin once daily vs. 1,800 mg twice daily (600 mg in the morning and 1,200 mg at night) on the frequency and severity of hot flashes.

A total of 559 women completed 12 weeks of treatment and were included in the intent-to-treat population; 190 were randomized to once-daily treatment, 186 were randomized to twice-daily treatment, and 183 were randomized to a placebo. Participants used an electronic diary to record the frequency and severity of their hot flashes during the study.

The average age of the patients was 53 years, and the mean age at menopause was 44 years. The eligible participants reported at least seven moderate to severe hot flashes per day during a 1-week baseline period before they started the study.

Overall, the median daily number of hot flashes dropped significantly after 12 weeks of treatment in both treatment groups, compared with the placebo group. The number of daily hot flashes dropped to three in the placebo group and to two in the two treatment groups.

In addition, the severity of the hot flashes decreased significantly from baseline in both treatment groups, compared with the placebo group. The mean change in vasomotor severity score, compared with baseline, was –0.9 in the once-daily group, –0.8 in the twice-daily group, and –0.6 in the placebo group. The reduction in the severity of vasomotor symptoms was significant for both treatment doses, compared with the placebo. "However, the 1,800-mg dosage yielded more significant changes than the 1,200-mg dosage," the researchers noted.

In a second study, Dr. Risa Kagan of the Alta Bates Summit Medical Center in Berkeley, Calif., and colleagues studied the effectiveness of extended-release gabapentin on improving the sleep problems commonly reported by postmenopausal women.

The researchers compared the effects of extended-release gabapentin vs. a placebo on sleep problems in postmenopausal women using data from the Breeze 1 study, which was a phase III, double-blind, placebo-controlled trial conducted at 48 sites in the United States. A total of 531 women made up the intent-to-treat population, and they were randomized to gabapentin 1,200 mg once daily, to 1,800 mg twice daily (600 mg in the morning and 1,200 mg at night), or to a placebo.

Overall, global scores on the PSQI (Pittsburgh Sleep Quality Index) improved significantly with both gabapentin doses, compared with the placebo, at three separate time points.

After 4 weeks, the mean difference in the global PSQI scores was –1.74 in the once-daily group and –1.68 in the twice-daily group. After 12 weeks, the mean differences in the global PSQI scores for the two treatment groups, compared with placebo, were –1.16 and –0.80, respectively. After 24 weeks, the mean differences in the global PSQI scores for the two treatment groups, compared with placebo, were –0.77 and –0.93, respectively.

"The largest differences between the active arms and the placebo arm were observed at week 4," the researchers said. "The decrease in the magnitude of improvement over time likely resulted from the fact that the PSQI instrument requests reporting for the previous 4 weeks." However, the global scores did improve throughout the study, they noted.

No significant difference in daytime dysfunction scores was observed between either of the treatment groups and the placebo group.

Although the drug is not currently approved for this indication, the findings suggest that extended-release gabapentin might have potential as a treatment option for hot flashes and sleep disturbances in postmenopausal women who are reluctant to use hormonal therapies, the researchers said.

The studies were supported by Depomed. Dr. Baron had no personal financial conflicts to disclose. One of the study coauthors on her study is an employee of Depomed. Dr. Kagan disclosed serving as a consultant or advisory board member for multiple companies, including Amgen, Bionovo, Depomed, Merck, Pfizer, and Shionogi. She disclosed receiving research support from Bionovo, BioSante Pharmaceuticals, Boehringer-Ingelheim, Depomed, and Pfizer, and serving on the speakers bureau for Amgen, Novogyne, and Novo Nordisk.

NATIONAL HARBOR, MD. – Extended-release gabapentin at daily doses of either 1,200 mg or 1,800 mg significantly reduced the number and severity of hot flashes and significantly improved sleep problems, compared with a placebo, in postmenopausal women.

Currently, hormone therapy is the only approved treatment for hot flashes in North America and Europe, according to Dr. Mira Baron of Rapid Medical Research Inc., Cleveland, and colleagues.

In previous studies, gabapentin has shown effectiveness in reducing the frequency and severity of hot flashes, but its short half-life may limit its usefulness, the researchers said. However, an extended-release, once-daily dose of gabapentin was approved by the U.S. Food and Drug Administration in February 2011 to treat postherpetic neuralgia, she said at the annual meeting of the North American Menopause Society.

In Breeze 2, a phase III, double-blind, placebo-controlled trial conducted at 45 sites in the United States, Dr. Baron and colleagues compared the effectiveness of 1,200 mg of extended-release gabapentin once daily vs. 1,800 mg twice daily (600 mg in the morning and 1,200 mg at night) on the frequency and severity of hot flashes.

A total of 559 women completed 12 weeks of treatment and were included in the intent-to-treat population; 190 were randomized to once-daily treatment, 186 were randomized to twice-daily treatment, and 183 were randomized to a placebo. Participants used an electronic diary to record the frequency and severity of their hot flashes during the study.

The average age of the patients was 53 years, and the mean age at menopause was 44 years. The eligible participants reported at least seven moderate to severe hot flashes per day during a 1-week baseline period before they started the study.

Overall, the median daily number of hot flashes dropped significantly after 12 weeks of treatment in both treatment groups, compared with the placebo group. The number of daily hot flashes dropped to three in the placebo group and to two in the two treatment groups.

In addition, the severity of the hot flashes decreased significantly from baseline in both treatment groups, compared with the placebo group. The mean change in vasomotor severity score, compared with baseline, was –0.9 in the once-daily group, –0.8 in the twice-daily group, and –0.6 in the placebo group. The reduction in the severity of vasomotor symptoms was significant for both treatment doses, compared with the placebo. "However, the 1,800-mg dosage yielded more significant changes than the 1,200-mg dosage," the researchers noted.

In a second study, Dr. Risa Kagan of the Alta Bates Summit Medical Center in Berkeley, Calif., and colleagues studied the effectiveness of extended-release gabapentin on improving the sleep problems commonly reported by postmenopausal women.

The researchers compared the effects of extended-release gabapentin vs. a placebo on sleep problems in postmenopausal women using data from the Breeze 1 study, which was a phase III, double-blind, placebo-controlled trial conducted at 48 sites in the United States. A total of 531 women made up the intent-to-treat population, and they were randomized to gabapentin 1,200 mg once daily, to 1,800 mg twice daily (600 mg in the morning and 1,200 mg at night), or to a placebo.

Overall, global scores on the PSQI (Pittsburgh Sleep Quality Index) improved significantly with both gabapentin doses, compared with the placebo, at three separate time points.

After 4 weeks, the mean difference in the global PSQI scores was –1.74 in the once-daily group and –1.68 in the twice-daily group. After 12 weeks, the mean differences in the global PSQI scores for the two treatment groups, compared with placebo, were –1.16 and –0.80, respectively. After 24 weeks, the mean differences in the global PSQI scores for the two treatment groups, compared with placebo, were –0.77 and –0.93, respectively.

"The largest differences between the active arms and the placebo arm were observed at week 4," the researchers said. "The decrease in the magnitude of improvement over time likely resulted from the fact that the PSQI instrument requests reporting for the previous 4 weeks." However, the global scores did improve throughout the study, they noted.

No significant difference in daytime dysfunction scores was observed between either of the treatment groups and the placebo group.

Although the drug is not currently approved for this indication, the findings suggest that extended-release gabapentin might have potential as a treatment option for hot flashes and sleep disturbances in postmenopausal women who are reluctant to use hormonal therapies, the researchers said.

The studies were supported by Depomed. Dr. Baron had no personal financial conflicts to disclose. One of the study coauthors on her study is an employee of Depomed. Dr. Kagan disclosed serving as a consultant or advisory board member for multiple companies, including Amgen, Bionovo, Depomed, Merck, Pfizer, and Shionogi. She disclosed receiving research support from Bionovo, BioSante Pharmaceuticals, Boehringer-Ingelheim, Depomed, and Pfizer, and serving on the speakers bureau for Amgen, Novogyne, and Novo Nordisk.

NATIONAL HARBOR, MD. – Extended-release gabapentin at daily doses of either 1,200 mg or 1,800 mg significantly reduced the number and severity of hot flashes and significantly improved sleep problems, compared with a placebo, in postmenopausal women.

Currently, hormone therapy is the only approved treatment for hot flashes in North America and Europe, according to Dr. Mira Baron of Rapid Medical Research Inc., Cleveland, and colleagues.

In previous studies, gabapentin has shown effectiveness in reducing the frequency and severity of hot flashes, but its short half-life may limit its usefulness, the researchers said. However, an extended-release, once-daily dose of gabapentin was approved by the U.S. Food and Drug Administration in February 2011 to treat postherpetic neuralgia, she said at the annual meeting of the North American Menopause Society.

In Breeze 2, a phase III, double-blind, placebo-controlled trial conducted at 45 sites in the United States, Dr. Baron and colleagues compared the effectiveness of 1,200 mg of extended-release gabapentin once daily vs. 1,800 mg twice daily (600 mg in the morning and 1,200 mg at night) on the frequency and severity of hot flashes.

A total of 559 women completed 12 weeks of treatment and were included in the intent-to-treat population; 190 were randomized to once-daily treatment, 186 were randomized to twice-daily treatment, and 183 were randomized to a placebo. Participants used an electronic diary to record the frequency and severity of their hot flashes during the study.

The average age of the patients was 53 years, and the mean age at menopause was 44 years. The eligible participants reported at least seven moderate to severe hot flashes per day during a 1-week baseline period before they started the study.

Overall, the median daily number of hot flashes dropped significantly after 12 weeks of treatment in both treatment groups, compared with the placebo group. The number of daily hot flashes dropped to three in the placebo group and to two in the two treatment groups.

In addition, the severity of the hot flashes decreased significantly from baseline in both treatment groups, compared with the placebo group. The mean change in vasomotor severity score, compared with baseline, was –0.9 in the once-daily group, –0.8 in the twice-daily group, and –0.6 in the placebo group. The reduction in the severity of vasomotor symptoms was significant for both treatment doses, compared with the placebo. "However, the 1,800-mg dosage yielded more significant changes than the 1,200-mg dosage," the researchers noted.

In a second study, Dr. Risa Kagan of the Alta Bates Summit Medical Center in Berkeley, Calif., and colleagues studied the effectiveness of extended-release gabapentin on improving the sleep problems commonly reported by postmenopausal women.

The researchers compared the effects of extended-release gabapentin vs. a placebo on sleep problems in postmenopausal women using data from the Breeze 1 study, which was a phase III, double-blind, placebo-controlled trial conducted at 48 sites in the United States. A total of 531 women made up the intent-to-treat population, and they were randomized to gabapentin 1,200 mg once daily, to 1,800 mg twice daily (600 mg in the morning and 1,200 mg at night), or to a placebo.

Overall, global scores on the PSQI (Pittsburgh Sleep Quality Index) improved significantly with both gabapentin doses, compared with the placebo, at three separate time points.

After 4 weeks, the mean difference in the global PSQI scores was –1.74 in the once-daily group and –1.68 in the twice-daily group. After 12 weeks, the mean differences in the global PSQI scores for the two treatment groups, compared with placebo, were –1.16 and –0.80, respectively. After 24 weeks, the mean differences in the global PSQI scores for the two treatment groups, compared with placebo, were –0.77 and –0.93, respectively.

"The largest differences between the active arms and the placebo arm were observed at week 4," the researchers said. "The decrease in the magnitude of improvement over time likely resulted from the fact that the PSQI instrument requests reporting for the previous 4 weeks." However, the global scores did improve throughout the study, they noted.

No significant difference in daytime dysfunction scores was observed between either of the treatment groups and the placebo group.

Although the drug is not currently approved for this indication, the findings suggest that extended-release gabapentin might have potential as a treatment option for hot flashes and sleep disturbances in postmenopausal women who are reluctant to use hormonal therapies, the researchers said.

The studies were supported by Depomed. Dr. Baron had no personal financial conflicts to disclose. One of the study coauthors on her study is an employee of Depomed. Dr. Kagan disclosed serving as a consultant or advisory board member for multiple companies, including Amgen, Bionovo, Depomed, Merck, Pfizer, and Shionogi. She disclosed receiving research support from Bionovo, BioSante Pharmaceuticals, Boehringer-Ingelheim, Depomed, and Pfizer, and serving on the speakers bureau for Amgen, Novogyne, and Novo Nordisk.

STOCKHOLM – Denosumab prolongs bone metastasis-free survival across a variety of nonmetastatic, castrate-resistant prostate cancer subgroups, according to subanalyses of a phase III study.

Denosumab (Xgeva) improved bone metastasis-free survival compared with placebo in men with dual prostate-specific antigen risk factors (hazard ratio, 0.83; P = .07), a single PSA risk factor (HR, 0.87; P = .20), a Gleason score of 2-7 (HR, 0.85, P = .12), and Gleason score of 8-10 (HR, 0.81; P = .10).

The advantage with denosumab was observed regardless of patient age, geographic region, or race, Dr. Stephane Oudard said at the European Multidisciplinary Cancer Congress.

Overall, the primary end point of bone metastasis-free survival was increased from 25.2 months with placebo to 29.5 months with denosumab. This corresponds to a relative risk reduction of 15% (hazard ratio, 0.85; P = .028).

Dr. Oudard pointed out that nearly all men with prostate cancer develop bone metastases, and that this is "the first randomized study to demonstrate that targeting bone microenvironment prevents bone metastasis in men with prostate cancer."

Denosumab is a monoclonal antibody that inhibits RANK ligand, a key mediator of bone osteoclast activity. The drug was approved in 2010 for the treatment of postmenopausal osteoporosis under the trade name Prolia, and later that year for the prevention of skeletal-related events in patients with bone metastases from solid tumors.

In September 2011, two new indications were added for denosumab: to increase bone mass in patients at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer, or adjuvant aromatase inhibitor therapy for breast cancer.

The phase III denosumab 147 study evenly randomized 1,432 men with nonmetastatic, castrate-resistant prostate cancer to monthly subcutaneous denosumab 120 mg or placebo. Bone metastases were detected by bone scan and confirmed by scintigraphy.

"[This is] the first randomized study to demonstrate that targeting bone micro-environment prevents bone metastasis in men with prostate cancer."

The men were at high risk of developing bone metastasis as defined by a PSA of 8.0 ng/mL for 3 months prior to randomization or a PSA doubling time of 10 months or less. These dual PSA risk factors were present in 48% of the men. At least one-third of the men had a Gleason score of 8 or more at diagnosis.

The median time from diagnosis was 6 years and duration of androgen-deprivation therapy 4 years, said Dr. Oudard, chief of oncology at Georges Pompidou Hospital in Paris.

Denosumab significantly delayed the time to symptomatic bone metastases (HR, 0.67; P = .01), which translates into a 33% relative risk reduction. Similar benefits were observed for this end point across all disease and patient demographic characteristics, he said.

The overall results of the trial were reported earlier this year at the American Urological Association meeting. Despite delaying bone metastases, patients taking denosumab did not live longer than did those given placebo. Median overall survival was approximately 44 months in both groups (HR, 1.01; P = .91).

Serious adverse event rates were nearly identical at 46% in each arm; hypocalcemia was higher in the denosumab group at 1.7% vs. 0.3% with placebo. Another side effect, osteonecrosis of the jaw, was also slightly increased with denosumab at a cumulative incidence of 1.1% in year 1, 2.9% in year 2, and 4.2% in year 3 vs. 0% for all three years in the placebo group, Dr. Oudard said at the meeting, a joint congress of the European Cancer Organization, the European Society for Medical Oncology, and the European Society for Radiotherapy and Oncology.

Invited discussant Dr. Joaquim Bellmunt, with Hospital Valle de Hebron in Barcelona, said delaying the development of bone metastasis in men with castrate-resistant prostate cancer represents an important unmet medical need, and that screening for bone metastasis is often inadequate in clinical practice.

He went on to say that long-term quality of life data are needed, since the study showed only that denosumab prolongs the period before metastasis, where the patients’ quality of life has not yet suffered to a great extent.

Finally, Dr. Bellmunt took issue with the lack of survival benefit with denosumab, observing that patients with bone metastases have an almost five-time higher risk of death compared with those patients without.

Prevention of skeletal-related events and pain control are important in multimodality treatment of bone metastasis, he said, but "I want to stress that survival and quality of life is critical in these patients."

The study was funded by Amgen Inc. Disclosures were not presented at the meeting.

Christine Kilgore contributed to this report.

STOCKHOLM – Denosumab prolongs bone metastasis-free survival across a variety of nonmetastatic, castrate-resistant prostate cancer subgroups, according to subanalyses of a phase III study.

Denosumab (Xgeva) improved bone metastasis-free survival compared with placebo in men with dual prostate-specific antigen risk factors (hazard ratio, 0.83; P = .07), a single PSA risk factor (HR, 0.87; P = .20), a Gleason score of 2-7 (HR, 0.85, P = .12), and Gleason score of 8-10 (HR, 0.81; P = .10).

The advantage with denosumab was observed regardless of patient age, geographic region, or race, Dr. Stephane Oudard said at the European Multidisciplinary Cancer Congress.

Overall, the primary end point of bone metastasis-free survival was increased from 25.2 months with placebo to 29.5 months with denosumab. This corresponds to a relative risk reduction of 15% (hazard ratio, 0.85; P = .028).

Dr. Oudard pointed out that nearly all men with prostate cancer develop bone metastases, and that this is "the first randomized study to demonstrate that targeting bone microenvironment prevents bone metastasis in men with prostate cancer."

Denosumab is a monoclonal antibody that inhibits RANK ligand, a key mediator of bone osteoclast activity. The drug was approved in 2010 for the treatment of postmenopausal osteoporosis under the trade name Prolia, and later that year for the prevention of skeletal-related events in patients with bone metastases from solid tumors.

In September 2011, two new indications were added for denosumab: to increase bone mass in patients at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer, or adjuvant aromatase inhibitor therapy for breast cancer.

The phase III denosumab 147 study evenly randomized 1,432 men with nonmetastatic, castrate-resistant prostate cancer to monthly subcutaneous denosumab 120 mg or placebo. Bone metastases were detected by bone scan and confirmed by scintigraphy.

"[This is] the first randomized study to demonstrate that targeting bone micro-environment prevents bone metastasis in men with prostate cancer."

The men were at high risk of developing bone metastasis as defined by a PSA of 8.0 ng/mL for 3 months prior to randomization or a PSA doubling time of 10 months or less. These dual PSA risk factors were present in 48% of the men. At least one-third of the men had a Gleason score of 8 or more at diagnosis.

The median time from diagnosis was 6 years and duration of androgen-deprivation therapy 4 years, said Dr. Oudard, chief of oncology at Georges Pompidou Hospital in Paris.

Denosumab significantly delayed the time to symptomatic bone metastases (HR, 0.67; P = .01), which translates into a 33% relative risk reduction. Similar benefits were observed for this end point across all disease and patient demographic characteristics, he said.

The overall results of the trial were reported earlier this year at the American Urological Association meeting. Despite delaying bone metastases, patients taking denosumab did not live longer than did those given placebo. Median overall survival was approximately 44 months in both groups (HR, 1.01; P = .91).

Serious adverse event rates were nearly identical at 46% in each arm; hypocalcemia was higher in the denosumab group at 1.7% vs. 0.3% with placebo. Another side effect, osteonecrosis of the jaw, was also slightly increased with denosumab at a cumulative incidence of 1.1% in year 1, 2.9% in year 2, and 4.2% in year 3 vs. 0% for all three years in the placebo group, Dr. Oudard said at the meeting, a joint congress of the European Cancer Organization, the European Society for Medical Oncology, and the European Society for Radiotherapy and Oncology.

Invited discussant Dr. Joaquim Bellmunt, with Hospital Valle de Hebron in Barcelona, said delaying the development of bone metastasis in men with castrate-resistant prostate cancer represents an important unmet medical need, and that screening for bone metastasis is often inadequate in clinical practice.

He went on to say that long-term quality of life data are needed, since the study showed only that denosumab prolongs the period before metastasis, where the patients’ quality of life has not yet suffered to a great extent.

Finally, Dr. Bellmunt took issue with the lack of survival benefit with denosumab, observing that patients with bone metastases have an almost five-time higher risk of death compared with those patients without.

Prevention of skeletal-related events and pain control are important in multimodality treatment of bone metastasis, he said, but "I want to stress that survival and quality of life is critical in these patients."

The study was funded by Amgen Inc. Disclosures were not presented at the meeting.

Christine Kilgore contributed to this report.

STOCKHOLM – Denosumab prolongs bone metastasis-free survival across a variety of nonmetastatic, castrate-resistant prostate cancer subgroups, according to subanalyses of a phase III study.

Denosumab (Xgeva) improved bone metastasis-free survival compared with placebo in men with dual prostate-specific antigen risk factors (hazard ratio, 0.83; P = .07), a single PSA risk factor (HR, 0.87; P = .20), a Gleason score of 2-7 (HR, 0.85, P = .12), and Gleason score of 8-10 (HR, 0.81; P = .10).

The advantage with denosumab was observed regardless of patient age, geographic region, or race, Dr. Stephane Oudard said at the European Multidisciplinary Cancer Congress.

Overall, the primary end point of bone metastasis-free survival was increased from 25.2 months with placebo to 29.5 months with denosumab. This corresponds to a relative risk reduction of 15% (hazard ratio, 0.85; P = .028).

Dr. Oudard pointed out that nearly all men with prostate cancer develop bone metastases, and that this is "the first randomized study to demonstrate that targeting bone microenvironment prevents bone metastasis in men with prostate cancer."

Denosumab is a monoclonal antibody that inhibits RANK ligand, a key mediator of bone osteoclast activity. The drug was approved in 2010 for the treatment of postmenopausal osteoporosis under the trade name Prolia, and later that year for the prevention of skeletal-related events in patients with bone metastases from solid tumors.

In September 2011, two new indications were added for denosumab: to increase bone mass in patients at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer, or adjuvant aromatase inhibitor therapy for breast cancer.

The phase III denosumab 147 study evenly randomized 1,432 men with nonmetastatic, castrate-resistant prostate cancer to monthly subcutaneous denosumab 120 mg or placebo. Bone metastases were detected by bone scan and confirmed by scintigraphy.

"[This is] the first randomized study to demonstrate that targeting bone micro-environment prevents bone metastasis in men with prostate cancer."

The men were at high risk of developing bone metastasis as defined by a PSA of 8.0 ng/mL for 3 months prior to randomization or a PSA doubling time of 10 months or less. These dual PSA risk factors were present in 48% of the men. At least one-third of the men had a Gleason score of 8 or more at diagnosis.

The median time from diagnosis was 6 years and duration of androgen-deprivation therapy 4 years, said Dr. Oudard, chief of oncology at Georges Pompidou Hospital in Paris.

Denosumab significantly delayed the time to symptomatic bone metastases (HR, 0.67; P = .01), which translates into a 33% relative risk reduction. Similar benefits were observed for this end point across all disease and patient demographic characteristics, he said.

The overall results of the trial were reported earlier this year at the American Urological Association meeting. Despite delaying bone metastases, patients taking denosumab did not live longer than did those given placebo. Median overall survival was approximately 44 months in both groups (HR, 1.01; P = .91).

Serious adverse event rates were nearly identical at 46% in each arm; hypocalcemia was higher in the denosumab group at 1.7% vs. 0.3% with placebo. Another side effect, osteonecrosis of the jaw, was also slightly increased with denosumab at a cumulative incidence of 1.1% in year 1, 2.9% in year 2, and 4.2% in year 3 vs. 0% for all three years in the placebo group, Dr. Oudard said at the meeting, a joint congress of the European Cancer Organization, the European Society for Medical Oncology, and the European Society for Radiotherapy and Oncology.

Invited discussant Dr. Joaquim Bellmunt, with Hospital Valle de Hebron in Barcelona, said delaying the development of bone metastasis in men with castrate-resistant prostate cancer represents an important unmet medical need, and that screening for bone metastasis is often inadequate in clinical practice.

He went on to say that long-term quality of life data are needed, since the study showed only that denosumab prolongs the period before metastasis, where the patients’ quality of life has not yet suffered to a great extent.

Finally, Dr. Bellmunt took issue with the lack of survival benefit with denosumab, observing that patients with bone metastases have an almost five-time higher risk of death compared with those patients without.

Prevention of skeletal-related events and pain control are important in multimodality treatment of bone metastasis, he said, but "I want to stress that survival and quality of life is critical in these patients."

The study was funded by Amgen Inc. Disclosures were not presented at the meeting.

Christine Kilgore contributed to this report.

Overall, the American health care system improved its palliative care grade from a "C" to a "B," according to the study America’s Care of Serious Illness: a State-by-State Report Card on Access to Palliative Care in Our Nation’s Hospitals.

However, location impacts access to palliative care. The District of Columbia and seven other states – Maryland, Minnesota, Nebraska, Oregon, Rhode Island, Vermont, and Washington – earned "A" grades, while Delaware and Mississippi received "F" grades. Hospitals with palliative care programs are currently less common in the South as well as in hospitals with fewer than 50 beds.

The findings were based on data collected by the Center to Advance Palliative Care (CAPC) and the National Palliative Care Research Center (NPCRC).

The data showed that 85% of hospitals with 300 or more beds had palliative care teams, compared with 54% of public hospitals, 37% of sole community provider hospitals, and 26% of for-profit hospitals. Hospitals with 50 or more beds are more likely to be not-for-profit, and thus are more likely to offer palliative care.

The number of states earning an "A" grade improved from only three states in 2008 to seven states plus the District of Columbia in 2011. But the lack of palliative medicine physicians remains a major barrier to the continued improvement of palliative care in the U.S., where there is currently one palliative care physician for every 1,200 individuals living with a serious or life-threatening condition, the researchers noted.

"Focused efforts by hospital administration, the health care community, and policymakers are required to promote the development of quality palliative care programs in all hospitals, with special attention needed in small, rural, public, and for-profit hospitals," the CAPC said in a press release accompanying the report.

Overall, the American health care system improved its palliative care grade from a "C" to a "B," according to the study America’s Care of Serious Illness: a State-by-State Report Card on Access to Palliative Care in Our Nation’s Hospitals.

However, location impacts access to palliative care. The District of Columbia and seven other states – Maryland, Minnesota, Nebraska, Oregon, Rhode Island, Vermont, and Washington – earned "A" grades, while Delaware and Mississippi received "F" grades. Hospitals with palliative care programs are currently less common in the South as well as in hospitals with fewer than 50 beds.

The findings were based on data collected by the Center to Advance Palliative Care (CAPC) and the National Palliative Care Research Center (NPCRC).

The data showed that 85% of hospitals with 300 or more beds had palliative care teams, compared with 54% of public hospitals, 37% of sole community provider hospitals, and 26% of for-profit hospitals. Hospitals with 50 or more beds are more likely to be not-for-profit, and thus are more likely to offer palliative care.

The number of states earning an "A" grade improved from only three states in 2008 to seven states plus the District of Columbia in 2011. But the lack of palliative medicine physicians remains a major barrier to the continued improvement of palliative care in the U.S., where there is currently one palliative care physician for every 1,200 individuals living with a serious or life-threatening condition, the researchers noted.

"Focused efforts by hospital administration, the health care community, and policymakers are required to promote the development of quality palliative care programs in all hospitals, with special attention needed in small, rural, public, and for-profit hospitals," the CAPC said in a press release accompanying the report.

Overall, the American health care system improved its palliative care grade from a "C" to a "B," according to the study America’s Care of Serious Illness: a State-by-State Report Card on Access to Palliative Care in Our Nation’s Hospitals.

However, location impacts access to palliative care. The District of Columbia and seven other states – Maryland, Minnesota, Nebraska, Oregon, Rhode Island, Vermont, and Washington – earned "A" grades, while Delaware and Mississippi received "F" grades. Hospitals with palliative care programs are currently less common in the South as well as in hospitals with fewer than 50 beds.

The findings were based on data collected by the Center to Advance Palliative Care (CAPC) and the National Palliative Care Research Center (NPCRC).

The data showed that 85% of hospitals with 300 or more beds had palliative care teams, compared with 54% of public hospitals, 37% of sole community provider hospitals, and 26% of for-profit hospitals. Hospitals with 50 or more beds are more likely to be not-for-profit, and thus are more likely to offer palliative care.

The number of states earning an "A" grade improved from only three states in 2008 to seven states plus the District of Columbia in 2011. But the lack of palliative medicine physicians remains a major barrier to the continued improvement of palliative care in the U.S., where there is currently one palliative care physician for every 1,200 individuals living with a serious or life-threatening condition, the researchers noted.

"Focused efforts by hospital administration, the health care community, and policymakers are required to promote the development of quality palliative care programs in all hospitals, with special attention needed in small, rural, public, and for-profit hospitals," the CAPC said in a press release accompanying the report.

WASHINGTON – A combination of risk factors may be driving a large increase in liver cancer among Latinos in the United States, researchers said at a conference sponsored by the American Association for Cancer Research.

Although liver cancer, or hepatocellular carcinoma (HCC), is most common in Asia and Africa, the incidence is on the rise in the United States, primarily due to hepatitis C virus infection. There are 20,000 new HCC cases in this country each year, and liver cancer is the fifth most common cancer in men and the seventh most common in women, according to a recent review article in the New England Journal of Medicine (2011;365:1118-27).

The main risk factors for HCC in Africa and Asia have been infection with hepatitis B or hepatitis C, and alcoholic liver disease. More recently, evidence has suggested that fatty liver disease and metabolic syndrome may be significant risk factors in Western countries, according to the NEJM review.

In the United States, HCC incidence was 1.7 cases per 100,000 in 1980, but by 2005, this figure had increased to 5 per 100,000, noted the lead author of the Texas study, Amelie Ramirez, Dr.P.H., who presented the data at the conference. Dr. Ramirez, director of the Institute for Health Promotion Research at the University of Texas Health Science Center at San Antonio, and her colleagues decided to see if they could tease out some risk factors for HCC and thereby help to explain the increase among Latinos living in that state.

The investigators used data from the U.S. Surveillance, Epidemiology, and End Results (SEER) program, the Texas Cancer Registry, and the Texas Department of State Health Services. They examined the time period 1995-2006 and calculated age-adjusted and age-specific HCC incidence rates as well as the prevalence of obesity, diabetes, heavy alcohol use, and smoking.

Dr. Ramirez and her colleagues found that Latinos accounted for one third of HCC cases in Texas, and about 75% of cases in South Texas. The rates were 10.6 cases per 100,000 in South Texas and 9.7 per 100,000 in the state, compared with 7.5 per 100,000 among Latinos nationally in the SEER database. About 70% of cases were in men, an observation that held across all three populations – SEER, Texas, and South Texas.

Latinos are the fastest-growing U.S. minority group, accounting for 20% of the total U.S. population and 36% of the population of Texas; by the year 2030, Latinos will constitute a majority of Texas’ census, Dr. Ramirez noted (U.S. Census Bureau, 2010). This pattern is especially pronounced in South Texas, a large region that is currently almost 70% Latino.

The researchers also documented increases in the prevalence of obesity and diabetes among Texas and South Texas Latinos. When they analyzed the time periods 1995-1997 and 2004-2006 separately, the researchers found that obesity for all Latinos increased. During 2004-2006, Texas and South Texas Latinos had higher rates of obesity than U.S. Latinos overall. For U.S. Latinos, the obesity rate was 27%, compared with 30% for Texas Latinos and 35% for South Texas Latinos.

Diabetes prevalence also increased among U.S. Latinos overall, while the prevalence figures for South Texas and Texas Latinos showed increases, but they were not significant.

Heavy alcohol use and smoking did not appear to be significant risk factors for HCC in the analyses. However, the study shows that obesity and diabetes, both of which are preventable and treatable, should receive more attention in the Latino population, especially in Texas, Dr. Ramirez said.

WASHINGTON – A combination of risk factors may be driving a large increase in liver cancer among Latinos in the United States, researchers said at a conference sponsored by the American Association for Cancer Research.

Although liver cancer, or hepatocellular carcinoma (HCC), is most common in Asia and Africa, the incidence is on the rise in the United States, primarily due to hepatitis C virus infection. There are 20,000 new HCC cases in this country each year, and liver cancer is the fifth most common cancer in men and the seventh most common in women, according to a recent review article in the New England Journal of Medicine (2011;365:1118-27).

The main risk factors for HCC in Africa and Asia have been infection with hepatitis B or hepatitis C, and alcoholic liver disease. More recently, evidence has suggested that fatty liver disease and metabolic syndrome may be significant risk factors in Western countries, according to the NEJM review.

In the United States, HCC incidence was 1.7 cases per 100,000 in 1980, but by 2005, this figure had increased to 5 per 100,000, noted the lead author of the Texas study, Amelie Ramirez, Dr.P.H., who presented the data at the conference. Dr. Ramirez, director of the Institute for Health Promotion Research at the University of Texas Health Science Center at San Antonio, and her colleagues decided to see if they could tease out some risk factors for HCC and thereby help to explain the increase among Latinos living in that state.

The investigators used data from the U.S. Surveillance, Epidemiology, and End Results (SEER) program, the Texas Cancer Registry, and the Texas Department of State Health Services. They examined the time period 1995-2006 and calculated age-adjusted and age-specific HCC incidence rates as well as the prevalence of obesity, diabetes, heavy alcohol use, and smoking.

Dr. Ramirez and her colleagues found that Latinos accounted for one third of HCC cases in Texas, and about 75% of cases in South Texas. The rates were 10.6 cases per 100,000 in South Texas and 9.7 per 100,000 in the state, compared with 7.5 per 100,000 among Latinos nationally in the SEER database. About 70% of cases were in men, an observation that held across all three populations – SEER, Texas, and South Texas.

Latinos are the fastest-growing U.S. minority group, accounting for 20% of the total U.S. population and 36% of the population of Texas; by the year 2030, Latinos will constitute a majority of Texas’ census, Dr. Ramirez noted (U.S. Census Bureau, 2010). This pattern is especially pronounced in South Texas, a large region that is currently almost 70% Latino.

The researchers also documented increases in the prevalence of obesity and diabetes among Texas and South Texas Latinos. When they analyzed the time periods 1995-1997 and 2004-2006 separately, the researchers found that obesity for all Latinos increased. During 2004-2006, Texas and South Texas Latinos had higher rates of obesity than U.S. Latinos overall. For U.S. Latinos, the obesity rate was 27%, compared with 30% for Texas Latinos and 35% for South Texas Latinos.

Diabetes prevalence also increased among U.S. Latinos overall, while the prevalence figures for South Texas and Texas Latinos showed increases, but they were not significant.

Heavy alcohol use and smoking did not appear to be significant risk factors for HCC in the analyses. However, the study shows that obesity and diabetes, both of which are preventable and treatable, should receive more attention in the Latino population, especially in Texas, Dr. Ramirez said.

WASHINGTON – A combination of risk factors may be driving a large increase in liver cancer among Latinos in the United States, researchers said at a conference sponsored by the American Association for Cancer Research.

Although liver cancer, or hepatocellular carcinoma (HCC), is most common in Asia and Africa, the incidence is on the rise in the United States, primarily due to hepatitis C virus infection. There are 20,000 new HCC cases in this country each year, and liver cancer is the fifth most common cancer in men and the seventh most common in women, according to a recent review article in the New England Journal of Medicine (2011;365:1118-27).

The main risk factors for HCC in Africa and Asia have been infection with hepatitis B or hepatitis C, and alcoholic liver disease. More recently, evidence has suggested that fatty liver disease and metabolic syndrome may be significant risk factors in Western countries, according to the NEJM review.

In the United States, HCC incidence was 1.7 cases per 100,000 in 1980, but by 2005, this figure had increased to 5 per 100,000, noted the lead author of the Texas study, Amelie Ramirez, Dr.P.H., who presented the data at the conference. Dr. Ramirez, director of the Institute for Health Promotion Research at the University of Texas Health Science Center at San Antonio, and her colleagues decided to see if they could tease out some risk factors for HCC and thereby help to explain the increase among Latinos living in that state.

The investigators used data from the U.S. Surveillance, Epidemiology, and End Results (SEER) program, the Texas Cancer Registry, and the Texas Department of State Health Services. They examined the time period 1995-2006 and calculated age-adjusted and age-specific HCC incidence rates as well as the prevalence of obesity, diabetes, heavy alcohol use, and smoking.

Dr. Ramirez and her colleagues found that Latinos accounted for one third of HCC cases in Texas, and about 75% of cases in South Texas. The rates were 10.6 cases per 100,000 in South Texas and 9.7 per 100,000 in the state, compared with 7.5 per 100,000 among Latinos nationally in the SEER database. About 70% of cases were in men, an observation that held across all three populations – SEER, Texas, and South Texas.

Latinos are the fastest-growing U.S. minority group, accounting for 20% of the total U.S. population and 36% of the population of Texas; by the year 2030, Latinos will constitute a majority of Texas’ census, Dr. Ramirez noted (U.S. Census Bureau, 2010). This pattern is especially pronounced in South Texas, a large region that is currently almost 70% Latino.

The researchers also documented increases in the prevalence of obesity and diabetes among Texas and South Texas Latinos. When they analyzed the time periods 1995-1997 and 2004-2006 separately, the researchers found that obesity for all Latinos increased. During 2004-2006, Texas and South Texas Latinos had higher rates of obesity than U.S. Latinos overall. For U.S. Latinos, the obesity rate was 27%, compared with 30% for Texas Latinos and 35% for South Texas Latinos.

Diabetes prevalence also increased among U.S. Latinos overall, while the prevalence figures for South Texas and Texas Latinos showed increases, but they were not significant.

Heavy alcohol use and smoking did not appear to be significant risk factors for HCC in the analyses. However, the study shows that obesity and diabetes, both of which are preventable and treatable, should receive more attention in the Latino population, especially in Texas, Dr. Ramirez said.

Join Community Oncology Editor David Henry as he reviews 10 tips for implementing quality improvement, what oncologists need to know about direct-to-consumer genetic testing, an analysis of value-based reimbursement, and a practical biostatistics approach to counting what really counts in the irinotecan in recurrent glioblastoma trial results.

Join Community Oncology Editor David Henry as he reviews 10 tips for implementing quality improvement, what oncologists need to know about direct-to-consumer genetic testing, an analysis of value-based reimbursement, and a practical biostatistics approach to counting what really counts in the irinotecan in recurrent glioblastoma trial results.

Join Community Oncology Editor David Henry as he reviews 10 tips for implementing quality improvement, what oncologists need to know about direct-to-consumer genetic testing, an analysis of value-based reimbursement, and a practical biostatistics approach to counting what really counts in the irinotecan in recurrent glioblastoma trial results.

The Journal of Supportive Oncology
Volume 9, Issue 4, July-August 2011, Pages 127-128
doi:10.1016/j.suponc.2011.04.006 | Permissions & Reprints

Available online 2 July 2011.

Peer Viewpoint

Does One Size Fit All? Is There a Standard Radiation Dose for Malignant Spinal Cord Compression?

Ramachandran Venkitaraman MD, MRCP, FRCR

Commentary on “The Optimal Dose Fractionation Schema for Malignant Extradural Spinal Cord Compression" by D. Andrew Loblaw and Gunita Mitera (page 123).

In this edition of the Journal of Supportive Oncology, Loblaw and Mitera have published a succinct review of trials of radiotherapy (RT) dose schedules for treating malignant spinal cord compression (MSCC). Treatment options for MSCC include surgery and RT, with the latter being the most commonly utilized option as the majority of patients are unfit to undergo surgery. This concise review of RT dose for spinal cord compression sheds light in an area where there are very few randomized controlled trials. Clinicians have historically favored multiple fraction regimens for treating patients with MSCC. The most common regimes are either 20 Gy in five fractions or 30 Gy in 10 fractions, with a single fraction of 8 Gy mainly reserved for patients with a poor performance status. Prospective studies suggest a different set of prognostic factors for deciding the dose of RT in these patients.

The histology of the primary tumor is one of the important predictive factors for outcome. Patients with myeloma, breast, prostate, and thyroid malignancies have a favorable outcome. The survival rate for patients with tumors such as lung, melanoma, and sarcoma is generally dismal.^[1] Mainly, primary tumors that are very sensitive to RT are lymphomas, myeloma, and seminomatous germ-cell tumors, as well as breast and prostate cancers. Gastrointestinal tract cancer, lung cancer, renal tumors, sarcomas, and gynecological tumors are considered to have poor radiosensitivity.

Randomized trials, especially in patients with unfavorable tumor histology, do not show any superiority for fractionated treatments compared to a single fraction of 8 Gy. ^{[2] , [3] and [4]} Single-fraction RT is advantageous in terms of time, cost, resources, and patient comfort. It should be considered as the standard dose for patients with extensive metastatic disease and a life expectancy of less than six months and for less radiosensitive primary tumors such as lung, melanoma, and sarcoma.

In patients with favorable histology, retrospective and nonrandomized evidence suggests a trend toward superiority of the higher fractionation schedules in terms of benefit in local control, with fewer in-field recurrences. ^{[1] , [5] , [6] , [7] and [8]} In the prospective SCORE-1 study, there was a statistically significant improved progression-free survival (72% at 12 months after long-course and 55% after short-course RT, P = 0.034) and local control (12-month local control rate, 77% after long-course and 61% after short-course RT, P = 0.032).5 With the ever-improving systemic treatment options for malignancies and the survival of these patients with metastatic disease showing an incremental increase with each decade, preventing recurrence of spinal cord compression becomes even more important. Long-course RT with doses of 30 Gy in 10 fractions offers no benefit compared to shorter regimens in terms of survival. However, long-course RT appears to improve local control, and there are fewer in-field recurrences, which would be an advantage in patients with favorable histology.^[5] The longer schedule of RT, 30 Gy in 10 fractions, should also be considered in the postoperative setting, subject to recovery from the surgery. There is no practical advantage in offering treatments greater or longer than 30 Gy in 10 fractions in any patient subgroup.^[9]

Similarly, in retrospective studies, for patients with limited metastases who are expected to live longer, survival is associated with tumor type, ambulatory status, slower development of motor deficits, and long-course RT.^[10] The six factors demonstrated on multivariate analysis to be significant for survival outcome by Rades et al1 are primary tumor histology, visceral metastases, other extensive bone metastases, ambulatory status before RT, interval between tumor diagnosis and MSCC, and length of time in developing motor deficits. RT dose does not appear to affect the outcome in patients with low scores on these prognostic systems, while a longer-course RT may be effective in patients scoring highly.1

As recommended in the review article by Loblaw and Mitera, risk stratification of patients with MSCC is essential for deciding the dose of RT. A single fraction of 8 Gy is ideal for patients with poor prognostic factors. Randomized controlled trials of single vs. multifractionated treatments, similar to the SCORAD trial, determine the optimal dose-fractionation schedule of RT for MSCC with favorable prognostic factors.

References [PubMed ID in brackets]

1 D. Rades, F. Fehlauer, R. Schulte, T. Veninga, L.J. Stalpers, H. Basic, A. Bajrovic, P.J. Hoskin, S. Tribius, I. Wildfang, V. Rudat, R. Engenhart-Cabilic, J.H. Karstens, W. Alberti, J. Dunst and S.E. Schild, Prognostic factors for local control and survival after radiotherapy of metastatic spinal cord compression. J Clin Oncol,  24 21 (2006), pp. 3388–3393.

2 E. Maranzano, P. Latini, S. Beneventi, L. Marafioti, F. Piro, E. Perrucci and M. Lupattelli, Comparison of two different radiotherapy schedules for spinal cord compression in prostate cancer. Tumori,  84 4 (1998), pp. 472–477.

3 E. Maranzano, R. Bellavita, R. Rossi, V. De Angelis, A. Frattegiani, R. Bagnoli, M. Mignogna, S. Beneventi, M. Lupattelli, P. Ponticelli, G.P. Biti and P. Latini, Short-course versus split-course radiotherapy in metastatic spinal cord compression: results of a phase III, randomized, multicenter trial. J Clin Oncol,  23 15 (2005), pp. 3358–3365.

4 E. Maranzano, F. Trippa, M. Casale, S. Costantini, M. Lupattelli, R. Bellavita, L. Marafioti, S. Pergolizzi, A. Santacaterina, M. Mignogna, G. Silvano and V. Fusco, 8Gy single-dose radiotherapy is effective in metastatic spinal cord compression: results of a phase III randomized multicentre Italian trial. Radiother Oncol,  93 2 (2009), pp. 174–179.

5 D. Rades, M. Lange, T. Veninga, V. Rudat, A. Bajrovic, L.J. Stalpers, J. Dunst and S.E. Schild, Preliminary results of spinal cord compression recurrence evaluation (score-1) study comparing short-course versus long-course radiotherapy for local control of malignant epidural spinal cord compression. Int J Radiat Oncol Biol Phys,  73 1 (2009), pp. 228–234.

6 D. Rades, P.J. Hoskin, L.J. Stalpers, R. Schulte, P. Poortmans, T. Veninga, J. Dahm-Daphi, N. Obralic, I. Wildfang, R. Bahrehmand, R. Engenhart-Cabilic and S.E. Schild, Short-course radiotherapy is not optimal for spinal cord compression due to myeloma. Int J Radiat Oncol Biol Phys,  64 5 (2006), pp. 1452–1457.

7 D. Rades, L.J. Stalpers, T. Veninga, V. Rudat, R. Schulte and P.J. Hoskin, Evaluation of functional outcome and local control after radiotherapy for metastatic spinal cord compression in patients with prostate cancer. J Urol,  175 2 (2006), pp. 552–556.

8 D. Rades, T. Veninga, L.J. Stalpers, R. Schulte, P.J. Hoskin, P. Poortmans, S.E. Schild and V. Rudat, Prognostic factors predicting functional outcomes, recurrence-free survival, and overall survival after radiotherapy for metastatic spinal cord compression in breast cancer patients. Int J Radiat Oncol Biol Phys,  64 1 (2006), pp. 182–188.

9 D. Rades, F. Fehlauer, L.J. Stalpers, I. Wildfang, O. Zschenker, S.E. Schild, H.J. Schmoll, J.H. Karstens and W. Alberti, A prospective evaluation of two radiotherapy schedules with 10 versus 20 fractions for the treatment of metastatic spinal cord compression: final results of a multicenter study. Cancer,  101 11 (2004), pp. 2687–2692.

10 D. Rades, T. Veninga, L.J. Stalpers, H. Basic, V. Rudat, J.H. Karstens, J. Dunst and S.E. Schild, Outcome after radiotherapy alone for metastatic spinal cord compression in patients with oligometastases. J Clin Oncol,  25 1 (2007), pp. 50–56.

Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Correspondence to: Ramachandran Venkitaraman, MD, MRCP, FRCR, Suffolk Oncology Centre, Ipswich Hospital NHS, Heath Road, Ipswich, IP4 5PD, UK; telephone: (0044) 1473704177; fax: (0044) 1473704916

Author Vitae
Dr. Venkitaraman is Consultant Clinical Oncologist, Suffolk Oncology Centre, Ipswich Hospital NHS, Ipswich, United Kingdom.

The Journal of Supportive Oncology
Volume 9, Issue 4, July-August 2011, Pages 127-128
doi:10.1016/j.suponc.2011.04.006 | Permissions & Reprints

Available online 2 July 2011.

Peer Viewpoint

Does One Size Fit All? Is There a Standard Radiation Dose for Malignant Spinal Cord Compression?

Ramachandran Venkitaraman MD, MRCP, FRCR

Commentary on “The Optimal Dose Fractionation Schema for Malignant Extradural Spinal Cord Compression" by D. Andrew Loblaw and Gunita Mitera (page 123).

In this edition of the Journal of Supportive Oncology, Loblaw and Mitera have published a succinct review of trials of radiotherapy (RT) dose schedules for treating malignant spinal cord compression (MSCC). Treatment options for MSCC include surgery and RT, with the latter being the most commonly utilized option as the majority of patients are unfit to undergo surgery. This concise review of RT dose for spinal cord compression sheds light in an area where there are very few randomized controlled trials. Clinicians have historically favored multiple fraction regimens for treating patients with MSCC. The most common regimes are either 20 Gy in five fractions or 30 Gy in 10 fractions, with a single fraction of 8 Gy mainly reserved for patients with a poor performance status. Prospective studies suggest a different set of prognostic factors for deciding the dose of RT in these patients.

The histology of the primary tumor is one of the important predictive factors for outcome. Patients with myeloma, breast, prostate, and thyroid malignancies have a favorable outcome. The survival rate for patients with tumors such as lung, melanoma, and sarcoma is generally dismal.^[1] Mainly, primary tumors that are very sensitive to RT are lymphomas, myeloma, and seminomatous germ-cell tumors, as well as breast and prostate cancers. Gastrointestinal tract cancer, lung cancer, renal tumors, sarcomas, and gynecological tumors are considered to have poor radiosensitivity.

Randomized trials, especially in patients with unfavorable tumor histology, do not show any superiority for fractionated treatments compared to a single fraction of 8 Gy. ^{[2] , [3] and [4]} Single-fraction RT is advantageous in terms of time, cost, resources, and patient comfort. It should be considered as the standard dose for patients with extensive metastatic disease and a life expectancy of less than six months and for less radiosensitive primary tumors such as lung, melanoma, and sarcoma.

In patients with favorable histology, retrospective and nonrandomized evidence suggests a trend toward superiority of the higher fractionation schedules in terms of benefit in local control, with fewer in-field recurrences. ^{[1] , [5] , [6] , [7] and [8]} In the prospective SCORE-1 study, there was a statistically significant improved progression-free survival (72% at 12 months after long-course and 55% after short-course RT, P = 0.034) and local control (12-month local control rate, 77% after long-course and 61% after short-course RT, P = 0.032).5 With the ever-improving systemic treatment options for malignancies and the survival of these patients with metastatic disease showing an incremental increase with each decade, preventing recurrence of spinal cord compression becomes even more important. Long-course RT with doses of 30 Gy in 10 fractions offers no benefit compared to shorter regimens in terms of survival. However, long-course RT appears to improve local control, and there are fewer in-field recurrences, which would be an advantage in patients with favorable histology.^[5] The longer schedule of RT, 30 Gy in 10 fractions, should also be considered in the postoperative setting, subject to recovery from the surgery. There is no practical advantage in offering treatments greater or longer than 30 Gy in 10 fractions in any patient subgroup.^[9]

Similarly, in retrospective studies, for patients with limited metastases who are expected to live longer, survival is associated with tumor type, ambulatory status, slower development of motor deficits, and long-course RT.^[10] The six factors demonstrated on multivariate analysis to be significant for survival outcome by Rades et al1 are primary tumor histology, visceral metastases, other extensive bone metastases, ambulatory status before RT, interval between tumor diagnosis and MSCC, and length of time in developing motor deficits. RT dose does not appear to affect the outcome in patients with low scores on these prognostic systems, while a longer-course RT may be effective in patients scoring highly.1

As recommended in the review article by Loblaw and Mitera, risk stratification of patients with MSCC is essential for deciding the dose of RT. A single fraction of 8 Gy is ideal for patients with poor prognostic factors. Randomized controlled trials of single vs. multifractionated treatments, similar to the SCORAD trial, determine the optimal dose-fractionation schedule of RT for MSCC with favorable prognostic factors.

References [PubMed ID in brackets]

1 D. Rades, F. Fehlauer, R. Schulte, T. Veninga, L.J. Stalpers, H. Basic, A. Bajrovic, P.J. Hoskin, S. Tribius, I. Wildfang, V. Rudat, R. Engenhart-Cabilic, J.H. Karstens, W. Alberti, J. Dunst and S.E. Schild, Prognostic factors for local control and survival after radiotherapy of metastatic spinal cord compression. J Clin Oncol,  24 21 (2006), pp. 3388–3393.

2 E. Maranzano, P. Latini, S. Beneventi, L. Marafioti, F. Piro, E. Perrucci and M. Lupattelli, Comparison of two different radiotherapy schedules for spinal cord compression in prostate cancer. Tumori,  84 4 (1998), pp. 472–477.

3 E. Maranzano, R. Bellavita, R. Rossi, V. De Angelis, A. Frattegiani, R. Bagnoli, M. Mignogna, S. Beneventi, M. Lupattelli, P. Ponticelli, G.P. Biti and P. Latini, Short-course versus split-course radiotherapy in metastatic spinal cord compression: results of a phase III, randomized, multicenter trial. J Clin Oncol,  23 15 (2005), pp. 3358–3365.

4 E. Maranzano, F. Trippa, M. Casale, S. Costantini, M. Lupattelli, R. Bellavita, L. Marafioti, S. Pergolizzi, A. Santacaterina, M. Mignogna, G. Silvano and V. Fusco, 8Gy single-dose radiotherapy is effective in metastatic spinal cord compression: results of a phase III randomized multicentre Italian trial. Radiother Oncol,  93 2 (2009), pp. 174–179.

5 D. Rades, M. Lange, T. Veninga, V. Rudat, A. Bajrovic, L.J. Stalpers, J. Dunst and S.E. Schild, Preliminary results of spinal cord compression recurrence evaluation (score-1) study comparing short-course versus long-course radiotherapy for local control of malignant epidural spinal cord compression. Int J Radiat Oncol Biol Phys,  73 1 (2009), pp. 228–234.

6 D. Rades, P.J. Hoskin, L.J. Stalpers, R. Schulte, P. Poortmans, T. Veninga, J. Dahm-Daphi, N. Obralic, I. Wildfang, R. Bahrehmand, R. Engenhart-Cabilic and S.E. Schild, Short-course radiotherapy is not optimal for spinal cord compression due to myeloma. Int J Radiat Oncol Biol Phys,  64 5 (2006), pp. 1452–1457.

7 D. Rades, L.J. Stalpers, T. Veninga, V. Rudat, R. Schulte and P.J. Hoskin, Evaluation of functional outcome and local control after radiotherapy for metastatic spinal cord compression in patients with prostate cancer. J Urol,  175 2 (2006), pp. 552–556.

8 D. Rades, T. Veninga, L.J. Stalpers, R. Schulte, P.J. Hoskin, P. Poortmans, S.E. Schild and V. Rudat, Prognostic factors predicting functional outcomes, recurrence-free survival, and overall survival after radiotherapy for metastatic spinal cord compression in breast cancer patients. Int J Radiat Oncol Biol Phys,  64 1 (2006), pp. 182–188.

9 D. Rades, F. Fehlauer, L.J. Stalpers, I. Wildfang, O. Zschenker, S.E. Schild, H.J. Schmoll, J.H. Karstens and W. Alberti, A prospective evaluation of two radiotherapy schedules with 10 versus 20 fractions for the treatment of metastatic spinal cord compression: final results of a multicenter study. Cancer,  101 11 (2004), pp. 2687–2692.

10 D. Rades, T. Veninga, L.J. Stalpers, H. Basic, V. Rudat, J.H. Karstens, J. Dunst and S.E. Schild, Outcome after radiotherapy alone for metastatic spinal cord compression in patients with oligometastases. J Clin Oncol,  25 1 (2007), pp. 50–56.

Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Correspondence to: Ramachandran Venkitaraman, MD, MRCP, FRCR, Suffolk Oncology Centre, Ipswich Hospital NHS, Heath Road, Ipswich, IP4 5PD, UK; telephone: (0044) 1473704177; fax: (0044) 1473704916

Author Vitae
Dr. Venkitaraman is Consultant Clinical Oncologist, Suffolk Oncology Centre, Ipswich Hospital NHS, Ipswich, United Kingdom.

The Journal of Supportive Oncology
Volume 9, Issue 4, July-August 2011, Pages 127-128
doi:10.1016/j.suponc.2011.04.006 | Permissions & Reprints

Available online 2 July 2011.

Peer Viewpoint

Does One Size Fit All? Is There a Standard Radiation Dose for Malignant Spinal Cord Compression?

Ramachandran Venkitaraman MD, MRCP, FRCR

Commentary on “The Optimal Dose Fractionation Schema for Malignant Extradural Spinal Cord Compression" by D. Andrew Loblaw and Gunita Mitera (page 123).

In this edition of the Journal of Supportive Oncology, Loblaw and Mitera have published a succinct review of trials of radiotherapy (RT) dose schedules for treating malignant spinal cord compression (MSCC). Treatment options for MSCC include surgery and RT, with the latter being the most commonly utilized option as the majority of patients are unfit to undergo surgery. This concise review of RT dose for spinal cord compression sheds light in an area where there are very few randomized controlled trials. Clinicians have historically favored multiple fraction regimens for treating patients with MSCC. The most common regimes are either 20 Gy in five fractions or 30 Gy in 10 fractions, with a single fraction of 8 Gy mainly reserved for patients with a poor performance status. Prospective studies suggest a different set of prognostic factors for deciding the dose of RT in these patients.

The histology of the primary tumor is one of the important predictive factors for outcome. Patients with myeloma, breast, prostate, and thyroid malignancies have a favorable outcome. The survival rate for patients with tumors such as lung, melanoma, and sarcoma is generally dismal.^[1] Mainly, primary tumors that are very sensitive to RT are lymphomas, myeloma, and seminomatous germ-cell tumors, as well as breast and prostate cancers. Gastrointestinal tract cancer, lung cancer, renal tumors, sarcomas, and gynecological tumors are considered to have poor radiosensitivity.

Randomized trials, especially in patients with unfavorable tumor histology, do not show any superiority for fractionated treatments compared to a single fraction of 8 Gy. ^{[2] , [3] and [4]} Single-fraction RT is advantageous in terms of time, cost, resources, and patient comfort. It should be considered as the standard dose for patients with extensive metastatic disease and a life expectancy of less than six months and for less radiosensitive primary tumors such as lung, melanoma, and sarcoma.

In patients with favorable histology, retrospective and nonrandomized evidence suggests a trend toward superiority of the higher fractionation schedules in terms of benefit in local control, with fewer in-field recurrences. ^{[1] , [5] , [6] , [7] and [8]} In the prospective SCORE-1 study, there was a statistically significant improved progression-free survival (72% at 12 months after long-course and 55% after short-course RT, P = 0.034) and local control (12-month local control rate, 77% after long-course and 61% after short-course RT, P = 0.032).5 With the ever-improving systemic treatment options for malignancies and the survival of these patients with metastatic disease showing an incremental increase with each decade, preventing recurrence of spinal cord compression becomes even more important. Long-course RT with doses of 30 Gy in 10 fractions offers no benefit compared to shorter regimens in terms of survival. However, long-course RT appears to improve local control, and there are fewer in-field recurrences, which would be an advantage in patients with favorable histology.^[5] The longer schedule of RT, 30 Gy in 10 fractions, should also be considered in the postoperative setting, subject to recovery from the surgery. There is no practical advantage in offering treatments greater or longer than 30 Gy in 10 fractions in any patient subgroup.^[9]

Similarly, in retrospective studies, for patients with limited metastases who are expected to live longer, survival is associated with tumor type, ambulatory status, slower development of motor deficits, and long-course RT.^[10] The six factors demonstrated on multivariate analysis to be significant for survival outcome by Rades et al1 are primary tumor histology, visceral metastases, other extensive bone metastases, ambulatory status before RT, interval between tumor diagnosis and MSCC, and length of time in developing motor deficits. RT dose does not appear to affect the outcome in patients with low scores on these prognostic systems, while a longer-course RT may be effective in patients scoring highly.1

As recommended in the review article by Loblaw and Mitera, risk stratification of patients with MSCC is essential for deciding the dose of RT. A single fraction of 8 Gy is ideal for patients with poor prognostic factors. Randomized controlled trials of single vs. multifractionated treatments, similar to the SCORAD trial, determine the optimal dose-fractionation schedule of RT for MSCC with favorable prognostic factors.

References [PubMed ID in brackets]

1 D. Rades, F. Fehlauer, R. Schulte, T. Veninga, L.J. Stalpers, H. Basic, A. Bajrovic, P.J. Hoskin, S. Tribius, I. Wildfang, V. Rudat, R. Engenhart-Cabilic, J.H. Karstens, W. Alberti, J. Dunst and S.E. Schild, Prognostic factors for local control and survival after radiotherapy of metastatic spinal cord compression. J Clin Oncol,  24 21 (2006), pp. 3388–3393.

2 E. Maranzano, P. Latini, S. Beneventi, L. Marafioti, F. Piro, E. Perrucci and M. Lupattelli, Comparison of two different radiotherapy schedules for spinal cord compression in prostate cancer. Tumori,  84 4 (1998), pp. 472–477.

3 E. Maranzano, R. Bellavita, R. Rossi, V. De Angelis, A. Frattegiani, R. Bagnoli, M. Mignogna, S. Beneventi, M. Lupattelli, P. Ponticelli, G.P. Biti and P. Latini, Short-course versus split-course radiotherapy in metastatic spinal cord compression: results of a phase III, randomized, multicenter trial. J Clin Oncol,  23 15 (2005), pp. 3358–3365.

4 E. Maranzano, F. Trippa, M. Casale, S. Costantini, M. Lupattelli, R. Bellavita, L. Marafioti, S. Pergolizzi, A. Santacaterina, M. Mignogna, G. Silvano and V. Fusco, 8Gy single-dose radiotherapy is effective in metastatic spinal cord compression: results of a phase III randomized multicentre Italian trial. Radiother Oncol,  93 2 (2009), pp. 174–179.

5 D. Rades, M. Lange, T. Veninga, V. Rudat, A. Bajrovic, L.J. Stalpers, J. Dunst and S.E. Schild, Preliminary results of spinal cord compression recurrence evaluation (score-1) study comparing short-course versus long-course radiotherapy for local control of malignant epidural spinal cord compression. Int J Radiat Oncol Biol Phys,  73 1 (2009), pp. 228–234.

6 D. Rades, P.J. Hoskin, L.J. Stalpers, R. Schulte, P. Poortmans, T. Veninga, J. Dahm-Daphi, N. Obralic, I. Wildfang, R. Bahrehmand, R. Engenhart-Cabilic and S.E. Schild, Short-course radiotherapy is not optimal for spinal cord compression due to myeloma. Int J Radiat Oncol Biol Phys,  64 5 (2006), pp. 1452–1457.

7 D. Rades, L.J. Stalpers, T. Veninga, V. Rudat, R. Schulte and P.J. Hoskin, Evaluation of functional outcome and local control after radiotherapy for metastatic spinal cord compression in patients with prostate cancer. J Urol,  175 2 (2006), pp. 552–556.

8 D. Rades, T. Veninga, L.J. Stalpers, R. Schulte, P.J. Hoskin, P. Poortmans, S.E. Schild and V. Rudat, Prognostic factors predicting functional outcomes, recurrence-free survival, and overall survival after radiotherapy for metastatic spinal cord compression in breast cancer patients. Int J Radiat Oncol Biol Phys,  64 1 (2006), pp. 182–188.

9 D. Rades, F. Fehlauer, L.J. Stalpers, I. Wildfang, O. Zschenker, S.E. Schild, H.J. Schmoll, J.H. Karstens and W. Alberti, A prospective evaluation of two radiotherapy schedules with 10 versus 20 fractions for the treatment of metastatic spinal cord compression: final results of a multicenter study. Cancer,  101 11 (2004), pp. 2687–2692.

10 D. Rades, T. Veninga, L.J. Stalpers, H. Basic, V. Rudat, J.H. Karstens, J. Dunst and S.E. Schild, Outcome after radiotherapy alone for metastatic spinal cord compression in patients with oligometastases. J Clin Oncol,  25 1 (2007), pp. 50–56.

Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Correspondence to: Ramachandran Venkitaraman, MD, MRCP, FRCR, Suffolk Oncology Centre, Ipswich Hospital NHS, Heath Road, Ipswich, IP4 5PD, UK; telephone: (0044) 1473704177; fax: (0044) 1473704916

Author Vitae
Dr. Venkitaraman is Consultant Clinical Oncologist, Suffolk Oncology Centre, Ipswich Hospital NHS, Ipswich, United Kingdom.

The Journal of Supportive Oncology

Review

Understanding Bereavement: What Every Oncology Practitioner Should Know

Elizabeth Kacel BA, Xin Gao BS, Holly G. Prigerson PhD 

[Author vitae]

Received 4 January 2011; Accepted 29 March 2011. Available online 24 September 2011.

Abstract

Death and dying are ever-present in the practice of oncology. Oncology clinic staff regularly encounter terminally ill patients and grieving family members and, therefore, are well positioned to identify and intervene on behalf of those at risk for extreme psychological distress. It is important for oncology providers to understand grief, the factors that heighten the risk for maladjustment to the loss, and how best to ease the emotional pain and suffering of bereaved family members. This article highlights models of grief that examine early relationships, relationships at the time of the loss, cognitive processes, and cultural practices. We also discuss special circumstances of grief such as the loss of a child or parent and grief in young adults. Risk factors for severe grief reactions, specifically prolonged grief disorder, are examined, as are the efficacy of various interventions, including staff support, psychodynamic therapy, cognitive-behavioral therapy, interpersonal therapy, group therapy, and Internet interventions. Overall, the literature on treatment for grief has demonstrated mixed results, but some therapies have shown promise in treating particularly distressed families and individuals. We discuss the clinical significance of grief and the importance of recognizing the unique factors which contribute to individuals' abilities to cope with loss.

*For a PDF of the full article and accompanying viewpoints by Noreen Carrington and Charles F. von Gunten and Judith Lacey, click on the links to the left of this introduction.

The Journal of Supportive Oncology

Review

Understanding Bereavement: What Every Oncology Practitioner Should Know

Elizabeth Kacel BA, Xin Gao BS, Holly G. Prigerson PhD 

[Author vitae]

Received 4 January 2011; Accepted 29 March 2011. Available online 24 September 2011.

Abstract

Death and dying are ever-present in the practice of oncology. Oncology clinic staff regularly encounter terminally ill patients and grieving family members and, therefore, are well positioned to identify and intervene on behalf of those at risk for extreme psychological distress. It is important for oncology providers to understand grief, the factors that heighten the risk for maladjustment to the loss, and how best to ease the emotional pain and suffering of bereaved family members. This article highlights models of grief that examine early relationships, relationships at the time of the loss, cognitive processes, and cultural practices. We also discuss special circumstances of grief such as the loss of a child or parent and grief in young adults. Risk factors for severe grief reactions, specifically prolonged grief disorder, are examined, as are the efficacy of various interventions, including staff support, psychodynamic therapy, cognitive-behavioral therapy, interpersonal therapy, group therapy, and Internet interventions. Overall, the literature on treatment for grief has demonstrated mixed results, but some therapies have shown promise in treating particularly distressed families and individuals. We discuss the clinical significance of grief and the importance of recognizing the unique factors which contribute to individuals' abilities to cope with loss.

*For a PDF of the full article and accompanying viewpoints by Noreen Carrington and Charles F. von Gunten and Judith Lacey, click on the links to the left of this introduction.

The Journal of Supportive Oncology

Review

Understanding Bereavement: What Every Oncology Practitioner Should Know

Elizabeth Kacel BA, Xin Gao BS, Holly G. Prigerson PhD 

[Author vitae]

Received 4 January 2011; Accepted 29 March 2011. Available online 24 September 2011.

Abstract

Death and dying are ever-present in the practice of oncology. Oncology clinic staff regularly encounter terminally ill patients and grieving family members and, therefore, are well positioned to identify and intervene on behalf of those at risk for extreme psychological distress. It is important for oncology providers to understand grief, the factors that heighten the risk for maladjustment to the loss, and how best to ease the emotional pain and suffering of bereaved family members. This article highlights models of grief that examine early relationships, relationships at the time of the loss, cognitive processes, and cultural practices. We also discuss special circumstances of grief such as the loss of a child or parent and grief in young adults. Risk factors for severe grief reactions, specifically prolonged grief disorder, are examined, as are the efficacy of various interventions, including staff support, psychodynamic therapy, cognitive-behavioral therapy, interpersonal therapy, group therapy, and Internet interventions. Overall, the literature on treatment for grief has demonstrated mixed results, but some therapies have shown promise in treating particularly distressed families and individuals. We discuss the clinical significance of grief and the importance of recognizing the unique factors which contribute to individuals' abilities to cope with loss.

*For a PDF of the full article and accompanying viewpoints by Noreen Carrington and Charles F. von Gunten and Judith Lacey, click on the links to the left of this introduction.

A common chemotherapy regimen gets reclassified as high risk for emesis; a new approach is recommended to tackle treatments with high emetic potential; and a particular antiemetic drug is now preferred for patients at moderate risk – these are among the changes to clinical practice guidelines from the American Society of Clinical Oncology.

The guidelines also include new recommendations for preventing nausea and vomiting associated with radiation treatment.

Treatment-related nausea and vomiting is reported by more than half of patients. If it is severe enough, dehydration and other adverse health effects can result and can limit treatment and patient outcomes.

One key change to the guidelines involves the chemotherapeutic agents anthracycline and cyclophosphamide, each of which carries a moderate risk for emesis if used alone. However, when the two are prescribed together, the patient’s risk for emesis is high. This upstaging to high risk is important, the authors wrote, because these agents are commonly combined, particularly to combat breast cancer and non-Hodgkin’s lymphoma.

For this and other high-risk therapies, the guidelines now recommend use of newer antiemetics. For example, a 5-hydroxytryptamine-3 (5-HT₃) receptor antagonist in combination with dexamethasone and a neurokinin 1 (NK₁) receptor antagonist is suggested to prevent significant nausea and vomiting.

In addition, a new NK1 receptor agonist, fosaprepitant (Emend, Merck), is available as a new, 1-day intravenous formulation of aprepitant, which needs to be infused over 3 days. The therapeutic equivalence of these two drugs was demonstrated in a large trial (J. Clin. Oncol. 2011;29:1495-501) and thus either one is appropriate, according to the guidelines. The briefer administration of fosaprepitant "may represent a more convenient or feasible option for some patients," the guideline update committee noted.

These and other revisions are based on new research findings since the last update to the guidelines in 2006. The 14-member committee reviewed 37 randomized, controlled trials, searched the Cochrane Collaboration Library, and evaluated presentations from the annual meetings of the American Society of Clinical Oncology and the Multinational Association of Supportive Care in Cancer.

The antiemetic recommendations are categorized according to the emesis risk of the chemotherapy regimens. For example, palonosetron (Aloxi, Helsinn Healthcare), is listed as preferential for moderate–emetic-risk regimens when given on day 1 and when combined with dexamethasone on days 1-3. If palonosetron is not available, the authors state that granisetron or ondansetron may be substituted.

In addition, a single, 8-mg dexamethasone dose alone is appropriate before the first dose of cancer-fighting agents associated with a low risk for emesis. And no antiemetic prophylaxis is necessary for chemotherapy regimens deemed to have minimal risk, according to the guidelines. These recommendations have remained the same since the last guideline update.

Recommendations regarding radiation treatment are likewise stratified by risk for emesis. For example, when a radiation course carries a high emetic risk, the guidelines recommend a 5-HT₃ agent prior to each fraction and for at least 24 hours following completion of radiotherapy. The update committee dropped the recommendation that this therapy be given with or without a corticosteroid and added that a 5-day course of dexamethasone is indicated during fractions one to five.

For moderate-risk radiation therapy, a 5-HT₃ antagonist before each fraction throughout radiotherapy remains the recommendation, with addition of a short course of dexamethasone during fractions one to five.

And for low-risk radiotherapy, the committee recommends a 5-HT₃ antagonist alone as either prophylaxis or rescue. This represents a change from the 2006 recommendation for administration of a 5-HT₃ agent before each fraction.

For minimal-risk radiotherapy, the new recommendation is for rescue therapy with either a dopamine receptor antagonist or a 5-HT₃ antagonist. This is similar to the 2006 recommendation for a dopamine or serotonin receptor antagonist on an as-needed basis.

When rescue antiemetic therapy is given, the authors recommend that prophylactic treatment be continued until radiotherapy is completed.

Other major themes of the guidelines include a need for continued symptom monitoring and a recognition that clinicians tend to underestimate the incidence of nausea; therefore, nausea is often less well controlled than emesis.

Some members of the update committee had the following financial disclosures: Dr. Paul Hesketh is a consultant to Eisai, GlaxoSmithKline, Helsinn, and Merck; Dr. Mark G. Kris is a consultant to Sanofi-Aventis and GlaxoSmithKline; and Dr. Petra C. Feyer is a consultant to GSK and Merck. Dr. Rebecca Clark-Snow receives honoraria from Merck, and Dr. Feyer receives honoraria from Merck, GSK, and Roche.

A common chemotherapy regimen gets reclassified as high risk for emesis; a new approach is recommended to tackle treatments with high emetic potential; and a particular antiemetic drug is now preferred for patients at moderate risk – these are among the changes to clinical practice guidelines from the American Society of Clinical Oncology.

The guidelines also include new recommendations for preventing nausea and vomiting associated with radiation treatment.

Treatment-related nausea and vomiting is reported by more than half of patients. If it is severe enough, dehydration and other adverse health effects can result and can limit treatment and patient outcomes.

One key change to the guidelines involves the chemotherapeutic agents anthracycline and cyclophosphamide, each of which carries a moderate risk for emesis if used alone. However, when the two are prescribed together, the patient’s risk for emesis is high. This upstaging to high risk is important, the authors wrote, because these agents are commonly combined, particularly to combat breast cancer and non-Hodgkin’s lymphoma.

For this and other high-risk therapies, the guidelines now recommend use of newer antiemetics. For example, a 5-hydroxytryptamine-3 (5-HT₃) receptor antagonist in combination with dexamethasone and a neurokinin 1 (NK₁) receptor antagonist is suggested to prevent significant nausea and vomiting.

In addition, a new NK1 receptor agonist, fosaprepitant (Emend, Merck), is available as a new, 1-day intravenous formulation of aprepitant, which needs to be infused over 3 days. The therapeutic equivalence of these two drugs was demonstrated in a large trial (J. Clin. Oncol. 2011;29:1495-501) and thus either one is appropriate, according to the guidelines. The briefer administration of fosaprepitant "may represent a more convenient or feasible option for some patients," the guideline update committee noted.

These and other revisions are based on new research findings since the last update to the guidelines in 2006. The 14-member committee reviewed 37 randomized, controlled trials, searched the Cochrane Collaboration Library, and evaluated presentations from the annual meetings of the American Society of Clinical Oncology and the Multinational Association of Supportive Care in Cancer.

The antiemetic recommendations are categorized according to the emesis risk of the chemotherapy regimens. For example, palonosetron (Aloxi, Helsinn Healthcare), is listed as preferential for moderate–emetic-risk regimens when given on day 1 and when combined with dexamethasone on days 1-3. If palonosetron is not available, the authors state that granisetron or ondansetron may be substituted.

In addition, a single, 8-mg dexamethasone dose alone is appropriate before the first dose of cancer-fighting agents associated with a low risk for emesis. And no antiemetic prophylaxis is necessary for chemotherapy regimens deemed to have minimal risk, according to the guidelines. These recommendations have remained the same since the last guideline update.

Recommendations regarding radiation treatment are likewise stratified by risk for emesis. For example, when a radiation course carries a high emetic risk, the guidelines recommend a 5-HT₃ agent prior to each fraction and for at least 24 hours following completion of radiotherapy. The update committee dropped the recommendation that this therapy be given with or without a corticosteroid and added that a 5-day course of dexamethasone is indicated during fractions one to five.

For moderate-risk radiation therapy, a 5-HT₃ antagonist before each fraction throughout radiotherapy remains the recommendation, with addition of a short course of dexamethasone during fractions one to five.

And for low-risk radiotherapy, the committee recommends a 5-HT₃ antagonist alone as either prophylaxis or rescue. This represents a change from the 2006 recommendation for administration of a 5-HT₃ agent before each fraction.

For minimal-risk radiotherapy, the new recommendation is for rescue therapy with either a dopamine receptor antagonist or a 5-HT₃ antagonist. This is similar to the 2006 recommendation for a dopamine or serotonin receptor antagonist on an as-needed basis.

When rescue antiemetic therapy is given, the authors recommend that prophylactic treatment be continued until radiotherapy is completed.

Other major themes of the guidelines include a need for continued symptom monitoring and a recognition that clinicians tend to underestimate the incidence of nausea; therefore, nausea is often less well controlled than emesis.

Some members of the update committee had the following financial disclosures: Dr. Paul Hesketh is a consultant to Eisai, GlaxoSmithKline, Helsinn, and Merck; Dr. Mark G. Kris is a consultant to Sanofi-Aventis and GlaxoSmithKline; and Dr. Petra C. Feyer is a consultant to GSK and Merck. Dr. Rebecca Clark-Snow receives honoraria from Merck, and Dr. Feyer receives honoraria from Merck, GSK, and Roche.

A common chemotherapy regimen gets reclassified as high risk for emesis; a new approach is recommended to tackle treatments with high emetic potential; and a particular antiemetic drug is now preferred for patients at moderate risk – these are among the changes to clinical practice guidelines from the American Society of Clinical Oncology.

The guidelines also include new recommendations for preventing nausea and vomiting associated with radiation treatment.

Treatment-related nausea and vomiting is reported by more than half of patients. If it is severe enough, dehydration and other adverse health effects can result and can limit treatment and patient outcomes.

One key change to the guidelines involves the chemotherapeutic agents anthracycline and cyclophosphamide, each of which carries a moderate risk for emesis if used alone. However, when the two are prescribed together, the patient’s risk for emesis is high. This upstaging to high risk is important, the authors wrote, because these agents are commonly combined, particularly to combat breast cancer and non-Hodgkin’s lymphoma.

For this and other high-risk therapies, the guidelines now recommend use of newer antiemetics. For example, a 5-hydroxytryptamine-3 (5-HT₃) receptor antagonist in combination with dexamethasone and a neurokinin 1 (NK₁) receptor antagonist is suggested to prevent significant nausea and vomiting.

In addition, a new NK1 receptor agonist, fosaprepitant (Emend, Merck), is available as a new, 1-day intravenous formulation of aprepitant, which needs to be infused over 3 days. The therapeutic equivalence of these two drugs was demonstrated in a large trial (J. Clin. Oncol. 2011;29:1495-501) and thus either one is appropriate, according to the guidelines. The briefer administration of fosaprepitant "may represent a more convenient or feasible option for some patients," the guideline update committee noted.

These and other revisions are based on new research findings since the last update to the guidelines in 2006. The 14-member committee reviewed 37 randomized, controlled trials, searched the Cochrane Collaboration Library, and evaluated presentations from the annual meetings of the American Society of Clinical Oncology and the Multinational Association of Supportive Care in Cancer.

The antiemetic recommendations are categorized according to the emesis risk of the chemotherapy regimens. For example, palonosetron (Aloxi, Helsinn Healthcare), is listed as preferential for moderate–emetic-risk regimens when given on day 1 and when combined with dexamethasone on days 1-3. If palonosetron is not available, the authors state that granisetron or ondansetron may be substituted.

In addition, a single, 8-mg dexamethasone dose alone is appropriate before the first dose of cancer-fighting agents associated with a low risk for emesis. And no antiemetic prophylaxis is necessary for chemotherapy regimens deemed to have minimal risk, according to the guidelines. These recommendations have remained the same since the last guideline update.

Recommendations regarding radiation treatment are likewise stratified by risk for emesis. For example, when a radiation course carries a high emetic risk, the guidelines recommend a 5-HT₃ agent prior to each fraction and for at least 24 hours following completion of radiotherapy. The update committee dropped the recommendation that this therapy be given with or without a corticosteroid and added that a 5-day course of dexamethasone is indicated during fractions one to five.

For moderate-risk radiation therapy, a 5-HT₃ antagonist before each fraction throughout radiotherapy remains the recommendation, with addition of a short course of dexamethasone during fractions one to five.

And for low-risk radiotherapy, the committee recommends a 5-HT₃ antagonist alone as either prophylaxis or rescue. This represents a change from the 2006 recommendation for administration of a 5-HT₃ agent before each fraction.

For minimal-risk radiotherapy, the new recommendation is for rescue therapy with either a dopamine receptor antagonist or a 5-HT₃ antagonist. This is similar to the 2006 recommendation for a dopamine or serotonin receptor antagonist on an as-needed basis.

When rescue antiemetic therapy is given, the authors recommend that prophylactic treatment be continued until radiotherapy is completed.

Other major themes of the guidelines include a need for continued symptom monitoring and a recognition that clinicians tend to underestimate the incidence of nausea; therefore, nausea is often less well controlled than emesis.

Some members of the update committee had the following financial disclosures: Dr. Paul Hesketh is a consultant to Eisai, GlaxoSmithKline, Helsinn, and Merck; Dr. Mark G. Kris is a consultant to Sanofi-Aventis and GlaxoSmithKline; and Dr. Petra C. Feyer is a consultant to GSK and Merck. Dr. Rebecca Clark-Snow receives honoraria from Merck, and Dr. Feyer receives honoraria from Merck, GSK, and Roche.

STOCKHOLM – Prostate cancer patients with bone metastases may find relief from bone pain in a single infusion of ibandronate instead of standard single-dose palliative radiotherapy.

"Overall, there is no difference in the probability of pain relief after single-dose radiotherapy or single-infusion ibandronate [Boniva], with overall response rates of around 52%," Dr. Peter Hoskin said at the European Multidisciplinary Cancer Congress.

He reported on the RIB (Single-Dose Local Radiation Therapy Compared With Ibandronate in Treating Patients With Localized Metastatic Bone Pain) trial involving 470 patients with prostate cancer or a raised prostate-specific antigen level of more than 100 ng/mL. Participants were evenly randomized to a single dose of 8 Gy local radiotherapy or a single 6-mg IV infusion of ibandronate. All patients were bisphosphonate free for at least 6 months, and roughly 90% were on androgen-deprivation therapy.

Patients provided details on analgesic use and rated their pain over the preceding 3 days using the Brief Pain Inventory (a categorical scale for worst pain, average pain, and least pain).

Pain response was measured using a combination of two different methods of analgesic score: a simple 3-point scale for analgesic strength based on the World Health Organization analgesic ladder, and an opioid equivalence calculated to give a single continuous variable based on the method described by Dr. Sebastiano Mercadante and colleagues.

The overall pain response rate was 51.3% at 4 weeks and 52.7% at 12 weeks, said Dr. Hoskin, a professor of clinical oncology at University College London and a radiation oncologist at Mount Vernon Cancer Centre in Northwood, England. There was no evidence of a treatment effect for change in pain relief from baseline at either 4 or 12 weeks when either pain criterion was used.

The mean change in the WHO response rate at 4 weeks was –3.7% and 6.7% at 12 weeks. The mean change in the Mercadante score was 4.4 units at 4 weeks and –1.5 units at 12 weeks. None of these differences was statistically significant.

At 4 weeks, more patients in the ibandronate group had worse Mercadante scores. This is consistent with more patients’ needing retreatment at 4 weeks after ibandronate; however, by 8 weeks, there was no overall advantage, Dr. Hoskin said. In all, 31% of patients receiving ibandronate and 24% of those receiving radiotherapy crossed over to the opposite treatment (P = .097).

Overall toxicity was the same in both treatment groups, with any toxicity reported in 38% of the ibandronate group and 40% of the radiotherapy group. As expected, the radiotherapy group experienced more diarrhea and nausea, whereas the ibandronate group experienced infusion-related events.

At a median follow-up of 11.6 months, overall median survival was identical at 12.2 months with radiotherapy and 12.8 months with ibandronate, Dr. Hoskin said at the joint congress of the European Cancer Organization (ECCO), the European Society for Medical Oncology (ESMO), and the European Society of Radiotherapy and Oncology (ESTRO).

An analysis of crossover patients revealed a significant improvement in survival in the group receiving ibandronate who crossed over to radiotherapy at 4 weeks. Median survival in this group was 16.8 months, compared with 12.7 months in the group crossing over from radiotherapy to ibandronate.

"Perhaps ultimately, as these studies progress and new studies are undertaken, combined treatment with radiotherapy and bisphosphonate may be optimal and show synergistic action," he said.

Invited discussant Dr. Daniel Zips of the National Center for Radiation Research in Oncology in Dresden, Germany, said that radiotherapy will remain the standard of care for most patients with localized bone pain resulting from metastases, but that ibandronate represents an effective treatment option for special clinical situations such as patients with contraindications to radiotherapy.

"The results of the crossover – and this might even be more important – suggest that radiotherapy or ibandronate represents a treatment option for patients who fail the first treatment," he added.

Given that only 50% overall responded to ibandronate or radiotherapy, Dr. Zips said that better, more effective therapies are clearly needed to improve the treatment of bone metastases.

RIB was sponsored by the Cancer Research UK and UCL Cancer Trials Centre. Dr. Hoskin disclosed no relevant conflicts of interest.

STOCKHOLM – Prostate cancer patients with bone metastases may find relief from bone pain in a single infusion of ibandronate instead of standard single-dose palliative radiotherapy.

"Overall, there is no difference in the probability of pain relief after single-dose radiotherapy or single-infusion ibandronate [Boniva], with overall response rates of around 52%," Dr. Peter Hoskin said at the European Multidisciplinary Cancer Congress.

He reported on the RIB (Single-Dose Local Radiation Therapy Compared With Ibandronate in Treating Patients With Localized Metastatic Bone Pain) trial involving 470 patients with prostate cancer or a raised prostate-specific antigen level of more than 100 ng/mL. Participants were evenly randomized to a single dose of 8 Gy local radiotherapy or a single 6-mg IV infusion of ibandronate. All patients were bisphosphonate free for at least 6 months, and roughly 90% were on androgen-deprivation therapy.

Patients provided details on analgesic use and rated their pain over the preceding 3 days using the Brief Pain Inventory (a categorical scale for worst pain, average pain, and least pain).

Pain response was measured using a combination of two different methods of analgesic score: a simple 3-point scale for analgesic strength based on the World Health Organization analgesic ladder, and an opioid equivalence calculated to give a single continuous variable based on the method described by Dr. Sebastiano Mercadante and colleagues.

The overall pain response rate was 51.3% at 4 weeks and 52.7% at 12 weeks, said Dr. Hoskin, a professor of clinical oncology at University College London and a radiation oncologist at Mount Vernon Cancer Centre in Northwood, England. There was no evidence of a treatment effect for change in pain relief from baseline at either 4 or 12 weeks when either pain criterion was used.

The mean change in the WHO response rate at 4 weeks was –3.7% and 6.7% at 12 weeks. The mean change in the Mercadante score was 4.4 units at 4 weeks and –1.5 units at 12 weeks. None of these differences was statistically significant.

At 4 weeks, more patients in the ibandronate group had worse Mercadante scores. This is consistent with more patients’ needing retreatment at 4 weeks after ibandronate; however, by 8 weeks, there was no overall advantage, Dr. Hoskin said. In all, 31% of patients receiving ibandronate and 24% of those receiving radiotherapy crossed over to the opposite treatment (P = .097).

Overall toxicity was the same in both treatment groups, with any toxicity reported in 38% of the ibandronate group and 40% of the radiotherapy group. As expected, the radiotherapy group experienced more diarrhea and nausea, whereas the ibandronate group experienced infusion-related events.

At a median follow-up of 11.6 months, overall median survival was identical at 12.2 months with radiotherapy and 12.8 months with ibandronate, Dr. Hoskin said at the joint congress of the European Cancer Organization (ECCO), the European Society for Medical Oncology (ESMO), and the European Society of Radiotherapy and Oncology (ESTRO).

An analysis of crossover patients revealed a significant improvement in survival in the group receiving ibandronate who crossed over to radiotherapy at 4 weeks. Median survival in this group was 16.8 months, compared with 12.7 months in the group crossing over from radiotherapy to ibandronate.

"Perhaps ultimately, as these studies progress and new studies are undertaken, combined treatment with radiotherapy and bisphosphonate may be optimal and show synergistic action," he said.

Invited discussant Dr. Daniel Zips of the National Center for Radiation Research in Oncology in Dresden, Germany, said that radiotherapy will remain the standard of care for most patients with localized bone pain resulting from metastases, but that ibandronate represents an effective treatment option for special clinical situations such as patients with contraindications to radiotherapy.

"The results of the crossover – and this might even be more important – suggest that radiotherapy or ibandronate represents a treatment option for patients who fail the first treatment," he added.

Given that only 50% overall responded to ibandronate or radiotherapy, Dr. Zips said that better, more effective therapies are clearly needed to improve the treatment of bone metastases.

RIB was sponsored by the Cancer Research UK and UCL Cancer Trials Centre. Dr. Hoskin disclosed no relevant conflicts of interest.

STOCKHOLM – Prostate cancer patients with bone metastases may find relief from bone pain in a single infusion of ibandronate instead of standard single-dose palliative radiotherapy.

"Overall, there is no difference in the probability of pain relief after single-dose radiotherapy or single-infusion ibandronate [Boniva], with overall response rates of around 52%," Dr. Peter Hoskin said at the European Multidisciplinary Cancer Congress.

He reported on the RIB (Single-Dose Local Radiation Therapy Compared With Ibandronate in Treating Patients With Localized Metastatic Bone Pain) trial involving 470 patients with prostate cancer or a raised prostate-specific antigen level of more than 100 ng/mL. Participants were evenly randomized to a single dose of 8 Gy local radiotherapy or a single 6-mg IV infusion of ibandronate. All patients were bisphosphonate free for at least 6 months, and roughly 90% were on androgen-deprivation therapy.

Patients provided details on analgesic use and rated their pain over the preceding 3 days using the Brief Pain Inventory (a categorical scale for worst pain, average pain, and least pain).

Pain response was measured using a combination of two different methods of analgesic score: a simple 3-point scale for analgesic strength based on the World Health Organization analgesic ladder, and an opioid equivalence calculated to give a single continuous variable based on the method described by Dr. Sebastiano Mercadante and colleagues.

The overall pain response rate was 51.3% at 4 weeks and 52.7% at 12 weeks, said Dr. Hoskin, a professor of clinical oncology at University College London and a radiation oncologist at Mount Vernon Cancer Centre in Northwood, England. There was no evidence of a treatment effect for change in pain relief from baseline at either 4 or 12 weeks when either pain criterion was used.

The mean change in the WHO response rate at 4 weeks was –3.7% and 6.7% at 12 weeks. The mean change in the Mercadante score was 4.4 units at 4 weeks and –1.5 units at 12 weeks. None of these differences was statistically significant.

At 4 weeks, more patients in the ibandronate group had worse Mercadante scores. This is consistent with more patients’ needing retreatment at 4 weeks after ibandronate; however, by 8 weeks, there was no overall advantage, Dr. Hoskin said. In all, 31% of patients receiving ibandronate and 24% of those receiving radiotherapy crossed over to the opposite treatment (P = .097).

Overall toxicity was the same in both treatment groups, with any toxicity reported in 38% of the ibandronate group and 40% of the radiotherapy group. As expected, the radiotherapy group experienced more diarrhea and nausea, whereas the ibandronate group experienced infusion-related events.

At a median follow-up of 11.6 months, overall median survival was identical at 12.2 months with radiotherapy and 12.8 months with ibandronate, Dr. Hoskin said at the joint congress of the European Cancer Organization (ECCO), the European Society for Medical Oncology (ESMO), and the European Society of Radiotherapy and Oncology (ESTRO).

An analysis of crossover patients revealed a significant improvement in survival in the group receiving ibandronate who crossed over to radiotherapy at 4 weeks. Median survival in this group was 16.8 months, compared with 12.7 months in the group crossing over from radiotherapy to ibandronate.

"Perhaps ultimately, as these studies progress and new studies are undertaken, combined treatment with radiotherapy and bisphosphonate may be optimal and show synergistic action," he said.

Invited discussant Dr. Daniel Zips of the National Center for Radiation Research in Oncology in Dresden, Germany, said that radiotherapy will remain the standard of care for most patients with localized bone pain resulting from metastases, but that ibandronate represents an effective treatment option for special clinical situations such as patients with contraindications to radiotherapy.

"The results of the crossover – and this might even be more important – suggest that radiotherapy or ibandronate represents a treatment option for patients who fail the first treatment," he added.

Given that only 50% overall responded to ibandronate or radiotherapy, Dr. Zips said that better, more effective therapies are clearly needed to improve the treatment of bone metastases.

RIB was sponsored by the Cancer Research UK and UCL Cancer Trials Centre. Dr. Hoskin disclosed no relevant conflicts of interest.