Patient & Survivor Care

SAN FRANCISCO – The development of taxane-induced peripheral neuropathy does not appear to be a marker for better outcomes in women with early breast cancer, new data show.

In a secondary analysis of the Eastern Cooperative Oncology Group E1199 trial involving 4,554 women, 13%-22% developed peripheral neuropathy, depending on which of four taxane regimens they received.

The women who developed peripheral neuropathy did not have better recurrence-free, disease-free, or overall survival than did their counterparts who escaped this toxicity, lead investigator Dr. Bryan P. Schneider reported on behalf of several North American breast cancer groups. Results were the same regardless of tumor type (estrogen receptor positive, HER2 positive, or triple negative) and the taxane regimen received.

He noted that the findings are important, given recent identification of six single-nucleotide polymorphisms (SNPs) predicting the likelihood of peripheral neuropathy in women receiving paclitaxel-containing chemotherapy (ASCO 2011, abstract 1000).

"Neuropathy did not correlate with outcome in E1199. The relevance is that SNPs or biomarkers that predict a subgroup protected from neuropathy are thus unlikely to enrich for inferior outcome," he explained.

Discussant Dr. William J. Gradishar, director of the center for women’s cancer care at Northwestern University in Chicago, said that "at the end of the day, at least with the present data we have, it doesn’t appear that the presence of neuropathy has any bearing on overall clinical outcome from those end points."

Trials thus far have failed to identify effective agents for preventing peripheral neuropathy in this setting, but there are some new agents on the horizon, he noted.

"The hope will be, because these [chemotherapy drugs] are such a mainstay of our therapies in both the adjuvant and metastatic disease setting, that one or a few of [the new agents] may ultimately prove to be fruitful for our patients," concluded Dr. Gradishar.

Women participating in the E1199 trial all received four cycles of doxorubicin and cyclophosphamide. They then received one of four taxane regimens: paclitaxel (Taxol) every 3 weeks for 4 cycles (control), paclitaxel weekly for 12 cycles, docetaxel (Taxotere) every 3 weeks for 4 cycles, or docetaxel weekly for 12 cycles. Median follow-up was 95.5 months.

Peripheral neuropathy (grade 2-4, either sensory or motor) was the most common nonhematologic toxicity seen in the trial, according to Dr. Schneider of Indiana University in Indianapolis. It occurred in 22.0% of women treated with weekly paclitaxel, in 17.5% of women treated with paclitaxel every 3 weeks, in 14.7% of women treated with docetaxel every 3 weeks, and in 13.4% of women treated with weekly docetaxel.

In a multivariate model, women were significantly more likely to develop peripheral neuropathy if they had treatment-associated hyperglycemia (hazard ratio, 1.47), and were marginally more likely if they were black, obese, or postmenopausal.

Risk also varied by taxane regimen. It was higher for women who received weekly paclitaxel vs. paclitaxel every 3 week (HR, 1.52), paclitaxel every 3 weeks vs. weekly docetaxel (HR, 3.00), or paclitaxel every 3 weeks vs. docetaxel every 3 weeks (HR, 1.91).

In several types of analyses including multivariate models, the development of peripheral neuropathy was not significantly associated with recurrence-free, disease-free, or overall survival.

The findings contrast with those of an earlier study in which women receiving paclitaxel-containing chemotherapy without trastuzumab did have better outcomes if they developed peripheral neuropathy (SABCS 2009, abstract A-2100).

"Every-3-week docetaxel and weekly paclitaxel are viable therapeutic options for breast cancer," commented Dr. Schneider. The former is associated with more grade 3/4 toxicity in general, whereas the latter is associated with more peripheral neuropathy.

"Our goal is to study SNPs that have previously been shown to predict neuropathy in E1199," he concluded. "We hope to validate those top SNPs and ultimately identify which therapy has the optimal risk-benefit ratio for a given subgroup based on genotype."

Dr. Schneider reported that he had no relevant conflicts of interest. Dr. Gradishar had relationships with several companies that make taxanes.

SAN FRANCISCO – The development of taxane-induced peripheral neuropathy does not appear to be a marker for better outcomes in women with early breast cancer, new data show.

In a secondary analysis of the Eastern Cooperative Oncology Group E1199 trial involving 4,554 women, 13%-22% developed peripheral neuropathy, depending on which of four taxane regimens they received.

The women who developed peripheral neuropathy did not have better recurrence-free, disease-free, or overall survival than did their counterparts who escaped this toxicity, lead investigator Dr. Bryan P. Schneider reported on behalf of several North American breast cancer groups. Results were the same regardless of tumor type (estrogen receptor positive, HER2 positive, or triple negative) and the taxane regimen received.

He noted that the findings are important, given recent identification of six single-nucleotide polymorphisms (SNPs) predicting the likelihood of peripheral neuropathy in women receiving paclitaxel-containing chemotherapy (ASCO 2011, abstract 1000).

"Neuropathy did not correlate with outcome in E1199. The relevance is that SNPs or biomarkers that predict a subgroup protected from neuropathy are thus unlikely to enrich for inferior outcome," he explained.

Discussant Dr. William J. Gradishar, director of the center for women’s cancer care at Northwestern University in Chicago, said that "at the end of the day, at least with the present data we have, it doesn’t appear that the presence of neuropathy has any bearing on overall clinical outcome from those end points."

Trials thus far have failed to identify effective agents for preventing peripheral neuropathy in this setting, but there are some new agents on the horizon, he noted.

"The hope will be, because these [chemotherapy drugs] are such a mainstay of our therapies in both the adjuvant and metastatic disease setting, that one or a few of [the new agents] may ultimately prove to be fruitful for our patients," concluded Dr. Gradishar.

Women participating in the E1199 trial all received four cycles of doxorubicin and cyclophosphamide. They then received one of four taxane regimens: paclitaxel (Taxol) every 3 weeks for 4 cycles (control), paclitaxel weekly for 12 cycles, docetaxel (Taxotere) every 3 weeks for 4 cycles, or docetaxel weekly for 12 cycles. Median follow-up was 95.5 months.

Peripheral neuropathy (grade 2-4, either sensory or motor) was the most common nonhematologic toxicity seen in the trial, according to Dr. Schneider of Indiana University in Indianapolis. It occurred in 22.0% of women treated with weekly paclitaxel, in 17.5% of women treated with paclitaxel every 3 weeks, in 14.7% of women treated with docetaxel every 3 weeks, and in 13.4% of women treated with weekly docetaxel.

In a multivariate model, women were significantly more likely to develop peripheral neuropathy if they had treatment-associated hyperglycemia (hazard ratio, 1.47), and were marginally more likely if they were black, obese, or postmenopausal.

Risk also varied by taxane regimen. It was higher for women who received weekly paclitaxel vs. paclitaxel every 3 week (HR, 1.52), paclitaxel every 3 weeks vs. weekly docetaxel (HR, 3.00), or paclitaxel every 3 weeks vs. docetaxel every 3 weeks (HR, 1.91).

In several types of analyses including multivariate models, the development of peripheral neuropathy was not significantly associated with recurrence-free, disease-free, or overall survival.

The findings contrast with those of an earlier study in which women receiving paclitaxel-containing chemotherapy without trastuzumab did have better outcomes if they developed peripheral neuropathy (SABCS 2009, abstract A-2100).

"Every-3-week docetaxel and weekly paclitaxel are viable therapeutic options for breast cancer," commented Dr. Schneider. The former is associated with more grade 3/4 toxicity in general, whereas the latter is associated with more peripheral neuropathy.

"Our goal is to study SNPs that have previously been shown to predict neuropathy in E1199," he concluded. "We hope to validate those top SNPs and ultimately identify which therapy has the optimal risk-benefit ratio for a given subgroup based on genotype."

Dr. Schneider reported that he had no relevant conflicts of interest. Dr. Gradishar had relationships with several companies that make taxanes.

SAN FRANCISCO – The development of taxane-induced peripheral neuropathy does not appear to be a marker for better outcomes in women with early breast cancer, new data show.

In a secondary analysis of the Eastern Cooperative Oncology Group E1199 trial involving 4,554 women, 13%-22% developed peripheral neuropathy, depending on which of four taxane regimens they received.

The women who developed peripheral neuropathy did not have better recurrence-free, disease-free, or overall survival than did their counterparts who escaped this toxicity, lead investigator Dr. Bryan P. Schneider reported on behalf of several North American breast cancer groups. Results were the same regardless of tumor type (estrogen receptor positive, HER2 positive, or triple negative) and the taxane regimen received.

He noted that the findings are important, given recent identification of six single-nucleotide polymorphisms (SNPs) predicting the likelihood of peripheral neuropathy in women receiving paclitaxel-containing chemotherapy (ASCO 2011, abstract 1000).

"Neuropathy did not correlate with outcome in E1199. The relevance is that SNPs or biomarkers that predict a subgroup protected from neuropathy are thus unlikely to enrich for inferior outcome," he explained.

Discussant Dr. William J. Gradishar, director of the center for women’s cancer care at Northwestern University in Chicago, said that "at the end of the day, at least with the present data we have, it doesn’t appear that the presence of neuropathy has any bearing on overall clinical outcome from those end points."

Trials thus far have failed to identify effective agents for preventing peripheral neuropathy in this setting, but there are some new agents on the horizon, he noted.

"The hope will be, because these [chemotherapy drugs] are such a mainstay of our therapies in both the adjuvant and metastatic disease setting, that one or a few of [the new agents] may ultimately prove to be fruitful for our patients," concluded Dr. Gradishar.

Women participating in the E1199 trial all received four cycles of doxorubicin and cyclophosphamide. They then received one of four taxane regimens: paclitaxel (Taxol) every 3 weeks for 4 cycles (control), paclitaxel weekly for 12 cycles, docetaxel (Taxotere) every 3 weeks for 4 cycles, or docetaxel weekly for 12 cycles. Median follow-up was 95.5 months.

Peripheral neuropathy (grade 2-4, either sensory or motor) was the most common nonhematologic toxicity seen in the trial, according to Dr. Schneider of Indiana University in Indianapolis. It occurred in 22.0% of women treated with weekly paclitaxel, in 17.5% of women treated with paclitaxel every 3 weeks, in 14.7% of women treated with docetaxel every 3 weeks, and in 13.4% of women treated with weekly docetaxel.

In a multivariate model, women were significantly more likely to develop peripheral neuropathy if they had treatment-associated hyperglycemia (hazard ratio, 1.47), and were marginally more likely if they were black, obese, or postmenopausal.

Risk also varied by taxane regimen. It was higher for women who received weekly paclitaxel vs. paclitaxel every 3 week (HR, 1.52), paclitaxel every 3 weeks vs. weekly docetaxel (HR, 3.00), or paclitaxel every 3 weeks vs. docetaxel every 3 weeks (HR, 1.91).

In several types of analyses including multivariate models, the development of peripheral neuropathy was not significantly associated with recurrence-free, disease-free, or overall survival.

The findings contrast with those of an earlier study in which women receiving paclitaxel-containing chemotherapy without trastuzumab did have better outcomes if they developed peripheral neuropathy (SABCS 2009, abstract A-2100).

"Every-3-week docetaxel and weekly paclitaxel are viable therapeutic options for breast cancer," commented Dr. Schneider. The former is associated with more grade 3/4 toxicity in general, whereas the latter is associated with more peripheral neuropathy.

"Our goal is to study SNPs that have previously been shown to predict neuropathy in E1199," he concluded. "We hope to validate those top SNPs and ultimately identify which therapy has the optimal risk-benefit ratio for a given subgroup based on genotype."

Dr. Schneider reported that he had no relevant conflicts of interest. Dr. Gradishar had relationships with several companies that make taxanes.

Depression emerged as a significant barrier to secondary cancer screening in Latina survivors of breast cancer in a thought-provoking study released Sept. 19 at the American Association of Cancer Research Conference on the Science of Cancer Health Disparities in Washington.

The cross-sectional study explored adherence to recommended screening guidelines for ovarian and colorectal cancer among 117 Latina breast cancer survivors. Not surprisingly, but disturbingly, adherence was low among this very-high-risk group. Nearly 60% (69 of 117) failed to receive standard screening for either disease.

One would hope that these high-risk women knew, based on their prior treatment, how to negotiate financial and logistical barriers to care. It would seem likely that they formed relationships with health care professionals. Certainly, it would be expected that they learned that early detection saves lives; perhaps, it had already saved theirs.

So what happened? How did the prevention message fail to reach women who had already directly faced the reality of a cancer diagnosis, and survived?

One sobering possibility lies in the fact that nearly a third of Latinas in the study met the criteria for depression, according to scores for the simple but comprehensive CES-D (Center for Epidemiologic Studies) screening tool.

The self-administered questionnaire assesses mood "("I felt that I could not shake off the blues, even with help from family or friends"; "I [did not] feel hopeful about the future"), somatic symptoms ("I did not feel like eating; my appetite was poor"), behavior ("I talked less than usual"), and self-concept ("I thought my life had been a failure").

Depression was associated with poor rates of ovarian screening, along with language barriers, unemployment, worries about the cost of screening, and the lack of a family history of cancer.

Poor rates of colorectal cancer screening were associated with being unmarried.

In online video interview from a 2010 AACR breast cancer meeting, the current study’s primary investigator, Amelie G. Ramirez, Dr. P.H., spoke of challenging issues surrounding Latina access to cancer prevention and care, driven by cultural as well as socioeconomic issues.

Sheer terror of cancer, she explained, wields a powerful influence over portions of the Latina community.

"When they hear the word cancer, it’s very fearful for them. It almost shuts down all ... communication," said Dr. Ramirez, director of the Institute for Health Promotion Research and professor of epidemiology and biostatistics at the University of Texas, San Antonio.

Depression, too, casts a dark, silent cloud over the Latino community.

In a 2009 study, University of California, Los Angeles, researchers identified a strong link between self-perceived stigma and secrecy surrounding depressive symptoms, less likelihood of taking antidepressants, and – importantly with regard to the current screening study – more missed medical appointments among Latinos.

Taken together, these studies and observations begin to paint a picture of the type of woman whose life might be reflected in the numbers in Dr. Ramirez’s study. She is poor and unemployed; she struggles with English. She survived a disease that is unspeakably terrifying in her community and perhaps in her family as well. She may be unmarried.

And now, with bills and scars still reminding her of the trauma, a new, equally unmentionable burden shadows her days. She sleeps restlessly and cannot eat; she is quiet and withdrawn; she cannot shake off the blues. She feels that her life has been a failure.

Assuming the best possible scenario, a card arrives in the mail, reminding her that she is due for cancer screening: an annual pelvic exam, perhaps, or a colonoscopy.

Is it any wonder she fails to comply?

Dr. Freed is a clinical psychologist in Santa Barbara, Calif., and a medical journalist. She has no relevant financial disclosures.

Depression emerged as a significant barrier to secondary cancer screening in Latina survivors of breast cancer in a thought-provoking study released Sept. 19 at the American Association of Cancer Research Conference on the Science of Cancer Health Disparities in Washington.

The cross-sectional study explored adherence to recommended screening guidelines for ovarian and colorectal cancer among 117 Latina breast cancer survivors. Not surprisingly, but disturbingly, adherence was low among this very-high-risk group. Nearly 60% (69 of 117) failed to receive standard screening for either disease.

One would hope that these high-risk women knew, based on their prior treatment, how to negotiate financial and logistical barriers to care. It would seem likely that they formed relationships with health care professionals. Certainly, it would be expected that they learned that early detection saves lives; perhaps, it had already saved theirs.

So what happened? How did the prevention message fail to reach women who had already directly faced the reality of a cancer diagnosis, and survived?

One sobering possibility lies in the fact that nearly a third of Latinas in the study met the criteria for depression, according to scores for the simple but comprehensive CES-D (Center for Epidemiologic Studies) screening tool.

The self-administered questionnaire assesses mood "("I felt that I could not shake off the blues, even with help from family or friends"; "I [did not] feel hopeful about the future"), somatic symptoms ("I did not feel like eating; my appetite was poor"), behavior ("I talked less than usual"), and self-concept ("I thought my life had been a failure").

Depression was associated with poor rates of ovarian screening, along with language barriers, unemployment, worries about the cost of screening, and the lack of a family history of cancer.

Poor rates of colorectal cancer screening were associated with being unmarried.

In online video interview from a 2010 AACR breast cancer meeting, the current study’s primary investigator, Amelie G. Ramirez, Dr. P.H., spoke of challenging issues surrounding Latina access to cancer prevention and care, driven by cultural as well as socioeconomic issues.

Sheer terror of cancer, she explained, wields a powerful influence over portions of the Latina community.

"When they hear the word cancer, it’s very fearful for them. It almost shuts down all ... communication," said Dr. Ramirez, director of the Institute for Health Promotion Research and professor of epidemiology and biostatistics at the University of Texas, San Antonio.

Depression, too, casts a dark, silent cloud over the Latino community.

In a 2009 study, University of California, Los Angeles, researchers identified a strong link between self-perceived stigma and secrecy surrounding depressive symptoms, less likelihood of taking antidepressants, and – importantly with regard to the current screening study – more missed medical appointments among Latinos.

Taken together, these studies and observations begin to paint a picture of the type of woman whose life might be reflected in the numbers in Dr. Ramirez’s study. She is poor and unemployed; she struggles with English. She survived a disease that is unspeakably terrifying in her community and perhaps in her family as well. She may be unmarried.

And now, with bills and scars still reminding her of the trauma, a new, equally unmentionable burden shadows her days. She sleeps restlessly and cannot eat; she is quiet and withdrawn; she cannot shake off the blues. She feels that her life has been a failure.

Assuming the best possible scenario, a card arrives in the mail, reminding her that she is due for cancer screening: an annual pelvic exam, perhaps, or a colonoscopy.

Is it any wonder she fails to comply?

Dr. Freed is a clinical psychologist in Santa Barbara, Calif., and a medical journalist. She has no relevant financial disclosures.

Depression emerged as a significant barrier to secondary cancer screening in Latina survivors of breast cancer in a thought-provoking study released Sept. 19 at the American Association of Cancer Research Conference on the Science of Cancer Health Disparities in Washington.

The cross-sectional study explored adherence to recommended screening guidelines for ovarian and colorectal cancer among 117 Latina breast cancer survivors. Not surprisingly, but disturbingly, adherence was low among this very-high-risk group. Nearly 60% (69 of 117) failed to receive standard screening for either disease.

One would hope that these high-risk women knew, based on their prior treatment, how to negotiate financial and logistical barriers to care. It would seem likely that they formed relationships with health care professionals. Certainly, it would be expected that they learned that early detection saves lives; perhaps, it had already saved theirs.

So what happened? How did the prevention message fail to reach women who had already directly faced the reality of a cancer diagnosis, and survived?

One sobering possibility lies in the fact that nearly a third of Latinas in the study met the criteria for depression, according to scores for the simple but comprehensive CES-D (Center for Epidemiologic Studies) screening tool.

The self-administered questionnaire assesses mood "("I felt that I could not shake off the blues, even with help from family or friends"; "I [did not] feel hopeful about the future"), somatic symptoms ("I did not feel like eating; my appetite was poor"), behavior ("I talked less than usual"), and self-concept ("I thought my life had been a failure").

Depression was associated with poor rates of ovarian screening, along with language barriers, unemployment, worries about the cost of screening, and the lack of a family history of cancer.

Poor rates of colorectal cancer screening were associated with being unmarried.

In online video interview from a 2010 AACR breast cancer meeting, the current study’s primary investigator, Amelie G. Ramirez, Dr. P.H., spoke of challenging issues surrounding Latina access to cancer prevention and care, driven by cultural as well as socioeconomic issues.

Sheer terror of cancer, she explained, wields a powerful influence over portions of the Latina community.

"When they hear the word cancer, it’s very fearful for them. It almost shuts down all ... communication," said Dr. Ramirez, director of the Institute for Health Promotion Research and professor of epidemiology and biostatistics at the University of Texas, San Antonio.

Depression, too, casts a dark, silent cloud over the Latino community.

In a 2009 study, University of California, Los Angeles, researchers identified a strong link between self-perceived stigma and secrecy surrounding depressive symptoms, less likelihood of taking antidepressants, and – importantly with regard to the current screening study – more missed medical appointments among Latinos.

Taken together, these studies and observations begin to paint a picture of the type of woman whose life might be reflected in the numbers in Dr. Ramirez’s study. She is poor and unemployed; she struggles with English. She survived a disease that is unspeakably terrifying in her community and perhaps in her family as well. She may be unmarried.

And now, with bills and scars still reminding her of the trauma, a new, equally unmentionable burden shadows her days. She sleeps restlessly and cannot eat; she is quiet and withdrawn; she cannot shake off the blues. She feels that her life has been a failure.

Assuming the best possible scenario, a card arrives in the mail, reminding her that she is due for cancer screening: an annual pelvic exam, perhaps, or a colonoscopy.

Is it any wonder she fails to comply?

Dr. Freed is a clinical psychologist in Santa Barbara, Calif., and a medical journalist. She has no relevant financial disclosures.

The Prolia brand of denosumab has been approved as a treatment for bone loss in people receiving hormone ablation therapy for prostate or breast cancer, according to a statement from Amgen, the manufacturer.

The approved indications are for increasing bone mass in women at high risk for fracture on adjuvant aromatase inhibitor therapy for breast cancer and in men at high risk for fracture on androgen deprivation therapy (ADT) for nonmetastatic prostate cancer, the company's statement said.

Denosumab, a RANK ligand inhibitor, was first approved in June 2010 for treating postmenopausal women with osteoporosis at high risk of fracture and is marketed as Prolia for this indication. Prolia is administered in a subcutaneous injection once every 6 months, at a dose of 60 mg.

In November 2010, denosumab was also approved for preventing skeletal-related events in patients with bone metastases from solid tumors. It is marketed as Xgeva and administered more frequently at a higher dose for this indication.

Approval of the new indications for Prolia was based on phase III studies of these two groups of patients, according to Amgen. In an international study of almost 1,500 men with nonmetastatic prostate cancer who were being treated with ADT, bone mineral density at the lumbar spine after 2 years of treatment was significantly higher among men who had received denosumab compared with those who received placebo. After 3 years of treatment, the incidence of new vertebral fractures was 1.5% among those treated with denosumab, compared with 3.9% for those on placebo, a risk reduction of 62%, the company said.

And in a study of 252 postmenopausal women with breast cancer under treatment with an aromatase inhibitor, bone mineral density at the lumbar spine was significantly higher among those treated with denosumab compared with those on placebo after 12 months of treatment, according to the statement.

Arthralgia and back pain were the most common adverse events associated with treatment in these two groups of patients. Hypocalcemia was also reported; denosumab is contraindicated in people with hypocalcemia. Treatment was associated with cataract events in men in the prostate cancer trial.

In the European Union, denosumab is approved for the osteoporosis indication as well as the prostate cancer indication just approved in the United States, according to Amgen.

The Prolia brand of denosumab has been approved as a treatment for bone loss in people receiving hormone ablation therapy for prostate or breast cancer, according to a statement from Amgen, the manufacturer.

The approved indications are for increasing bone mass in women at high risk for fracture on adjuvant aromatase inhibitor therapy for breast cancer and in men at high risk for fracture on androgen deprivation therapy (ADT) for nonmetastatic prostate cancer, the company's statement said.

Denosumab, a RANK ligand inhibitor, was first approved in June 2010 for treating postmenopausal women with osteoporosis at high risk of fracture and is marketed as Prolia for this indication. Prolia is administered in a subcutaneous injection once every 6 months, at a dose of 60 mg.

In November 2010, denosumab was also approved for preventing skeletal-related events in patients with bone metastases from solid tumors. It is marketed as Xgeva and administered more frequently at a higher dose for this indication.

Approval of the new indications for Prolia was based on phase III studies of these two groups of patients, according to Amgen. In an international study of almost 1,500 men with nonmetastatic prostate cancer who were being treated with ADT, bone mineral density at the lumbar spine after 2 years of treatment was significantly higher among men who had received denosumab compared with those who received placebo. After 3 years of treatment, the incidence of new vertebral fractures was 1.5% among those treated with denosumab, compared with 3.9% for those on placebo, a risk reduction of 62%, the company said.

And in a study of 252 postmenopausal women with breast cancer under treatment with an aromatase inhibitor, bone mineral density at the lumbar spine was significantly higher among those treated with denosumab compared with those on placebo after 12 months of treatment, according to the statement.

Arthralgia and back pain were the most common adverse events associated with treatment in these two groups of patients. Hypocalcemia was also reported; denosumab is contraindicated in people with hypocalcemia. Treatment was associated with cataract events in men in the prostate cancer trial.

In the European Union, denosumab is approved for the osteoporosis indication as well as the prostate cancer indication just approved in the United States, according to Amgen.

The Prolia brand of denosumab has been approved as a treatment for bone loss in people receiving hormone ablation therapy for prostate or breast cancer, according to a statement from Amgen, the manufacturer.

The approved indications are for increasing bone mass in women at high risk for fracture on adjuvant aromatase inhibitor therapy for breast cancer and in men at high risk for fracture on androgen deprivation therapy (ADT) for nonmetastatic prostate cancer, the company's statement said.

Denosumab, a RANK ligand inhibitor, was first approved in June 2010 for treating postmenopausal women with osteoporosis at high risk of fracture and is marketed as Prolia for this indication. Prolia is administered in a subcutaneous injection once every 6 months, at a dose of 60 mg.

In November 2010, denosumab was also approved for preventing skeletal-related events in patients with bone metastases from solid tumors. It is marketed as Xgeva and administered more frequently at a higher dose for this indication.

Approval of the new indications for Prolia was based on phase III studies of these two groups of patients, according to Amgen. In an international study of almost 1,500 men with nonmetastatic prostate cancer who were being treated with ADT, bone mineral density at the lumbar spine after 2 years of treatment was significantly higher among men who had received denosumab compared with those who received placebo. After 3 years of treatment, the incidence of new vertebral fractures was 1.5% among those treated with denosumab, compared with 3.9% for those on placebo, a risk reduction of 62%, the company said.

And in a study of 252 postmenopausal women with breast cancer under treatment with an aromatase inhibitor, bone mineral density at the lumbar spine was significantly higher among those treated with denosumab compared with those on placebo after 12 months of treatment, according to the statement.

Arthralgia and back pain were the most common adverse events associated with treatment in these two groups of patients. Hypocalcemia was also reported; denosumab is contraindicated in people with hypocalcemia. Treatment was associated with cataract events in men in the prostate cancer trial.

In the European Union, denosumab is approved for the osteoporosis indication as well as the prostate cancer indication just approved in the United States, according to Amgen.

A review of the potential for prolongation of the QT interval associated with ondansetron has resulted in some "interim" changes to the drug’s label, the Food and Drug Administration announced on Sept. 15.

In a drug safety announcement, the FDA said that the agency conducted a review of all the available information on the risk of QT prolongation with ondansetron and is making the changes, which include recommending against the use of the antinausea drug in patients with congenital long QT syndrome.

Used to prevent nausea and vomiting caused by cancer chemotherapy, radiation therapy, and surgery, ondansetron is a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist marketed as Zofran by GlaxoSmithKline, and is available in generic formulations. Information on the potential for QT prolongation is already included in the label, and QT interval prolongation with ondansetron has been reported in the medical literature, according to the announcement.

But the label will now also recommend ECG monitoring in patients who are treated with ondansetron and have an electrolyte abnormality, congestive heart failure, or bradyarrhythmias, and in patients taking other medications that prolong the QT interval – who are at an increased risk of developing torsades de pointes. QT prolongation can result in the abnormal and potentially fatal heart rhythm torsades de pointes, which has also been reported in patients taking ondansetron, the FDA statement points out.

Patients taking ondansetron should also be advised to contact a health care professional immediately, if they develop signs and symptoms of an abnormal heart rate or rhythm, the statement says.

GlaxoSmithKline is being required by the FDA to conduct a study that will evaluate the potential for ondansetron to prolong the QT interval; results are expected in the summer of 2012. The safety review is ongoing, and "the FDA will continue to assess all available data supporting the safety and effectiveness of ondansetron and will update the public when more information becomes available," the statement said.

The notice is available online. Serious adverse events associated with ondansetron should be reported to the FDA’s MedWatch program at 800-332-1088.

A review of the potential for prolongation of the QT interval associated with ondansetron has resulted in some "interim" changes to the drug’s label, the Food and Drug Administration announced on Sept. 15.

In a drug safety announcement, the FDA said that the agency conducted a review of all the available information on the risk of QT prolongation with ondansetron and is making the changes, which include recommending against the use of the antinausea drug in patients with congenital long QT syndrome.

Used to prevent nausea and vomiting caused by cancer chemotherapy, radiation therapy, and surgery, ondansetron is a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist marketed as Zofran by GlaxoSmithKline, and is available in generic formulations. Information on the potential for QT prolongation is already included in the label, and QT interval prolongation with ondansetron has been reported in the medical literature, according to the announcement.

But the label will now also recommend ECG monitoring in patients who are treated with ondansetron and have an electrolyte abnormality, congestive heart failure, or bradyarrhythmias, and in patients taking other medications that prolong the QT interval – who are at an increased risk of developing torsades de pointes. QT prolongation can result in the abnormal and potentially fatal heart rhythm torsades de pointes, which has also been reported in patients taking ondansetron, the FDA statement points out.

Patients taking ondansetron should also be advised to contact a health care professional immediately, if they develop signs and symptoms of an abnormal heart rate or rhythm, the statement says.

GlaxoSmithKline is being required by the FDA to conduct a study that will evaluate the potential for ondansetron to prolong the QT interval; results are expected in the summer of 2012. The safety review is ongoing, and "the FDA will continue to assess all available data supporting the safety and effectiveness of ondansetron and will update the public when more information becomes available," the statement said.

The notice is available online. Serious adverse events associated with ondansetron should be reported to the FDA’s MedWatch program at 800-332-1088.

A review of the potential for prolongation of the QT interval associated with ondansetron has resulted in some "interim" changes to the drug’s label, the Food and Drug Administration announced on Sept. 15.

In a drug safety announcement, the FDA said that the agency conducted a review of all the available information on the risk of QT prolongation with ondansetron and is making the changes, which include recommending against the use of the antinausea drug in patients with congenital long QT syndrome.

Used to prevent nausea and vomiting caused by cancer chemotherapy, radiation therapy, and surgery, ondansetron is a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist marketed as Zofran by GlaxoSmithKline, and is available in generic formulations. Information on the potential for QT prolongation is already included in the label, and QT interval prolongation with ondansetron has been reported in the medical literature, according to the announcement.

But the label will now also recommend ECG monitoring in patients who are treated with ondansetron and have an electrolyte abnormality, congestive heart failure, or bradyarrhythmias, and in patients taking other medications that prolong the QT interval – who are at an increased risk of developing torsades de pointes. QT prolongation can result in the abnormal and potentially fatal heart rhythm torsades de pointes, which has also been reported in patients taking ondansetron, the FDA statement points out.

Patients taking ondansetron should also be advised to contact a health care professional immediately, if they develop signs and symptoms of an abnormal heart rate or rhythm, the statement says.

GlaxoSmithKline is being required by the FDA to conduct a study that will evaluate the potential for ondansetron to prolong the QT interval; results are expected in the summer of 2012. The safety review is ongoing, and "the FDA will continue to assess all available data supporting the safety and effectiveness of ondansetron and will update the public when more information becomes available," the statement said.

The notice is available online. Serious adverse events associated with ondansetron should be reported to the FDA’s MedWatch program at 800-332-1088.

Venlafaxine and clonidine both outperformed placebo in controlling hot flashes among women with breast cancer in a study published online Sept. 12 in the Journal of Clinical Oncology.

Effective treatments for hot flashes may improve these patients’ ability to continue their anticancer therapies, said Dr. Annelies H. Boekhout of The Netherlands Cancer Institute, Amsterdam, and her associates.

The SSNRI venlafaxine (Effexor) and the antihypertensive clonidine "both are often prescribed treatments and are recommended in clinical guidelines in the management of hot flashes. However, a three-arm trial comparing clonidine, venlafaxine, and placebo in patients with breast cancer has not been conducted" until now, they noted.

In their double-blind study at three Dutch hospitals, 102 women with breast cancer who experienced at least two hot flashes per day were stratified by age, duration of symptoms, concurrent endocrine therapy, and previous chemotherapy, and randomly assigned to receive 75 mg venlafaxine (41 patients), 0.1 mg clonidine (41 patients), or matching placebo (20 patients) daily for 12 weeks.

The women completed daily diaries recording the frequency and severity of hot flashes. They also reported every week on adverse events such as reduced appetite, nausea, sleepiness, dizziness, fatigue, dry mouth, and constipation. They recorded their sleep quality, anxiety, depression, and sexual function at 4 weeks and at the conclusion of treatment.

A total of 22 subjects (22%) either dropped out of the study or were lost to follow-up. Two patients (5%) in the venlafaxine group and six (15%) in the clonidine group cited adverse effects such as somnolence, dizziness, and dry mouth as their reason for discontinuing. Another 9% of patients discontinued because of noncompliance, which "had some effect on the observed differences between treatments in this study."

Among the 35 women assigned to venlafaxine who completed the trial, there was a 42% decline in hot flashes during weeks 1-4, compared with the placebo group. Over the entire study period, the reduction in hot flashes was 41% with venlafaxine, compared with placebo.

Among the 28 women assigned to clonidine who completed the trial, hot flashes declined by only 26% during weeks 1-4 but then declined another 22% during the remainder of the study, for an overall reduction of approximately 45%.

Thus, both active agents decreased the frequency and severity of hot flashes compared with placebo, with no discernible difference between the two by week 12. "A more rapid reduction of hot flashes suggests that venlafaxine is to be preferred over clonidine," Dr. Boekhout and her colleagues said (J. Clin. Oncol. 2011 Sept. 12 [doi:10.1200/JCO.2010.33.1298]).

They added that it is "advisable to treat patients to manage hot flashes with venlafaxine 37.5 mg daily in the first week and increase the venlafaxine dose to 75 mg if greater efficacy is desired."

A total of 14 patients (34%) in the clonidine group, 23 (56%) in the venlafaxine group, and 4 (20%) in the placebo group said they wished to continue the study treatment at the end of the trial.

Women taking clonidine reported more symptoms of anxiety and women taking venlafaxine reported more symptoms of depression. Sexual function and sleep quality did not differ between the two groups. However, the duration of this study may have been too short to adequately assess these adverse effects, the researchers noted.

No conflicts of interest were reported.

Venlafaxine and clonidine both outperformed placebo in controlling hot flashes among women with breast cancer in a study published online Sept. 12 in the Journal of Clinical Oncology.

Effective treatments for hot flashes may improve these patients’ ability to continue their anticancer therapies, said Dr. Annelies H. Boekhout of The Netherlands Cancer Institute, Amsterdam, and her associates.

The SSNRI venlafaxine (Effexor) and the antihypertensive clonidine "both are often prescribed treatments and are recommended in clinical guidelines in the management of hot flashes. However, a three-arm trial comparing clonidine, venlafaxine, and placebo in patients with breast cancer has not been conducted" until now, they noted.

In their double-blind study at three Dutch hospitals, 102 women with breast cancer who experienced at least two hot flashes per day were stratified by age, duration of symptoms, concurrent endocrine therapy, and previous chemotherapy, and randomly assigned to receive 75 mg venlafaxine (41 patients), 0.1 mg clonidine (41 patients), or matching placebo (20 patients) daily for 12 weeks.

The women completed daily diaries recording the frequency and severity of hot flashes. They also reported every week on adverse events such as reduced appetite, nausea, sleepiness, dizziness, fatigue, dry mouth, and constipation. They recorded their sleep quality, anxiety, depression, and sexual function at 4 weeks and at the conclusion of treatment.

A total of 22 subjects (22%) either dropped out of the study or were lost to follow-up. Two patients (5%) in the venlafaxine group and six (15%) in the clonidine group cited adverse effects such as somnolence, dizziness, and dry mouth as their reason for discontinuing. Another 9% of patients discontinued because of noncompliance, which "had some effect on the observed differences between treatments in this study."

Among the 35 women assigned to venlafaxine who completed the trial, there was a 42% decline in hot flashes during weeks 1-4, compared with the placebo group. Over the entire study period, the reduction in hot flashes was 41% with venlafaxine, compared with placebo.

Among the 28 women assigned to clonidine who completed the trial, hot flashes declined by only 26% during weeks 1-4 but then declined another 22% during the remainder of the study, for an overall reduction of approximately 45%.

Thus, both active agents decreased the frequency and severity of hot flashes compared with placebo, with no discernible difference between the two by week 12. "A more rapid reduction of hot flashes suggests that venlafaxine is to be preferred over clonidine," Dr. Boekhout and her colleagues said (J. Clin. Oncol. 2011 Sept. 12 [doi:10.1200/JCO.2010.33.1298]).

They added that it is "advisable to treat patients to manage hot flashes with venlafaxine 37.5 mg daily in the first week and increase the venlafaxine dose to 75 mg if greater efficacy is desired."

A total of 14 patients (34%) in the clonidine group, 23 (56%) in the venlafaxine group, and 4 (20%) in the placebo group said they wished to continue the study treatment at the end of the trial.

Women taking clonidine reported more symptoms of anxiety and women taking venlafaxine reported more symptoms of depression. Sexual function and sleep quality did not differ between the two groups. However, the duration of this study may have been too short to adequately assess these adverse effects, the researchers noted.

No conflicts of interest were reported.

Venlafaxine and clonidine both outperformed placebo in controlling hot flashes among women with breast cancer in a study published online Sept. 12 in the Journal of Clinical Oncology.

Effective treatments for hot flashes may improve these patients’ ability to continue their anticancer therapies, said Dr. Annelies H. Boekhout of The Netherlands Cancer Institute, Amsterdam, and her associates.

The SSNRI venlafaxine (Effexor) and the antihypertensive clonidine "both are often prescribed treatments and are recommended in clinical guidelines in the management of hot flashes. However, a three-arm trial comparing clonidine, venlafaxine, and placebo in patients with breast cancer has not been conducted" until now, they noted.

In their double-blind study at three Dutch hospitals, 102 women with breast cancer who experienced at least two hot flashes per day were stratified by age, duration of symptoms, concurrent endocrine therapy, and previous chemotherapy, and randomly assigned to receive 75 mg venlafaxine (41 patients), 0.1 mg clonidine (41 patients), or matching placebo (20 patients) daily for 12 weeks.

The women completed daily diaries recording the frequency and severity of hot flashes. They also reported every week on adverse events such as reduced appetite, nausea, sleepiness, dizziness, fatigue, dry mouth, and constipation. They recorded their sleep quality, anxiety, depression, and sexual function at 4 weeks and at the conclusion of treatment.

A total of 22 subjects (22%) either dropped out of the study or were lost to follow-up. Two patients (5%) in the venlafaxine group and six (15%) in the clonidine group cited adverse effects such as somnolence, dizziness, and dry mouth as their reason for discontinuing. Another 9% of patients discontinued because of noncompliance, which "had some effect on the observed differences between treatments in this study."

Among the 35 women assigned to venlafaxine who completed the trial, there was a 42% decline in hot flashes during weeks 1-4, compared with the placebo group. Over the entire study period, the reduction in hot flashes was 41% with venlafaxine, compared with placebo.

Among the 28 women assigned to clonidine who completed the trial, hot flashes declined by only 26% during weeks 1-4 but then declined another 22% during the remainder of the study, for an overall reduction of approximately 45%.

Thus, both active agents decreased the frequency and severity of hot flashes compared with placebo, with no discernible difference between the two by week 12. "A more rapid reduction of hot flashes suggests that venlafaxine is to be preferred over clonidine," Dr. Boekhout and her colleagues said (J. Clin. Oncol. 2011 Sept. 12 [doi:10.1200/JCO.2010.33.1298]).

They added that it is "advisable to treat patients to manage hot flashes with venlafaxine 37.5 mg daily in the first week and increase the venlafaxine dose to 75 mg if greater efficacy is desired."

A total of 14 patients (34%) in the clonidine group, 23 (56%) in the venlafaxine group, and 4 (20%) in the placebo group said they wished to continue the study treatment at the end of the trial.

Women taking clonidine reported more symptoms of anxiety and women taking venlafaxine reported more symptoms of depression. Sexual function and sleep quality did not differ between the two groups. However, the duration of this study may have been too short to adequately assess these adverse effects, the researchers noted.

No conflicts of interest were reported.

ADELPHI, MD. – Data on the safety and effectiveness of bisphosphonate drugs for the long-term treatment of osteoporosis is lacking and direly needed, according to a joint Food and Drug Administration advisory committee meeting.

Specifically, the Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted 17-6 on Sept. 9 that labeling for these drugs should be changed to clarify the duration of use for this drug class.

The agency convened the joint meeting to evaluate particular concerns about the long-term use bisphosphonate drugs, given reports of atypical subtrochanteric and femoral fractures, jaw osteonecrosis, and esophageal cancer associated with bisphosphonate use.

The labels of bisphosphonate drugs – alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva), and zoledronic acid (Reclast) – already include "important limitation of use" information. This labeling states that the optimal duration of treatment (for an individual drug) has not been determined and that all patients on bisphosphonate therapy should be periodically reassessed for the necessity of continued therapy.

While the panel voted to clarify the label language, they were emphatic that much more data are needed to establish the long-term efficacy and safety of bisphosphonates in general and with special regard to atypical fractures, jaw osteonecrosis, and esophageal cancer.

The two committees also were asked to assess the strength of data on the long-term use of bisphosphonates; the overall risks and benefits of continuous long-term use (3-5 years or more); whether restricting the duration of use or implementing a drug holiday would be beneficial; which outcomes require further evidence; and how should this data be obtained.

The expert consensus is that existing data – some of which go out to roughly 10 years for one drug – do not address the efficacy of the long-term use of bisphosphonates. They recommended that (in no particular order) additional data are needed with regard to the occurrence of atypical fractures, osteonecrosis of the jaw, esophageal cancer, osteoporotic fracture reduction efficacy with long-term (at least 3-5 years) continuous bisphosphonate use, and the effect of a "drug holiday" on drug safety and effectiveness.

Osteoporosis currently affects approximately 10 million Americans, according to the American Society for Bone and Mineral Research. An additional 34 million have low bone mass, which may progress to osteoporosis.

Panelists have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally a panelist may be given a waiver, but none were given at this meeting.

ADELPHI, MD. – Data on the safety and effectiveness of bisphosphonate drugs for the long-term treatment of osteoporosis is lacking and direly needed, according to a joint Food and Drug Administration advisory committee meeting.

Specifically, the Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted 17-6 on Sept. 9 that labeling for these drugs should be changed to clarify the duration of use for this drug class.

The agency convened the joint meeting to evaluate particular concerns about the long-term use bisphosphonate drugs, given reports of atypical subtrochanteric and femoral fractures, jaw osteonecrosis, and esophageal cancer associated with bisphosphonate use.

The labels of bisphosphonate drugs – alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva), and zoledronic acid (Reclast) – already include "important limitation of use" information. This labeling states that the optimal duration of treatment (for an individual drug) has not been determined and that all patients on bisphosphonate therapy should be periodically reassessed for the necessity of continued therapy.

While the panel voted to clarify the label language, they were emphatic that much more data are needed to establish the long-term efficacy and safety of bisphosphonates in general and with special regard to atypical fractures, jaw osteonecrosis, and esophageal cancer.

The two committees also were asked to assess the strength of data on the long-term use of bisphosphonates; the overall risks and benefits of continuous long-term use (3-5 years or more); whether restricting the duration of use or implementing a drug holiday would be beneficial; which outcomes require further evidence; and how should this data be obtained.

The expert consensus is that existing data – some of which go out to roughly 10 years for one drug – do not address the efficacy of the long-term use of bisphosphonates. They recommended that (in no particular order) additional data are needed with regard to the occurrence of atypical fractures, osteonecrosis of the jaw, esophageal cancer, osteoporotic fracture reduction efficacy with long-term (at least 3-5 years) continuous bisphosphonate use, and the effect of a "drug holiday" on drug safety and effectiveness.

Osteoporosis currently affects approximately 10 million Americans, according to the American Society for Bone and Mineral Research. An additional 34 million have low bone mass, which may progress to osteoporosis.

Panelists have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally a panelist may be given a waiver, but none were given at this meeting.

ADELPHI, MD. – Data on the safety and effectiveness of bisphosphonate drugs for the long-term treatment of osteoporosis is lacking and direly needed, according to a joint Food and Drug Administration advisory committee meeting.

Specifically, the Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted 17-6 on Sept. 9 that labeling for these drugs should be changed to clarify the duration of use for this drug class.

The agency convened the joint meeting to evaluate particular concerns about the long-term use bisphosphonate drugs, given reports of atypical subtrochanteric and femoral fractures, jaw osteonecrosis, and esophageal cancer associated with bisphosphonate use.

The labels of bisphosphonate drugs – alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva), and zoledronic acid (Reclast) – already include "important limitation of use" information. This labeling states that the optimal duration of treatment (for an individual drug) has not been determined and that all patients on bisphosphonate therapy should be periodically reassessed for the necessity of continued therapy.

While the panel voted to clarify the label language, they were emphatic that much more data are needed to establish the long-term efficacy and safety of bisphosphonates in general and with special regard to atypical fractures, jaw osteonecrosis, and esophageal cancer.

The two committees also were asked to assess the strength of data on the long-term use of bisphosphonates; the overall risks and benefits of continuous long-term use (3-5 years or more); whether restricting the duration of use or implementing a drug holiday would be beneficial; which outcomes require further evidence; and how should this data be obtained.

The expert consensus is that existing data – some of which go out to roughly 10 years for one drug – do not address the efficacy of the long-term use of bisphosphonates. They recommended that (in no particular order) additional data are needed with regard to the occurrence of atypical fractures, osteonecrosis of the jaw, esophageal cancer, osteoporotic fracture reduction efficacy with long-term (at least 3-5 years) continuous bisphosphonate use, and the effect of a "drug holiday" on drug safety and effectiveness.

Osteoporosis currently affects approximately 10 million Americans, according to the American Society for Bone and Mineral Research. An additional 34 million have low bone mass, which may progress to osteoporosis.

Panelists have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally a panelist may be given a waiver, but none were given at this meeting.

A new set of nomograms based on easily assessed risk factors accurately predicts a woman’s likelihood of developing lymphedema after axillary lymph node dissection for breast cancer, researchers are reporting at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

The nomograms, which enable risk assessment throughout the course of treatment using data available at the time, had accuracy exceeding 70%, according to results presented in a press briefing before the meeting.

"The accuracy is the same as mammography to detect breast cancer. ... So that’s a very good statistical tool," said lead author Dr. Jose Bevilacqua, a surgical oncologist at the Hospital Sirio-Libanês in São Paulo, Brazil.

Being able to identify high-risk patients has several potential applications, he added. They could be monitored more closely and offered interventions that might prevent or reduce the severity of lymphedema, such as use of compression sleeves. "The earlier you detect [it], the better is the outcome," Dr. Bevilacqua said.

Additionally, high-risk patients with a positive sentinel lymph node could be counseled about the risk of further surgery. Thus, "you have physicians who make closer follow-up and [have] a better discussion with the patients."

Finally, the nomograms could be applied in clinical research. "These tools might help [ongoing] or new studies to select high-risk patients in order to avoid exposing the low-risk patients to unproven therapies," he explained.

Dr. Andrew Seidman, moderator of the press briefing and a medical oncologist at the Memorial Sloan-Kettering Cancer Center in New York, commended the investigators for a study that "has real practical implications for patients."

"It allows us to identify patients who then can be appropriately triaged for early intervention and perhaps for clinical trials aimed at preventing what many consider inevitable, and that is the development of lymphedema."

The effectiveness of early interventions is controversial, according to Dr. Seidman, who did not report any relevant conflicts of interest. "There are believers and there are nonbelievers," he commented. "What I think this nomogram does is [allow] us in a scientific way to segregate out patients in terms of their risk, and by doing that, we can have more uniform cohorts for which early intervention can be studied more rigorously."

The researchers prospectively followed 1,054 women with unilateral breast cancer who underwent breast-conserving surgery or mastectomy with an axillary lymph node dissection in 2001-2002. Median follow-up was 41 months.

"As far as we know, we have established the largest prospective cohort specifically established to study the incidence and factors associated with lymphedema after axillary node dissection for breast cancer," commented Dr. Bevilacqua.

Using Data to Predict Lymphedema

The women had serial arm volume measurements starting before surgery. To facilitate this process, the researchers created a tool that is now available free online (www.armvolume.com).

They then developed and internally validated three multivariate nomograms (or statistical models) for predicting lymphedema using data available at various time points.

The first model, to be used preoperatively, incorporated age, body mass index, and number of cycles of neoadjuvant chemotherapy infusions in the ipsilateral arm.

The second model, to be used within the first 6 months after surgery, incorporated all the factors from the first plus the extent of axillary dissection, the location of radiation therapy field, and the number of cycles of adjuvant chemotherapy infusions in the ipsilateral arm.

The third model, to be used 6 months or later after surgery, incorporated all the factors from the second, plus the development of postoperative seroma and development of early edema.

Study results showed that within 5 years of axillary lymph node dissection, 30.3% of the women developed lymphedema (defined as a difference in volume of at least 200 mL between arms at 6 months or later after surgery).

All of the risk factors used in the models were significantly associated with the development of lymphedema, Dr. Bevilacqua reported.

"One of the novelties of our study is the [finding] that ipsilateral neoadjuvant chemotherapy infusion is as morbid as adjuvant chemotherapy infusion to increase the risk of lymphedema," he pointed out. "This is somewhat intuitive, but it has never been described, and the great majority of clinical oncologists are not aware of this fact."

For predicting the 5-year risk of lymphedema, the first, second, and third models had accuracy of 70.6%, 72.9%, and 73.6%, respectively. The investigators have converted the models into free, user-friendly calculators that are available online (www.lymphedemarisk.com) during the ASCO Breast Cancer Symposium (Sept. 8-10), but will be taken off line until the manuscript is published, after which they are to become available again.

Dr. Bevilacqua reported that he had no relevant conflicts of interest.

A new set of nomograms based on easily assessed risk factors accurately predicts a woman’s likelihood of developing lymphedema after axillary lymph node dissection for breast cancer, researchers are reporting at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

The nomograms, which enable risk assessment throughout the course of treatment using data available at the time, had accuracy exceeding 70%, according to results presented in a press briefing before the meeting.

"The accuracy is the same as mammography to detect breast cancer. ... So that’s a very good statistical tool," said lead author Dr. Jose Bevilacqua, a surgical oncologist at the Hospital Sirio-Libanês in São Paulo, Brazil.

Being able to identify high-risk patients has several potential applications, he added. They could be monitored more closely and offered interventions that might prevent or reduce the severity of lymphedema, such as use of compression sleeves. "The earlier you detect [it], the better is the outcome," Dr. Bevilacqua said.

Additionally, high-risk patients with a positive sentinel lymph node could be counseled about the risk of further surgery. Thus, "you have physicians who make closer follow-up and [have] a better discussion with the patients."

Finally, the nomograms could be applied in clinical research. "These tools might help [ongoing] or new studies to select high-risk patients in order to avoid exposing the low-risk patients to unproven therapies," he explained.

Dr. Andrew Seidman, moderator of the press briefing and a medical oncologist at the Memorial Sloan-Kettering Cancer Center in New York, commended the investigators for a study that "has real practical implications for patients."

"It allows us to identify patients who then can be appropriately triaged for early intervention and perhaps for clinical trials aimed at preventing what many consider inevitable, and that is the development of lymphedema."

The effectiveness of early interventions is controversial, according to Dr. Seidman, who did not report any relevant conflicts of interest. "There are believers and there are nonbelievers," he commented. "What I think this nomogram does is [allow] us in a scientific way to segregate out patients in terms of their risk, and by doing that, we can have more uniform cohorts for which early intervention can be studied more rigorously."

The researchers prospectively followed 1,054 women with unilateral breast cancer who underwent breast-conserving surgery or mastectomy with an axillary lymph node dissection in 2001-2002. Median follow-up was 41 months.

"As far as we know, we have established the largest prospective cohort specifically established to study the incidence and factors associated with lymphedema after axillary node dissection for breast cancer," commented Dr. Bevilacqua.

Using Data to Predict Lymphedema

The women had serial arm volume measurements starting before surgery. To facilitate this process, the researchers created a tool that is now available free online (www.armvolume.com).

They then developed and internally validated three multivariate nomograms (or statistical models) for predicting lymphedema using data available at various time points.

The first model, to be used preoperatively, incorporated age, body mass index, and number of cycles of neoadjuvant chemotherapy infusions in the ipsilateral arm.

The second model, to be used within the first 6 months after surgery, incorporated all the factors from the first plus the extent of axillary dissection, the location of radiation therapy field, and the number of cycles of adjuvant chemotherapy infusions in the ipsilateral arm.

The third model, to be used 6 months or later after surgery, incorporated all the factors from the second, plus the development of postoperative seroma and development of early edema.

Study results showed that within 5 years of axillary lymph node dissection, 30.3% of the women developed lymphedema (defined as a difference in volume of at least 200 mL between arms at 6 months or later after surgery).

All of the risk factors used in the models were significantly associated with the development of lymphedema, Dr. Bevilacqua reported.

"One of the novelties of our study is the [finding] that ipsilateral neoadjuvant chemotherapy infusion is as morbid as adjuvant chemotherapy infusion to increase the risk of lymphedema," he pointed out. "This is somewhat intuitive, but it has never been described, and the great majority of clinical oncologists are not aware of this fact."

For predicting the 5-year risk of lymphedema, the first, second, and third models had accuracy of 70.6%, 72.9%, and 73.6%, respectively. The investigators have converted the models into free, user-friendly calculators that are available online (www.lymphedemarisk.com) during the ASCO Breast Cancer Symposium (Sept. 8-10), but will be taken off line until the manuscript is published, after which they are to become available again.

Dr. Bevilacqua reported that he had no relevant conflicts of interest.

A new set of nomograms based on easily assessed risk factors accurately predicts a woman’s likelihood of developing lymphedema after axillary lymph node dissection for breast cancer, researchers are reporting at a breast cancer symposium sponsored by the American Society of Clinical Oncology.

The nomograms, which enable risk assessment throughout the course of treatment using data available at the time, had accuracy exceeding 70%, according to results presented in a press briefing before the meeting.

"The accuracy is the same as mammography to detect breast cancer. ... So that’s a very good statistical tool," said lead author Dr. Jose Bevilacqua, a surgical oncologist at the Hospital Sirio-Libanês in São Paulo, Brazil.

Being able to identify high-risk patients has several potential applications, he added. They could be monitored more closely and offered interventions that might prevent or reduce the severity of lymphedema, such as use of compression sleeves. "The earlier you detect [it], the better is the outcome," Dr. Bevilacqua said.

Additionally, high-risk patients with a positive sentinel lymph node could be counseled about the risk of further surgery. Thus, "you have physicians who make closer follow-up and [have] a better discussion with the patients."

Finally, the nomograms could be applied in clinical research. "These tools might help [ongoing] or new studies to select high-risk patients in order to avoid exposing the low-risk patients to unproven therapies," he explained.

Dr. Andrew Seidman, moderator of the press briefing and a medical oncologist at the Memorial Sloan-Kettering Cancer Center in New York, commended the investigators for a study that "has real practical implications for patients."

"It allows us to identify patients who then can be appropriately triaged for early intervention and perhaps for clinical trials aimed at preventing what many consider inevitable, and that is the development of lymphedema."

The effectiveness of early interventions is controversial, according to Dr. Seidman, who did not report any relevant conflicts of interest. "There are believers and there are nonbelievers," he commented. "What I think this nomogram does is [allow] us in a scientific way to segregate out patients in terms of their risk, and by doing that, we can have more uniform cohorts for which early intervention can be studied more rigorously."

The researchers prospectively followed 1,054 women with unilateral breast cancer who underwent breast-conserving surgery or mastectomy with an axillary lymph node dissection in 2001-2002. Median follow-up was 41 months.

"As far as we know, we have established the largest prospective cohort specifically established to study the incidence and factors associated with lymphedema after axillary node dissection for breast cancer," commented Dr. Bevilacqua.

Using Data to Predict Lymphedema

The women had serial arm volume measurements starting before surgery. To facilitate this process, the researchers created a tool that is now available free online (www.armvolume.com).

They then developed and internally validated three multivariate nomograms (or statistical models) for predicting lymphedema using data available at various time points.

The first model, to be used preoperatively, incorporated age, body mass index, and number of cycles of neoadjuvant chemotherapy infusions in the ipsilateral arm.

The second model, to be used within the first 6 months after surgery, incorporated all the factors from the first plus the extent of axillary dissection, the location of radiation therapy field, and the number of cycles of adjuvant chemotherapy infusions in the ipsilateral arm.

The third model, to be used 6 months or later after surgery, incorporated all the factors from the second, plus the development of postoperative seroma and development of early edema.

Study results showed that within 5 years of axillary lymph node dissection, 30.3% of the women developed lymphedema (defined as a difference in volume of at least 200 mL between arms at 6 months or later after surgery).

All of the risk factors used in the models were significantly associated with the development of lymphedema, Dr. Bevilacqua reported.

"One of the novelties of our study is the [finding] that ipsilateral neoadjuvant chemotherapy infusion is as morbid as adjuvant chemotherapy infusion to increase the risk of lymphedema," he pointed out. "This is somewhat intuitive, but it has never been described, and the great majority of clinical oncologists are not aware of this fact."

For predicting the 5-year risk of lymphedema, the first, second, and third models had accuracy of 70.6%, 72.9%, and 73.6%, respectively. The investigators have converted the models into free, user-friendly calculators that are available online (www.lymphedemarisk.com) during the ASCO Breast Cancer Symposium (Sept. 8-10), but will be taken off line until the manuscript is published, after which they are to become available again.

Dr. Bevilacqua reported that he had no relevant conflicts of interest.

Bisphosponate-related osteonecrosis of the jaw (ONJ) has been reported in the literature since 2003,1,2 with more than 90% of the events attributed to treatment with bisphosphonate agents, such as zoledronic acid (Zometa) and pamidronate, which are used to treat hypercalcemia of malignancy and to reduce the risk of skeletal-related events due to bone metastases.3– 5 Patients with ONJ generally present with exposed necrotic bone that does not heal for 6–8 weeks, often leading to significant morbidity. The pathogenic mechanism for osteonecrosis is unclear, but, in addition to inhibiting bone resorption, preclinical data have demonstrated thrombotic microangiopathy and potent inhibition of angiogenesis,6 which may lead to avascular necrosis and poor wound healing after dental procedures.

Angiogenesis is a critical step in tumor growth, and agents that block neovascularization by targeting vascular endothelial growth factor (VEGF) or its receptor (VEGFR) have been used successfully for a variety of solid tumors. Bevacizumab (Avastin) is a monoclonal antibody that inhibits angiogenesis by binding to VEGF,7 and sorafenib (Nexavar) is a multiple-kinase inhibitor that inhibits several intracellular and cell-surface kinases, including VEGFR.8 Osteonecrosis of the jaw or femoral heads has been increasingly recognized in patients treated with antiangiogenic therapies, even without concurrent bisphosphonate use.9–12 Previous data on combining bisphosphonates with antiangiogenic agents are conflicting, with some reports indicating a similar risk of ONJ compared with the use of bisphosphonates alone13,14 and others showing significantly higher rates (18% vs 1% with bisphosphonates alone).15.16

In this paper, we describe the case of a patient with metastatic prostate cancer and a history of ONJ from use of zoledronic acid who developed a mandibular fracture while he was off zoledronic acid for 15 months but undergoing treatment with paclitaxel and bevacizumab plus sorafenib on a clinical trial. The case may help explain the temporal relationship between therapy and the occurrence of jaw fracture, as well as the link between ONJ and the risk of fractures with sequential use of bisphosphonates and antiangiogenic agents. ...

* For a PDF of the full article, click in the link to the left of this introduction.

Bisphosponate-related osteonecrosis of the jaw (ONJ) has been reported in the literature since 2003,1,2 with more than 90% of the events attributed to treatment with bisphosphonate agents, such as zoledronic acid (Zometa) and pamidronate, which are used to treat hypercalcemia of malignancy and to reduce the risk of skeletal-related events due to bone metastases.3– 5 Patients with ONJ generally present with exposed necrotic bone that does not heal for 6–8 weeks, often leading to significant morbidity. The pathogenic mechanism for osteonecrosis is unclear, but, in addition to inhibiting bone resorption, preclinical data have demonstrated thrombotic microangiopathy and potent inhibition of angiogenesis,6 which may lead to avascular necrosis and poor wound healing after dental procedures.

Angiogenesis is a critical step in tumor growth, and agents that block neovascularization by targeting vascular endothelial growth factor (VEGF) or its receptor (VEGFR) have been used successfully for a variety of solid tumors. Bevacizumab (Avastin) is a monoclonal antibody that inhibits angiogenesis by binding to VEGF,7 and sorafenib (Nexavar) is a multiple-kinase inhibitor that inhibits several intracellular and cell-surface kinases, including VEGFR.8 Osteonecrosis of the jaw or femoral heads has been increasingly recognized in patients treated with antiangiogenic therapies, even without concurrent bisphosphonate use.9–12 Previous data on combining bisphosphonates with antiangiogenic agents are conflicting, with some reports indicating a similar risk of ONJ compared with the use of bisphosphonates alone13,14 and others showing significantly higher rates (18% vs 1% with bisphosphonates alone).15.16

In this paper, we describe the case of a patient with metastatic prostate cancer and a history of ONJ from use of zoledronic acid who developed a mandibular fracture while he was off zoledronic acid for 15 months but undergoing treatment with paclitaxel and bevacizumab plus sorafenib on a clinical trial. The case may help explain the temporal relationship between therapy and the occurrence of jaw fracture, as well as the link between ONJ and the risk of fractures with sequential use of bisphosphonates and antiangiogenic agents. ...

* For a PDF of the full article, click in the link to the left of this introduction.

Bisphosponate-related osteonecrosis of the jaw (ONJ) has been reported in the literature since 2003,1,2 with more than 90% of the events attributed to treatment with bisphosphonate agents, such as zoledronic acid (Zometa) and pamidronate, which are used to treat hypercalcemia of malignancy and to reduce the risk of skeletal-related events due to bone metastases.3– 5 Patients with ONJ generally present with exposed necrotic bone that does not heal for 6–8 weeks, often leading to significant morbidity. The pathogenic mechanism for osteonecrosis is unclear, but, in addition to inhibiting bone resorption, preclinical data have demonstrated thrombotic microangiopathy and potent inhibition of angiogenesis,6 which may lead to avascular necrosis and poor wound healing after dental procedures.

Angiogenesis is a critical step in tumor growth, and agents that block neovascularization by targeting vascular endothelial growth factor (VEGF) or its receptor (VEGFR) have been used successfully for a variety of solid tumors. Bevacizumab (Avastin) is a monoclonal antibody that inhibits angiogenesis by binding to VEGF,7 and sorafenib (Nexavar) is a multiple-kinase inhibitor that inhibits several intracellular and cell-surface kinases, including VEGFR.8 Osteonecrosis of the jaw or femoral heads has been increasingly recognized in patients treated with antiangiogenic therapies, even without concurrent bisphosphonate use.9–12 Previous data on combining bisphosphonates with antiangiogenic agents are conflicting, with some reports indicating a similar risk of ONJ compared with the use of bisphosphonates alone13,14 and others showing significantly higher rates (18% vs 1% with bisphosphonates alone).15.16

In this paper, we describe the case of a patient with metastatic prostate cancer and a history of ONJ from use of zoledronic acid who developed a mandibular fracture while he was off zoledronic acid for 15 months but undergoing treatment with paclitaxel and bevacizumab plus sorafenib on a clinical trial. The case may help explain the temporal relationship between therapy and the occurrence of jaw fracture, as well as the link between ONJ and the risk of fractures with sequential use of bisphosphonates and antiangiogenic agents. ...

* For a PDF of the full article, click in the link to the left of this introduction.

Everyone in community oncology practice has a role to play in the delivery of quality care. If you are looking to implement a quality program, each member of the practice, patients included, should be involved in the planning, implementing, reporting, and revising processes. Once those processes are in place, the practice can set up partnerships with payers based on standardized measures, costs, and outcomes, with appropriate payments.

Click on the PDF icon at the top of this introduction to read the full article.

Everyone in community oncology practice has a role to play in the delivery of quality care. If you are looking to implement a quality program, each member of the practice, patients included, should be involved in the planning, implementing, reporting, and revising processes. Once those processes are in place, the practice can set up partnerships with payers based on standardized measures, costs, and outcomes, with appropriate payments.

Click on the PDF icon at the top of this introduction to read the full article.

Everyone in community oncology practice has a role to play in the delivery of quality care. If you are looking to implement a quality program, each member of the practice, patients included, should be involved in the planning, implementing, reporting, and revising processes. Once those processes are in place, the practice can set up partnerships with payers based on standardized measures, costs, and outcomes, with appropriate payments.

Click on the PDF icon at the top of this introduction to read the full article.

BETHESDA, MD. – Palliative care, once limited to the last days before death, is ripe for research and essential to improving patient quality of life, according to speakers at a summit sponsored by the National Institute of Nursing Research and National Institutes of Health partners.

"We have to put the clinician back in the mix," Dr. Ira R. Byock, professor of anesthesiology and director of palliative medicine at Dartmouth Medical School in Hanover, N.H., said in the opening keynote address.

According to several speakers at the meeting, putting the clinician back in the mix may mean changing the thinking about palliative care from something that begins in the last days of life to something started as early as a patient’s first day of a cancer diagnosis, as well as making it easier for clinicians to explore palliative care strategies.

One route to improving palliative care is through rigorous research in both inpatient and outpatient settings to see what works, according to Dr. Jennifer S. Temel, clinical director of thoracic oncology at Massachusetts General Hospital in Boston.

Dr. Temel made the case for the value of palliative care research when she discussed her recent study of early palliative care for patients with advanced lung cancer (N. Engl. J. Med. 2010;363:733-42).

Chemotherapy can improve symptoms, "but the problem is that patients are trading off their cancer symptoms for chemotherapy-related symptoms (fatigue, nausea, neuropathy), so overall physical quality of life is not significantly changed," she said.

In a randomized, controlled trial of 151 adults with metastatic non–small cell lung cancer, patients who received palliative care soon after their diagnoses had significantly less depression and anxiety, compared with controls. Another significant finding: The median survival was longer among patients in the early palliative care group, compared with controls (11.6 months vs. 8.9 months; P = .02).

Patients with advanced illnesses suffer from both physical and psychological symptoms, Dr. Temel said.

Dr. Temel’s findings suggest that early palliative care can be used in conjunction with chemotherapy, and cancer patients could be managed jointly in an oncology and clinic setting. However, more research is needed to support and expand her findings.

To help promote and enhance additional research in the field of palliative care, Dr. Amy P. Abernethy, an oncologist at Duke University Medical Center in Durham, N.C., described the creation of the U.S. Palliative Care Research Cooperative (PCRC) group. Dr. Abernethy is the coprincipal investigator of the PCRC, which was established in 2010 and funded by the National Institute of Nursing Research. The PCRC is currently establishing research protocols and procedures through which palliative care researchers will be able to suggest topics and submit grant applications, said Dr. Abernethy. "We must focus our scope, choose studies carefully, and do them well," she said.

The need to engage patients and caregivers as partners in palliative care research was addressed in many talks, as was the need for better communication among clinicians, patients, and caregivers about palliative care. Dianne Gray, a parent advocate whose young son died of a rare genetic disease, spoke about the importance of communication between doctors and patients facing end-of-life issues and reminded clinicians that families want to work with doctors. But families also want honesty, even if the answer is "I don’t know," she emphasized.

In the summit’s closing keynote address, Dr. J. Randall Curtis, director of the Harborview/University of Washington End-of-Life Care Research Program, Seattle, discussed how changing attitudes toward palliative are getting clinicians back in the mix.

"Palliative care is much more broadly accepted as an important part of health care" in both inpatient and outpatient settings, he said in an interview.

Palliative care applies to all patients who face a life-limiting illness or a chronic illness that may shorten life, whether they are actively dying or only starting to manage an illness or think about end-of-life care, he said.

"Hospital-based physicians in particular have a very important role in providing palliative care," said Dr. Curtis. They have the opportunity to introduce discussions of palliative care when patients are hospitalized for exacerbation of symptoms, or when they are hospitalized in the last stages of life, he noted.

"I think there is a growing realization that all physicians caring for patients with life-limiting or life-threatening illnesses need to have basic palliative care skills," although specialists can and should be called in for difficult cases, Dr. Curtis said.

Dr. Temel said she had no financial conflicts to disclose. Dr. Curtis has received funding from the National Institutes of Health and the National Institute of Nursing Research. The summit was sponsored in part by the Foundation for the National Institutes of Health and by Pfizer.

BETHESDA, MD. – Palliative care, once limited to the last days before death, is ripe for research and essential to improving patient quality of life, according to speakers at a summit sponsored by the National Institute of Nursing Research and National Institutes of Health partners.

"We have to put the clinician back in the mix," Dr. Ira R. Byock, professor of anesthesiology and director of palliative medicine at Dartmouth Medical School in Hanover, N.H., said in the opening keynote address.

According to several speakers at the meeting, putting the clinician back in the mix may mean changing the thinking about palliative care from something that begins in the last days of life to something started as early as a patient’s first day of a cancer diagnosis, as well as making it easier for clinicians to explore palliative care strategies.

One route to improving palliative care is through rigorous research in both inpatient and outpatient settings to see what works, according to Dr. Jennifer S. Temel, clinical director of thoracic oncology at Massachusetts General Hospital in Boston.

Dr. Temel made the case for the value of palliative care research when she discussed her recent study of early palliative care for patients with advanced lung cancer (N. Engl. J. Med. 2010;363:733-42).

Chemotherapy can improve symptoms, "but the problem is that patients are trading off their cancer symptoms for chemotherapy-related symptoms (fatigue, nausea, neuropathy), so overall physical quality of life is not significantly changed," she said.

In a randomized, controlled trial of 151 adults with metastatic non–small cell lung cancer, patients who received palliative care soon after their diagnoses had significantly less depression and anxiety, compared with controls. Another significant finding: The median survival was longer among patients in the early palliative care group, compared with controls (11.6 months vs. 8.9 months; P = .02).

Patients with advanced illnesses suffer from both physical and psychological symptoms, Dr. Temel said.

Dr. Temel’s findings suggest that early palliative care can be used in conjunction with chemotherapy, and cancer patients could be managed jointly in an oncology and clinic setting. However, more research is needed to support and expand her findings.

To help promote and enhance additional research in the field of palliative care, Dr. Amy P. Abernethy, an oncologist at Duke University Medical Center in Durham, N.C., described the creation of the U.S. Palliative Care Research Cooperative (PCRC) group. Dr. Abernethy is the coprincipal investigator of the PCRC, which was established in 2010 and funded by the National Institute of Nursing Research. The PCRC is currently establishing research protocols and procedures through which palliative care researchers will be able to suggest topics and submit grant applications, said Dr. Abernethy. "We must focus our scope, choose studies carefully, and do them well," she said.

The need to engage patients and caregivers as partners in palliative care research was addressed in many talks, as was the need for better communication among clinicians, patients, and caregivers about palliative care. Dianne Gray, a parent advocate whose young son died of a rare genetic disease, spoke about the importance of communication between doctors and patients facing end-of-life issues and reminded clinicians that families want to work with doctors. But families also want honesty, even if the answer is "I don’t know," she emphasized.

In the summit’s closing keynote address, Dr. J. Randall Curtis, director of the Harborview/University of Washington End-of-Life Care Research Program, Seattle, discussed how changing attitudes toward palliative are getting clinicians back in the mix.

"Palliative care is much more broadly accepted as an important part of health care" in both inpatient and outpatient settings, he said in an interview.

Palliative care applies to all patients who face a life-limiting illness or a chronic illness that may shorten life, whether they are actively dying or only starting to manage an illness or think about end-of-life care, he said.

"Hospital-based physicians in particular have a very important role in providing palliative care," said Dr. Curtis. They have the opportunity to introduce discussions of palliative care when patients are hospitalized for exacerbation of symptoms, or when they are hospitalized in the last stages of life, he noted.

"I think there is a growing realization that all physicians caring for patients with life-limiting or life-threatening illnesses need to have basic palliative care skills," although specialists can and should be called in for difficult cases, Dr. Curtis said.

Dr. Temel said she had no financial conflicts to disclose. Dr. Curtis has received funding from the National Institutes of Health and the National Institute of Nursing Research. The summit was sponsored in part by the Foundation for the National Institutes of Health and by Pfizer.

BETHESDA, MD. – Palliative care, once limited to the last days before death, is ripe for research and essential to improving patient quality of life, according to speakers at a summit sponsored by the National Institute of Nursing Research and National Institutes of Health partners.

"We have to put the clinician back in the mix," Dr. Ira R. Byock, professor of anesthesiology and director of palliative medicine at Dartmouth Medical School in Hanover, N.H., said in the opening keynote address.

According to several speakers at the meeting, putting the clinician back in the mix may mean changing the thinking about palliative care from something that begins in the last days of life to something started as early as a patient’s first day of a cancer diagnosis, as well as making it easier for clinicians to explore palliative care strategies.

One route to improving palliative care is through rigorous research in both inpatient and outpatient settings to see what works, according to Dr. Jennifer S. Temel, clinical director of thoracic oncology at Massachusetts General Hospital in Boston.

Dr. Temel made the case for the value of palliative care research when she discussed her recent study of early palliative care for patients with advanced lung cancer (N. Engl. J. Med. 2010;363:733-42).

Chemotherapy can improve symptoms, "but the problem is that patients are trading off their cancer symptoms for chemotherapy-related symptoms (fatigue, nausea, neuropathy), so overall physical quality of life is not significantly changed," she said.

In a randomized, controlled trial of 151 adults with metastatic non–small cell lung cancer, patients who received palliative care soon after their diagnoses had significantly less depression and anxiety, compared with controls. Another significant finding: The median survival was longer among patients in the early palliative care group, compared with controls (11.6 months vs. 8.9 months; P = .02).

Patients with advanced illnesses suffer from both physical and psychological symptoms, Dr. Temel said.

Dr. Temel’s findings suggest that early palliative care can be used in conjunction with chemotherapy, and cancer patients could be managed jointly in an oncology and clinic setting. However, more research is needed to support and expand her findings.

To help promote and enhance additional research in the field of palliative care, Dr. Amy P. Abernethy, an oncologist at Duke University Medical Center in Durham, N.C., described the creation of the U.S. Palliative Care Research Cooperative (PCRC) group. Dr. Abernethy is the coprincipal investigator of the PCRC, which was established in 2010 and funded by the National Institute of Nursing Research. The PCRC is currently establishing research protocols and procedures through which palliative care researchers will be able to suggest topics and submit grant applications, said Dr. Abernethy. "We must focus our scope, choose studies carefully, and do them well," she said.

The need to engage patients and caregivers as partners in palliative care research was addressed in many talks, as was the need for better communication among clinicians, patients, and caregivers about palliative care. Dianne Gray, a parent advocate whose young son died of a rare genetic disease, spoke about the importance of communication between doctors and patients facing end-of-life issues and reminded clinicians that families want to work with doctors. But families also want honesty, even if the answer is "I don’t know," she emphasized.

In the summit’s closing keynote address, Dr. J. Randall Curtis, director of the Harborview/University of Washington End-of-Life Care Research Program, Seattle, discussed how changing attitudes toward palliative are getting clinicians back in the mix.

"Palliative care is much more broadly accepted as an important part of health care" in both inpatient and outpatient settings, he said in an interview.

Palliative care applies to all patients who face a life-limiting illness or a chronic illness that may shorten life, whether they are actively dying or only starting to manage an illness or think about end-of-life care, he said.

"Hospital-based physicians in particular have a very important role in providing palliative care," said Dr. Curtis. They have the opportunity to introduce discussions of palliative care when patients are hospitalized for exacerbation of symptoms, or when they are hospitalized in the last stages of life, he noted.

"I think there is a growing realization that all physicians caring for patients with life-limiting or life-threatening illnesses need to have basic palliative care skills," although specialists can and should be called in for difficult cases, Dr. Curtis said.

Dr. Temel said she had no financial conflicts to disclose. Dr. Curtis has received funding from the National Institutes of Health and the National Institute of Nursing Research. The summit was sponsored in part by the Foundation for the National Institutes of Health and by Pfizer.