Patient & Survivor Care

SAN ANTONIO – Hypertension, dyslipidemia, and type 2 diabetes are common among breast cancer survivors – and so is nonadherence to medications prescribed for these major comorbid conditions.

That was the central finding from COMBO (Commonly Used Medications and Breast Cancer Outcomes), a retrospective cohort study of 4,216 breast cancer survivors belonging to Group Health Cooperative, Gregory S. Calip, Pharm.D., reported at the San Antonio Breast Cancer Symposium.

“This is the first study to investigate breast cancer characteristics and treatments in relation to nonadherence to chronic medications for hypertension, diabetes, and dyslipidemia,” said Dr. Calip of the University of Illinois, Chicago. “Our results suggest that some breast cancer treatments may be associated with nonadherence to antihypertensive agents and oral diabetes medications, but not statins. These findings highlight possible opportunities to improve comorbid condition care in the growing population of breast cancer survivors.”

The irony is that while experiencing breast cancer understandably renders survivors deeply concerned about the prospect of cancer-related death, by not taking their medications for these common comorbid conditions these women increase their overall mortality risk, and particularly their risk of death due to cardiovascular disease and stroke.

The women in the COMBO study had been diagnosed with stage I or II breast cancer during 1990-2008 and did not experience recurrence or a second primary breast cancer during their second year after breast cancer diagnosis. Their medication adherence during that second year was measured via automated health plan pharmacy dispensing records. Patients were classified as nonadherent if their medication possession ratio, or MPR, was less than 0.8.

Antihypertensive agents were prescribed for 1,929 of the subjects, statins for 1,072, and oral diabetes drugs for 449.

During days 366-730 post breast cancer diagnosis, 37% of the women were nonadherent to antihypertensive medications, 39% to prescribed statins, and 75% to their oral diabetes medications.

Common forms of breast cancer therapy were independently associated with increased likelihood of nonadherence in multivariate logistic regression analysis. For example, chemotherapy was associated with a 67% increased likelihood of nonadherence to diabetes medications during year 2 after breast cancer diagnosis. Patients who received radiation therapy or hormonal therapy were, respectively, 21% and 25% more likely to be nonadherent to antihypertensive therapy.

One factor associated with increased likelihood of adherence to medications for comorbid conditions was greater contact with a primary care physician. Breast cancer survivors who saw their primary care physicians two or more times during year 2 post diagnosis were 70% less likely to be nonadherent to antihypertensive therapy than were those who visited their primary care physicians less frequently.

Greater body mass index was associated with significantly less likelihood of nonadherence to antihypertensive agents but not statins or diabetes medications. When researchers used a BMI below 25 kg/m² for reference, patients with a BMI of 25-29.9 were 39% less likely to be nonadherent to antihypertensive therapy, those with a BMI of 30-34.9 kg/m² were 46% less likely, and women with a BMI of 35 kg/m² or greater were 63% less likely to be nonadherent to their antihypertensive therapy.

A higher Charlson comorbidity score of 2 or more during the first year following breast cancer diagnosis was associated with a 51% reduction in likelihood of nonadherence to diabetes medications during year 2 and a 46% lower nonadherence rate for statins than in patients with a Charlson score below 2.

As reported in previous studies of non-cancer patients, younger age was associated with increased nonadherence. This was true across the board for all three medication classes, although the age effect was most dramatic with respect to nonadherence to statins and oral diabetes medications. Fifty- to 54-year-olds were 3.4- and 1.8-fold more likely than were women age 65 or older to be nonadherent to diabetes drugs and statins, respectively, while breast cancer survivors under age 50 were 7.1- and 2.8-fold more likely to be nonadherent to those types of medications.

Discussant Dawn L. Hershman called the COMBO study medication nonadherence rates “pretty awful.” And if breast cancer survivors aren’t taking their medications for chronic comorbid conditions, it’s not much of a leap to think they may not be adherent to their breast cancer–related medications, she said. She urged her fellow breast cancer specialists to think beyond their specialty focus, consider the patient as a whole, and do what they can to promote adherence to medications targeting these potentially serious comorbidities.

“So, what can we do? We can try to engage technology,” said Dr. Hershman, a medical oncologist at Columbia University, New York.

She cited a randomized, controlled trial by other investigators which showed that automated phone calls reminding patients to take their cardiovascular medications had a salutary effect. In addition, she was an investigator in a large study of text messaging as an effective tool for improving adherence to hormonal therapy.

The COMBO study was supported by the National Cancer Institute and the University of Washington, Seattle. Dr. Calip reported having no financial conflicts.

[email protected]

SAN ANTONIO – Hypertension, dyslipidemia, and type 2 diabetes are common among breast cancer survivors – and so is nonadherence to medications prescribed for these major comorbid conditions.

That was the central finding from COMBO (Commonly Used Medications and Breast Cancer Outcomes), a retrospective cohort study of 4,216 breast cancer survivors belonging to Group Health Cooperative, Gregory S. Calip, Pharm.D., reported at the San Antonio Breast Cancer Symposium.

“This is the first study to investigate breast cancer characteristics and treatments in relation to nonadherence to chronic medications for hypertension, diabetes, and dyslipidemia,” said Dr. Calip of the University of Illinois, Chicago. “Our results suggest that some breast cancer treatments may be associated with nonadherence to antihypertensive agents and oral diabetes medications, but not statins. These findings highlight possible opportunities to improve comorbid condition care in the growing population of breast cancer survivors.”

The irony is that while experiencing breast cancer understandably renders survivors deeply concerned about the prospect of cancer-related death, by not taking their medications for these common comorbid conditions these women increase their overall mortality risk, and particularly their risk of death due to cardiovascular disease and stroke.

The women in the COMBO study had been diagnosed with stage I or II breast cancer during 1990-2008 and did not experience recurrence or a second primary breast cancer during their second year after breast cancer diagnosis. Their medication adherence during that second year was measured via automated health plan pharmacy dispensing records. Patients were classified as nonadherent if their medication possession ratio, or MPR, was less than 0.8.

Antihypertensive agents were prescribed for 1,929 of the subjects, statins for 1,072, and oral diabetes drugs for 449.

During days 366-730 post breast cancer diagnosis, 37% of the women were nonadherent to antihypertensive medications, 39% to prescribed statins, and 75% to their oral diabetes medications.

Common forms of breast cancer therapy were independently associated with increased likelihood of nonadherence in multivariate logistic regression analysis. For example, chemotherapy was associated with a 67% increased likelihood of nonadherence to diabetes medications during year 2 after breast cancer diagnosis. Patients who received radiation therapy or hormonal therapy were, respectively, 21% and 25% more likely to be nonadherent to antihypertensive therapy.

One factor associated with increased likelihood of adherence to medications for comorbid conditions was greater contact with a primary care physician. Breast cancer survivors who saw their primary care physicians two or more times during year 2 post diagnosis were 70% less likely to be nonadherent to antihypertensive therapy than were those who visited their primary care physicians less frequently.

Greater body mass index was associated with significantly less likelihood of nonadherence to antihypertensive agents but not statins or diabetes medications. When researchers used a BMI below 25 kg/m² for reference, patients with a BMI of 25-29.9 were 39% less likely to be nonadherent to antihypertensive therapy, those with a BMI of 30-34.9 kg/m² were 46% less likely, and women with a BMI of 35 kg/m² or greater were 63% less likely to be nonadherent to their antihypertensive therapy.

A higher Charlson comorbidity score of 2 or more during the first year following breast cancer diagnosis was associated with a 51% reduction in likelihood of nonadherence to diabetes medications during year 2 and a 46% lower nonadherence rate for statins than in patients with a Charlson score below 2.

As reported in previous studies of non-cancer patients, younger age was associated with increased nonadherence. This was true across the board for all three medication classes, although the age effect was most dramatic with respect to nonadherence to statins and oral diabetes medications. Fifty- to 54-year-olds were 3.4- and 1.8-fold more likely than were women age 65 or older to be nonadherent to diabetes drugs and statins, respectively, while breast cancer survivors under age 50 were 7.1- and 2.8-fold more likely to be nonadherent to those types of medications.

Discussant Dawn L. Hershman called the COMBO study medication nonadherence rates “pretty awful.” And if breast cancer survivors aren’t taking their medications for chronic comorbid conditions, it’s not much of a leap to think they may not be adherent to their breast cancer–related medications, she said. She urged her fellow breast cancer specialists to think beyond their specialty focus, consider the patient as a whole, and do what they can to promote adherence to medications targeting these potentially serious comorbidities.

“So, what can we do? We can try to engage technology,” said Dr. Hershman, a medical oncologist at Columbia University, New York.

She cited a randomized, controlled trial by other investigators which showed that automated phone calls reminding patients to take their cardiovascular medications had a salutary effect. In addition, she was an investigator in a large study of text messaging as an effective tool for improving adherence to hormonal therapy.

The COMBO study was supported by the National Cancer Institute and the University of Washington, Seattle. Dr. Calip reported having no financial conflicts.

[email protected]

SAN ANTONIO – Hypertension, dyslipidemia, and type 2 diabetes are common among breast cancer survivors – and so is nonadherence to medications prescribed for these major comorbid conditions.

That was the central finding from COMBO (Commonly Used Medications and Breast Cancer Outcomes), a retrospective cohort study of 4,216 breast cancer survivors belonging to Group Health Cooperative, Gregory S. Calip, Pharm.D., reported at the San Antonio Breast Cancer Symposium.

“This is the first study to investigate breast cancer characteristics and treatments in relation to nonadherence to chronic medications for hypertension, diabetes, and dyslipidemia,” said Dr. Calip of the University of Illinois, Chicago. “Our results suggest that some breast cancer treatments may be associated with nonadherence to antihypertensive agents and oral diabetes medications, but not statins. These findings highlight possible opportunities to improve comorbid condition care in the growing population of breast cancer survivors.”

The irony is that while experiencing breast cancer understandably renders survivors deeply concerned about the prospect of cancer-related death, by not taking their medications for these common comorbid conditions these women increase their overall mortality risk, and particularly their risk of death due to cardiovascular disease and stroke.

The women in the COMBO study had been diagnosed with stage I or II breast cancer during 1990-2008 and did not experience recurrence or a second primary breast cancer during their second year after breast cancer diagnosis. Their medication adherence during that second year was measured via automated health plan pharmacy dispensing records. Patients were classified as nonadherent if their medication possession ratio, or MPR, was less than 0.8.

Antihypertensive agents were prescribed for 1,929 of the subjects, statins for 1,072, and oral diabetes drugs for 449.

During days 366-730 post breast cancer diagnosis, 37% of the women were nonadherent to antihypertensive medications, 39% to prescribed statins, and 75% to their oral diabetes medications.

Common forms of breast cancer therapy were independently associated with increased likelihood of nonadherence in multivariate logistic regression analysis. For example, chemotherapy was associated with a 67% increased likelihood of nonadherence to diabetes medications during year 2 after breast cancer diagnosis. Patients who received radiation therapy or hormonal therapy were, respectively, 21% and 25% more likely to be nonadherent to antihypertensive therapy.

One factor associated with increased likelihood of adherence to medications for comorbid conditions was greater contact with a primary care physician. Breast cancer survivors who saw their primary care physicians two or more times during year 2 post diagnosis were 70% less likely to be nonadherent to antihypertensive therapy than were those who visited their primary care physicians less frequently.

Greater body mass index was associated with significantly less likelihood of nonadherence to antihypertensive agents but not statins or diabetes medications. When researchers used a BMI below 25 kg/m² for reference, patients with a BMI of 25-29.9 were 39% less likely to be nonadherent to antihypertensive therapy, those with a BMI of 30-34.9 kg/m² were 46% less likely, and women with a BMI of 35 kg/m² or greater were 63% less likely to be nonadherent to their antihypertensive therapy.

A higher Charlson comorbidity score of 2 or more during the first year following breast cancer diagnosis was associated with a 51% reduction in likelihood of nonadherence to diabetes medications during year 2 and a 46% lower nonadherence rate for statins than in patients with a Charlson score below 2.

As reported in previous studies of non-cancer patients, younger age was associated with increased nonadherence. This was true across the board for all three medication classes, although the age effect was most dramatic with respect to nonadherence to statins and oral diabetes medications. Fifty- to 54-year-olds were 3.4- and 1.8-fold more likely than were women age 65 or older to be nonadherent to diabetes drugs and statins, respectively, while breast cancer survivors under age 50 were 7.1- and 2.8-fold more likely to be nonadherent to those types of medications.

Discussant Dawn L. Hershman called the COMBO study medication nonadherence rates “pretty awful.” And if breast cancer survivors aren’t taking their medications for chronic comorbid conditions, it’s not much of a leap to think they may not be adherent to their breast cancer–related medications, she said. She urged her fellow breast cancer specialists to think beyond their specialty focus, consider the patient as a whole, and do what they can to promote adherence to medications targeting these potentially serious comorbidities.

“So, what can we do? We can try to engage technology,” said Dr. Hershman, a medical oncologist at Columbia University, New York.

She cited a randomized, controlled trial by other investigators which showed that automated phone calls reminding patients to take their cardiovascular medications had a salutary effect. In addition, she was an investigator in a large study of text messaging as an effective tool for improving adherence to hormonal therapy.

The COMBO study was supported by the National Cancer Institute and the University of Washington, Seattle. Dr. Calip reported having no financial conflicts.

[email protected]

SAN ANTONIO – Low-level laser therapy proved highly effective in managing chemotherapy-induced oral mucositis in a retrospective study.

Although this was the first study of low-level laser therapy in breast cancer patients, this form of therapy is already widely used to prevent and treat oral mucositis in hematopoietic stem cell transplant recipients as well as in patients with head and neck cancer. These preliminary findings in a breast cancer population warrant confirmation in a randomized controlled trial, Sandrine Censabella, Ph.D., said at the San Antonio Breast Cancer Symposium.

Roughly 40% of patients develop oral mucositis as a consequence of standard-dose chemotherapy. Oral mucositis is the most debilitating, severe, and costly nonhematologic complication of oncologic therapy. It compromises both quality of life and treatment outcomes, said Dr. Censabella of Jessa Hospital in Hasselt, Belgium.

She reported on 93 patients with stage 0-IV breast cancer and chemotherapy-induced oral mucositis who received low-level laser therapy using a gallium arsenide laser at 665-nm wavelength and 100 mW of output power combined with a continuous-emission infrared laser with an output power of 500 mW. The laser energy, 4 J per application point, was delivered via a 600-mcm optical fiber.

The treatment schedule was two sessions per week until lesion healing occurred. Depending on the extent of the oral mucositis, up to seven oral sites could be treated: lips, tongue, palate, inside of the two cheeks, tonsils, and mouth floor.

Outcomes were assessed in a standardized fashion by trained nurses using the World Health Organization 0-4 grading scale, where 0 means unaffected, 1 represents soreness and erythema, 2 means erythema and ulcers but with an ability to eat solid foods, 3 is for patients with ulcers who require a liquid diet only, and 4 is for patients incapable of oral nutritional intake. In addition, investigators calculated an oral mucositis score for every patient by adding up the WHO grades at all affected sites.

Laser therapy began a mean of 49 days after the start of chemotherapy, which was anthracycline based in two-thirds of cases. The mean age of the women was 54.8 years.

Subjects received a mean of 5.7 laser treatment sessions, during which they showed a significant reduction in oral mucositis severity. At baseline, 60% of patients had WHO grade 2 lesions, a rate that dropped to 30% at the end of treatment several weeks later. While only 12% of patients were WHO grade 1 at baseline, 65% were at the conclusion of the laser treatment program. Twenty-eight percent of women were WHO grade 3 at entry, compared with just 5.4% after laser treatment.

The mean baseline combined oral mucositis score averaged 6.6, improving to 2.78 at treatment’s end.

Self-reported pain scores improved from 5.14 at baseline on a 10-point scale to 1.64 at the conclusion of laser therapy.

At the end of laser therapy, only 2% had a worse WHO grade than at baseline, 8.6% had a worse composite oral mucositis score, and no one reported more pain than at entry.

“These findings are the first to document a beneficial effect of low-level laser therapy in a large group of breast cancer patients and suggest that low-level laser therapy might become a standard management for oral mucositis in all cancer patients,” Dr. Censabella said.

She reported having no financial conflicts regarding this study.

[email protected]

SAN ANTONIO – Low-level laser therapy proved highly effective in managing chemotherapy-induced oral mucositis in a retrospective study.

Although this was the first study of low-level laser therapy in breast cancer patients, this form of therapy is already widely used to prevent and treat oral mucositis in hematopoietic stem cell transplant recipients as well as in patients with head and neck cancer. These preliminary findings in a breast cancer population warrant confirmation in a randomized controlled trial, Sandrine Censabella, Ph.D., said at the San Antonio Breast Cancer Symposium.

Roughly 40% of patients develop oral mucositis as a consequence of standard-dose chemotherapy. Oral mucositis is the most debilitating, severe, and costly nonhematologic complication of oncologic therapy. It compromises both quality of life and treatment outcomes, said Dr. Censabella of Jessa Hospital in Hasselt, Belgium.

She reported on 93 patients with stage 0-IV breast cancer and chemotherapy-induced oral mucositis who received low-level laser therapy using a gallium arsenide laser at 665-nm wavelength and 100 mW of output power combined with a continuous-emission infrared laser with an output power of 500 mW. The laser energy, 4 J per application point, was delivered via a 600-mcm optical fiber.

The treatment schedule was two sessions per week until lesion healing occurred. Depending on the extent of the oral mucositis, up to seven oral sites could be treated: lips, tongue, palate, inside of the two cheeks, tonsils, and mouth floor.

Outcomes were assessed in a standardized fashion by trained nurses using the World Health Organization 0-4 grading scale, where 0 means unaffected, 1 represents soreness and erythema, 2 means erythema and ulcers but with an ability to eat solid foods, 3 is for patients with ulcers who require a liquid diet only, and 4 is for patients incapable of oral nutritional intake. In addition, investigators calculated an oral mucositis score for every patient by adding up the WHO grades at all affected sites.

Laser therapy began a mean of 49 days after the start of chemotherapy, which was anthracycline based in two-thirds of cases. The mean age of the women was 54.8 years.

Subjects received a mean of 5.7 laser treatment sessions, during which they showed a significant reduction in oral mucositis severity. At baseline, 60% of patients had WHO grade 2 lesions, a rate that dropped to 30% at the end of treatment several weeks later. While only 12% of patients were WHO grade 1 at baseline, 65% were at the conclusion of the laser treatment program. Twenty-eight percent of women were WHO grade 3 at entry, compared with just 5.4% after laser treatment.

The mean baseline combined oral mucositis score averaged 6.6, improving to 2.78 at treatment’s end.

Self-reported pain scores improved from 5.14 at baseline on a 10-point scale to 1.64 at the conclusion of laser therapy.

At the end of laser therapy, only 2% had a worse WHO grade than at baseline, 8.6% had a worse composite oral mucositis score, and no one reported more pain than at entry.

“These findings are the first to document a beneficial effect of low-level laser therapy in a large group of breast cancer patients and suggest that low-level laser therapy might become a standard management for oral mucositis in all cancer patients,” Dr. Censabella said.

She reported having no financial conflicts regarding this study.

[email protected]

SAN ANTONIO – Low-level laser therapy proved highly effective in managing chemotherapy-induced oral mucositis in a retrospective study.

Although this was the first study of low-level laser therapy in breast cancer patients, this form of therapy is already widely used to prevent and treat oral mucositis in hematopoietic stem cell transplant recipients as well as in patients with head and neck cancer. These preliminary findings in a breast cancer population warrant confirmation in a randomized controlled trial, Sandrine Censabella, Ph.D., said at the San Antonio Breast Cancer Symposium.

Roughly 40% of patients develop oral mucositis as a consequence of standard-dose chemotherapy. Oral mucositis is the most debilitating, severe, and costly nonhematologic complication of oncologic therapy. It compromises both quality of life and treatment outcomes, said Dr. Censabella of Jessa Hospital in Hasselt, Belgium.

She reported on 93 patients with stage 0-IV breast cancer and chemotherapy-induced oral mucositis who received low-level laser therapy using a gallium arsenide laser at 665-nm wavelength and 100 mW of output power combined with a continuous-emission infrared laser with an output power of 500 mW. The laser energy, 4 J per application point, was delivered via a 600-mcm optical fiber.

The treatment schedule was two sessions per week until lesion healing occurred. Depending on the extent of the oral mucositis, up to seven oral sites could be treated: lips, tongue, palate, inside of the two cheeks, tonsils, and mouth floor.

Outcomes were assessed in a standardized fashion by trained nurses using the World Health Organization 0-4 grading scale, where 0 means unaffected, 1 represents soreness and erythema, 2 means erythema and ulcers but with an ability to eat solid foods, 3 is for patients with ulcers who require a liquid diet only, and 4 is for patients incapable of oral nutritional intake. In addition, investigators calculated an oral mucositis score for every patient by adding up the WHO grades at all affected sites.

Laser therapy began a mean of 49 days after the start of chemotherapy, which was anthracycline based in two-thirds of cases. The mean age of the women was 54.8 years.

Subjects received a mean of 5.7 laser treatment sessions, during which they showed a significant reduction in oral mucositis severity. At baseline, 60% of patients had WHO grade 2 lesions, a rate that dropped to 30% at the end of treatment several weeks later. While only 12% of patients were WHO grade 1 at baseline, 65% were at the conclusion of the laser treatment program. Twenty-eight percent of women were WHO grade 3 at entry, compared with just 5.4% after laser treatment.

The mean baseline combined oral mucositis score averaged 6.6, improving to 2.78 at treatment’s end.

Self-reported pain scores improved from 5.14 at baseline on a 10-point scale to 1.64 at the conclusion of laser therapy.

At the end of laser therapy, only 2% had a worse WHO grade than at baseline, 8.6% had a worse composite oral mucositis score, and no one reported more pain than at entry.

“These findings are the first to document a beneficial effect of low-level laser therapy in a large group of breast cancer patients and suggest that low-level laser therapy might become a standard management for oral mucositis in all cancer patients,” Dr. Censabella said.

She reported having no financial conflicts regarding this study.

[email protected]

The extent of pain, depression, and anorexia are rising in the last year of life for oncology patients, based on a survey of their family members.

Moderate or severe pain was experienced for at least a month by over 57% of 7,204 patients in their last year of life, and the incidence of pain appears to have increased between 1998 and 2010, based on data from participants who died during the longitudinal, community-based Health and Retirement study. Patients’ family members also reported that over 51% of patients experienced depression and 64% experienced anorexia in their last year of life.

The data reflect increases in the incidence of moderate to severe pain from nearly 47% in 1998-2000 to nearly 55% in 2008-2010. Increases also were noted in reports of depression and periodic confusion, researchers reported in the Feb. 2 online edition of Annals of Internal Medicine [doi:10.7326/M13-1609]). .

The researchers note other studies indicate that the intensity of treatment and the rate of adverse transitions have been increasing near the end of life. While hospice care is on the rise, it is often “tacked on” to this more intense late-life care; the median hospice stay is less than 3 weeks and such patients may not achieve symptomatic relief. Patients may not have consistent access to palliative services in outpatient, home, and long-term facility settings where most of the course of a terminal illness takes place, wrote Adam E. Singer of the Pardee RAND Graduate School, Santa Monica, Calif., and his colleagues.

The study was supported by the National Institute of Nursing Research and the Medical Scientist Training Program at the University of California.

The extent of pain, depression, and anorexia are rising in the last year of life for oncology patients, based on a survey of their family members.

Moderate or severe pain was experienced for at least a month by over 57% of 7,204 patients in their last year of life, and the incidence of pain appears to have increased between 1998 and 2010, based on data from participants who died during the longitudinal, community-based Health and Retirement study. Patients’ family members also reported that over 51% of patients experienced depression and 64% experienced anorexia in their last year of life.

The data reflect increases in the incidence of moderate to severe pain from nearly 47% in 1998-2000 to nearly 55% in 2008-2010. Increases also were noted in reports of depression and periodic confusion, researchers reported in the Feb. 2 online edition of Annals of Internal Medicine [doi:10.7326/M13-1609]). .

The researchers note other studies indicate that the intensity of treatment and the rate of adverse transitions have been increasing near the end of life. While hospice care is on the rise, it is often “tacked on” to this more intense late-life care; the median hospice stay is less than 3 weeks and such patients may not achieve symptomatic relief. Patients may not have consistent access to palliative services in outpatient, home, and long-term facility settings where most of the course of a terminal illness takes place, wrote Adam E. Singer of the Pardee RAND Graduate School, Santa Monica, Calif., and his colleagues.

The study was supported by the National Institute of Nursing Research and the Medical Scientist Training Program at the University of California.

The extent of pain, depression, and anorexia are rising in the last year of life for oncology patients, based on a survey of their family members.

Moderate or severe pain was experienced for at least a month by over 57% of 7,204 patients in their last year of life, and the incidence of pain appears to have increased between 1998 and 2010, based on data from participants who died during the longitudinal, community-based Health and Retirement study. Patients’ family members also reported that over 51% of patients experienced depression and 64% experienced anorexia in their last year of life.

The data reflect increases in the incidence of moderate to severe pain from nearly 47% in 1998-2000 to nearly 55% in 2008-2010. Increases also were noted in reports of depression and periodic confusion, researchers reported in the Feb. 2 online edition of Annals of Internal Medicine [doi:10.7326/M13-1609]). .

The researchers note other studies indicate that the intensity of treatment and the rate of adverse transitions have been increasing near the end of life. While hospice care is on the rise, it is often “tacked on” to this more intense late-life care; the median hospice stay is less than 3 weeks and such patients may not achieve symptomatic relief. Patients may not have consistent access to palliative services in outpatient, home, and long-term facility settings where most of the course of a terminal illness takes place, wrote Adam E. Singer of the Pardee RAND Graduate School, Santa Monica, Calif., and his colleagues.

The study was supported by the National Institute of Nursing Research and the Medical Scientist Training Program at the University of California.

A new formulation of extended-release hydrocodone with abuse-deterrent properties has been approved by the Food and Drug Administration, the manufacturer, Zogenix, has announced.

The new formulation, marketed as Zohydro ER, contains extended-release hydrocodone with “pharmaceutical excipients that immediately form a viscous gel when crushed and dissolved in liquids or solvents,” according to the Jan. 30 statement released by the company. The technology is called “BeadTek.”

The company expects to start transitioning from the currently available Zohydro ER product to the newly formulated product in the second quarter of 2015 for all the prescribed strengths of Zohydro ER, to avoid disrupting patients who are being treated with the product, the statement said.

Zohydro ER is an opioid agonist approved for the management of pain “severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate,” according to the prescribing information.

In the second half of this year, the company plans to submit the results of ongoing Human Abuse Liability studies, “which will further characterize the abuse-deterrent properties of the new formulation” and will support the addition of abuse-deterrent claims to the prescribing information, the company statement said. The statement refers to the FDA’s draft guidance for the evaluation and labeling of abuse-deterrent opioids, which describes the abuse-deterrent claims.

Zohydro ER was approved by the FDA in 2013.

[email protected]

A new formulation of extended-release hydrocodone with abuse-deterrent properties has been approved by the Food and Drug Administration, the manufacturer, Zogenix, has announced.

The new formulation, marketed as Zohydro ER, contains extended-release hydrocodone with “pharmaceutical excipients that immediately form a viscous gel when crushed and dissolved in liquids or solvents,” according to the Jan. 30 statement released by the company. The technology is called “BeadTek.”

The company expects to start transitioning from the currently available Zohydro ER product to the newly formulated product in the second quarter of 2015 for all the prescribed strengths of Zohydro ER, to avoid disrupting patients who are being treated with the product, the statement said.

Zohydro ER is an opioid agonist approved for the management of pain “severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate,” according to the prescribing information.

In the second half of this year, the company plans to submit the results of ongoing Human Abuse Liability studies, “which will further characterize the abuse-deterrent properties of the new formulation” and will support the addition of abuse-deterrent claims to the prescribing information, the company statement said. The statement refers to the FDA’s draft guidance for the evaluation and labeling of abuse-deterrent opioids, which describes the abuse-deterrent claims.

Zohydro ER was approved by the FDA in 2013.

[email protected]

A new formulation of extended-release hydrocodone with abuse-deterrent properties has been approved by the Food and Drug Administration, the manufacturer, Zogenix, has announced.

The new formulation, marketed as Zohydro ER, contains extended-release hydrocodone with “pharmaceutical excipients that immediately form a viscous gel when crushed and dissolved in liquids or solvents,” according to the Jan. 30 statement released by the company. The technology is called “BeadTek.”

The company expects to start transitioning from the currently available Zohydro ER product to the newly formulated product in the second quarter of 2015 for all the prescribed strengths of Zohydro ER, to avoid disrupting patients who are being treated with the product, the statement said.

Zohydro ER is an opioid agonist approved for the management of pain “severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate,” according to the prescribing information.

In the second half of this year, the company plans to submit the results of ongoing Human Abuse Liability studies, “which will further characterize the abuse-deterrent properties of the new formulation” and will support the addition of abuse-deterrent claims to the prescribing information, the company statement said. The statement refers to the FDA’s draft guidance for the evaluation and labeling of abuse-deterrent opioids, which describes the abuse-deterrent claims.

Zohydro ER was approved by the FDA in 2013.

[email protected]

SAN ANTONIO – Breast cancer patients are often advised that in order to avoid developing lymphedema they should shun blood pressure cuffs, injections, and blood draws on their at-risk arm as well as airplane travel unless wearing a compression sleeve.

All these recommendations are anecdotally based. None withstood formal evaluation in a prospective study of 710 breast cancer patients with 860 treated and thus potentially at-risk breasts, Chantal M. Ferguson reported at the San Antonio Breast Cancer Symposium.

“Our findings don’t support current guidelines regarding these activities and suggest that further studies are needed to determine if these guidelines are appropriate,” said Ms. Ferguson of Massachusetts General Hospital, Boston.

Standard practice for newly diagnosed breast cancer patients at Mass. General is to enter into a prospective screening program for lymphedema, a chronic, painful swelling caused by damage to the lymphatic system secondary to breast cancer therapy.

Breast cancer patients routinely have bilateral arm volume measurements taken using a perometer preoperatively, postoperatively, after finishing chemotherapy and radiotherapy, and at 3- to 7-month intervals thereafter following completion of treatment. At each measurement, data are collected on exposures to airplane flights, blood pressure readings, and the other often-cited putative risk factors.

The incidence of lymphedema among the 710 patients in the study at 24 months was 7.05%. The diagnosis required at least a 10% increase in arm volume, compared with the untreated side. For women who underwent bilateral breast surgery, a weight-adjusted volume change formula was employed.

Consistent with the medical literature, axial lymph node dissection and a higher preoperative body mass index were significantly associated with the development of lymphedema. So was self-reported trauma to the at-risk arm, although the reported trauma ranged in severity from bruises to fractures in motor vehicle accidents.

Session cochair Dr. Michelle E. Melisko observed that few medical oncologists are well informed about lymphedema or the numerous and highly complex functions of the lymphatic system, so she was favorably impressed that physicians at Mass. General have incorporated structured screening for the disorder as part of the institutional standard of care.

She cautioned, however, that rates of the risk factor events under study were relatively low. For example, only 17% of the breast cancer patients had one or more blood pressure measurements taken on their at-risk arm during 2 years of prospective follow-up, 9% had one or more blood draws, and 15% of patients flew for a total of 12 hours or more.

“I’m not sure that we can take these data to say we can let patients go hog wild and get their blood pressure measured all the time on that arm. This is a large prospective trial featuring a broad range of patient ages and BMIs, and both lumpectomy and mastectomy patients, and the trial adds a lot to the literature, but it does need to be interpreted with caution,” said Dr. Melisko of the University of California, San Francisco.

The study was funded by the National Cancer Institute and the Adele McKinnon Research Fund for Breast Cancer–related Lymphedema. Ms. Ferguson reported having no financial conflicts.

[email protected]

SAN ANTONIO – Breast cancer patients are often advised that in order to avoid developing lymphedema they should shun blood pressure cuffs, injections, and blood draws on their at-risk arm as well as airplane travel unless wearing a compression sleeve.

All these recommendations are anecdotally based. None withstood formal evaluation in a prospective study of 710 breast cancer patients with 860 treated and thus potentially at-risk breasts, Chantal M. Ferguson reported at the San Antonio Breast Cancer Symposium.

“Our findings don’t support current guidelines regarding these activities and suggest that further studies are needed to determine if these guidelines are appropriate,” said Ms. Ferguson of Massachusetts General Hospital, Boston.

Standard practice for newly diagnosed breast cancer patients at Mass. General is to enter into a prospective screening program for lymphedema, a chronic, painful swelling caused by damage to the lymphatic system secondary to breast cancer therapy.

Breast cancer patients routinely have bilateral arm volume measurements taken using a perometer preoperatively, postoperatively, after finishing chemotherapy and radiotherapy, and at 3- to 7-month intervals thereafter following completion of treatment. At each measurement, data are collected on exposures to airplane flights, blood pressure readings, and the other often-cited putative risk factors.

The incidence of lymphedema among the 710 patients in the study at 24 months was 7.05%. The diagnosis required at least a 10% increase in arm volume, compared with the untreated side. For women who underwent bilateral breast surgery, a weight-adjusted volume change formula was employed.

Consistent with the medical literature, axial lymph node dissection and a higher preoperative body mass index were significantly associated with the development of lymphedema. So was self-reported trauma to the at-risk arm, although the reported trauma ranged in severity from bruises to fractures in motor vehicle accidents.

Session cochair Dr. Michelle E. Melisko observed that few medical oncologists are well informed about lymphedema or the numerous and highly complex functions of the lymphatic system, so she was favorably impressed that physicians at Mass. General have incorporated structured screening for the disorder as part of the institutional standard of care.

She cautioned, however, that rates of the risk factor events under study were relatively low. For example, only 17% of the breast cancer patients had one or more blood pressure measurements taken on their at-risk arm during 2 years of prospective follow-up, 9% had one or more blood draws, and 15% of patients flew for a total of 12 hours or more.

“I’m not sure that we can take these data to say we can let patients go hog wild and get their blood pressure measured all the time on that arm. This is a large prospective trial featuring a broad range of patient ages and BMIs, and both lumpectomy and mastectomy patients, and the trial adds a lot to the literature, but it does need to be interpreted with caution,” said Dr. Melisko of the University of California, San Francisco.

The study was funded by the National Cancer Institute and the Adele McKinnon Research Fund for Breast Cancer–related Lymphedema. Ms. Ferguson reported having no financial conflicts.

[email protected]

SAN ANTONIO – Breast cancer patients are often advised that in order to avoid developing lymphedema they should shun blood pressure cuffs, injections, and blood draws on their at-risk arm as well as airplane travel unless wearing a compression sleeve.

All these recommendations are anecdotally based. None withstood formal evaluation in a prospective study of 710 breast cancer patients with 860 treated and thus potentially at-risk breasts, Chantal M. Ferguson reported at the San Antonio Breast Cancer Symposium.

“Our findings don’t support current guidelines regarding these activities and suggest that further studies are needed to determine if these guidelines are appropriate,” said Ms. Ferguson of Massachusetts General Hospital, Boston.

Standard practice for newly diagnosed breast cancer patients at Mass. General is to enter into a prospective screening program for lymphedema, a chronic, painful swelling caused by damage to the lymphatic system secondary to breast cancer therapy.

Breast cancer patients routinely have bilateral arm volume measurements taken using a perometer preoperatively, postoperatively, after finishing chemotherapy and radiotherapy, and at 3- to 7-month intervals thereafter following completion of treatment. At each measurement, data are collected on exposures to airplane flights, blood pressure readings, and the other often-cited putative risk factors.

The incidence of lymphedema among the 710 patients in the study at 24 months was 7.05%. The diagnosis required at least a 10% increase in arm volume, compared with the untreated side. For women who underwent bilateral breast surgery, a weight-adjusted volume change formula was employed.

Consistent with the medical literature, axial lymph node dissection and a higher preoperative body mass index were significantly associated with the development of lymphedema. So was self-reported trauma to the at-risk arm, although the reported trauma ranged in severity from bruises to fractures in motor vehicle accidents.

Session cochair Dr. Michelle E. Melisko observed that few medical oncologists are well informed about lymphedema or the numerous and highly complex functions of the lymphatic system, so she was favorably impressed that physicians at Mass. General have incorporated structured screening for the disorder as part of the institutional standard of care.

She cautioned, however, that rates of the risk factor events under study were relatively low. For example, only 17% of the breast cancer patients had one or more blood pressure measurements taken on their at-risk arm during 2 years of prospective follow-up, 9% had one or more blood draws, and 15% of patients flew for a total of 12 hours or more.

“I’m not sure that we can take these data to say we can let patients go hog wild and get their blood pressure measured all the time on that arm. This is a large prospective trial featuring a broad range of patient ages and BMIs, and both lumpectomy and mastectomy patients, and the trial adds a lot to the literature, but it does need to be interpreted with caution,” said Dr. Melisko of the University of California, San Francisco.

The study was funded by the National Cancer Institute and the Adele McKinnon Research Fund for Breast Cancer–related Lymphedema. Ms. Ferguson reported having no financial conflicts.

[email protected]

SILVER SPRING, MD. – A novel treatment for invasive aspergillosis and invasive mucormycosis gained the support of a Food and Drug Administration advisory panel, although members were more ambivalent about the mucormycosis indication, based on the small amount of data available in those patients.

At a meeting on Jan. 22, the FDA’s Anti-Infective Drugs Advisory Committee voted 11-0 that there was “substantial evidence” that isavuconazonium, an antifungal prodrug, was safe and effective for the treatment of invasive aspergillosis, a life-threatening condition most commonly seen in immunocompromised patients. The drug was studied in a phase III study comparing isavuconazonium to voriconazole, the standard of care, in more than 500 patients.

The panel voted 8-2, with one abstention, that there was substantial evidence it was safe and effective for treating patients with invasive mucormycosis, with panelists voting on both sides of the question citing the study of only 37 patients that used historical controls as an issue. Those supporting approval for mucormycosis said that, if approved, the manufacturer, Astellas, should be required to conduct a phase IV trial further evaluating this treatment for patients with this infection.

Isavuconazonium is a prodrug of isavuconazole, a triazole antifungal, and would be available in an oral capsule formulation and a powder formulation that is reconstituted for intravenous administration (and needs to be administered through an in-line filter in case of particulate formation).

For aspergillosis, “I do believe that this drug provides a reasonable alternative to the current therapies that are available without additional toxicities,” said panelist Dr. Paige Waterman of the Global Emerging Infections Surveillance and Response System at the Walter Reed Army Medical Center, Silver Spring, Md. Other panelists agreed with her recommendations that labeling should make clear that it should not be used in people under age 18 years or in pregnant women, that a filter should be used when administered intravenously, and that labeling should include a statement about the increased risk of hepatotoxicity that also appears in the labeling of other drugs in the same class.

Because it has been associated with a shortened QT interval, she said that screening ECGs should be recommended for patients and that there should be some extra caution when it is prescribed to people who are Asian or of Asian descent, since drug concentrations were slightly higher among Asian patients who received the drug. Other recommendations from panelists included the need to conduct studies of the drug to provide information on therapeutic drug monitoring and in people under 18 years.

For treatment of invasive mucormycosis, an even rarer fungal infection which, in hospitals, is associated with the use of contaminated materials or organ transplantation, the panelists were more hesitant, but those voting in favor of approval cited the significance of the condition and the reasonable efficacy results in the study, stressing that postmarketing studies were critical. Panelists also noted that more clinical data are clearly needed in patients with this infection and the lack of data directly comparing it to amphotericin B – the only FDA-approved drug for this indication – was problematic.

Elizabeth Mechcatie/Frontline Medical News

“This drug really does fill an unmet need; I have high hopes that it is at least as good as amphotericin. But I do think we need more data to confirm that,” said Dr. Michael Neely, chair of antimicrobial stewardship at Children’s Hospital, Los Angeles, who was among those voting in favor of this indication. It appears to have a better safety profile and it would be available in both oral and intravenous formulations, he added. Amphotericin B is available only in an intravenous (IV) formulation.

If approved, isavuconazonium would provide an alternative to voriconazole for treating aspergillosis, and the IV formulation does not contain cyclodextrin, unlike the IV formulation of voriconazole, which limits its use in patients with moderate to severe renal dysfunction, according to Astellas. Safety concerns specific to isavuconazonium include QT-segment shortening and particulate formation in the IV formulation, according to the FDA.

The randomized, double-blind, international, noninferiority study compared treatment with isavuconazonium to voriconazole in 516 adults with invasive aspergillosis. In the randomized study, the mean age of patients was 51 years, 60% were men, most were white, 11% were in the United States and Canada, 20% had had an allogeneic bone marrow transplant, and 70% had an uncontrolled malignancy at baseline (Infect. Drug Resist. 2013;6:16374). The primary effectiveness endpoint, all-cause mortality through day 42, was 19% in those on isavuconazonium, compared with 20% in those on voriconazole. The study met the prespecified noninferiority margin. The rates of deaths and serious adverse events were similar to voriconazole, and there were fewer adverse events in those on isavuconazonium requiring discontinuation of the drug (14% vs. 23%).

Differences in adverse events included lower rates of hepatobiliary disorders, including hyperbilirubinemia, abnormal hepatic function, and jaundice (9% vs. 16%); skin and subcutaneous tissue disorders, including rash, erythema, and drug eruption (34% vs 43%) associated with isavuconazonium, compared with voriconazole. Common adverse events included nausea (28%), vomiting (25%), and diarrhea (24%). Decreases in the QT segment occurred in 7.5% of those on isavuconazonium, compared with 4.5% of those on voriconazole, but were not associated with clinical events.

The prospective, open-label, single-arm study evaluated isavuconazonium in 37 patients with proven or probable mucormycosis infections, whose mean age was 49 years; 59% had a hematologic malignancy, and about 40% were neutropenic at baseline. All-cause mortality at day 42 was almost 38%, which was similar to the mortality rate for amphotericin in the literature, according to Astellas.

There are about 12,000 cases of aspergillosis and about 500 cases of mucormycosis in the United States every year, the company said. In addition to voriconazole, other drugs approved for invasive aspergillosis include amphotericin formulations, itraconazole, and caspofungin. The FDA usually follows the recommendations of its advisory panels. The FDA is expected to make a decision by March 8, according to Astellas, which plans to market the drug as Cresemba if approved. It is also under review in Europe for the same indications.

Panelists were cleared of potential conflicts of interest related to the topic of the meeting. In some cases, a panelist may be given a waiver but not at this meeting.

[email protected]

SILVER SPRING, MD. – A novel treatment for invasive aspergillosis and invasive mucormycosis gained the support of a Food and Drug Administration advisory panel, although members were more ambivalent about the mucormycosis indication, based on the small amount of data available in those patients.

At a meeting on Jan. 22, the FDA’s Anti-Infective Drugs Advisory Committee voted 11-0 that there was “substantial evidence” that isavuconazonium, an antifungal prodrug, was safe and effective for the treatment of invasive aspergillosis, a life-threatening condition most commonly seen in immunocompromised patients. The drug was studied in a phase III study comparing isavuconazonium to voriconazole, the standard of care, in more than 500 patients.

The panel voted 8-2, with one abstention, that there was substantial evidence it was safe and effective for treating patients with invasive mucormycosis, with panelists voting on both sides of the question citing the study of only 37 patients that used historical controls as an issue. Those supporting approval for mucormycosis said that, if approved, the manufacturer, Astellas, should be required to conduct a phase IV trial further evaluating this treatment for patients with this infection.

Isavuconazonium is a prodrug of isavuconazole, a triazole antifungal, and would be available in an oral capsule formulation and a powder formulation that is reconstituted for intravenous administration (and needs to be administered through an in-line filter in case of particulate formation).

For aspergillosis, “I do believe that this drug provides a reasonable alternative to the current therapies that are available without additional toxicities,” said panelist Dr. Paige Waterman of the Global Emerging Infections Surveillance and Response System at the Walter Reed Army Medical Center, Silver Spring, Md. Other panelists agreed with her recommendations that labeling should make clear that it should not be used in people under age 18 years or in pregnant women, that a filter should be used when administered intravenously, and that labeling should include a statement about the increased risk of hepatotoxicity that also appears in the labeling of other drugs in the same class.

Because it has been associated with a shortened QT interval, she said that screening ECGs should be recommended for patients and that there should be some extra caution when it is prescribed to people who are Asian or of Asian descent, since drug concentrations were slightly higher among Asian patients who received the drug. Other recommendations from panelists included the need to conduct studies of the drug to provide information on therapeutic drug monitoring and in people under 18 years.

For treatment of invasive mucormycosis, an even rarer fungal infection which, in hospitals, is associated with the use of contaminated materials or organ transplantation, the panelists were more hesitant, but those voting in favor of approval cited the significance of the condition and the reasonable efficacy results in the study, stressing that postmarketing studies were critical. Panelists also noted that more clinical data are clearly needed in patients with this infection and the lack of data directly comparing it to amphotericin B – the only FDA-approved drug for this indication – was problematic.

Elizabeth Mechcatie/Frontline Medical News

“This drug really does fill an unmet need; I have high hopes that it is at least as good as amphotericin. But I do think we need more data to confirm that,” said Dr. Michael Neely, chair of antimicrobial stewardship at Children’s Hospital, Los Angeles, who was among those voting in favor of this indication. It appears to have a better safety profile and it would be available in both oral and intravenous formulations, he added. Amphotericin B is available only in an intravenous (IV) formulation.

If approved, isavuconazonium would provide an alternative to voriconazole for treating aspergillosis, and the IV formulation does not contain cyclodextrin, unlike the IV formulation of voriconazole, which limits its use in patients with moderate to severe renal dysfunction, according to Astellas. Safety concerns specific to isavuconazonium include QT-segment shortening and particulate formation in the IV formulation, according to the FDA.

The randomized, double-blind, international, noninferiority study compared treatment with isavuconazonium to voriconazole in 516 adults with invasive aspergillosis. In the randomized study, the mean age of patients was 51 years, 60% were men, most were white, 11% were in the United States and Canada, 20% had had an allogeneic bone marrow transplant, and 70% had an uncontrolled malignancy at baseline (Infect. Drug Resist. 2013;6:16374). The primary effectiveness endpoint, all-cause mortality through day 42, was 19% in those on isavuconazonium, compared with 20% in those on voriconazole. The study met the prespecified noninferiority margin. The rates of deaths and serious adverse events were similar to voriconazole, and there were fewer adverse events in those on isavuconazonium requiring discontinuation of the drug (14% vs. 23%).

Differences in adverse events included lower rates of hepatobiliary disorders, including hyperbilirubinemia, abnormal hepatic function, and jaundice (9% vs. 16%); skin and subcutaneous tissue disorders, including rash, erythema, and drug eruption (34% vs 43%) associated with isavuconazonium, compared with voriconazole. Common adverse events included nausea (28%), vomiting (25%), and diarrhea (24%). Decreases in the QT segment occurred in 7.5% of those on isavuconazonium, compared with 4.5% of those on voriconazole, but were not associated with clinical events.

The prospective, open-label, single-arm study evaluated isavuconazonium in 37 patients with proven or probable mucormycosis infections, whose mean age was 49 years; 59% had a hematologic malignancy, and about 40% were neutropenic at baseline. All-cause mortality at day 42 was almost 38%, which was similar to the mortality rate for amphotericin in the literature, according to Astellas.

There are about 12,000 cases of aspergillosis and about 500 cases of mucormycosis in the United States every year, the company said. In addition to voriconazole, other drugs approved for invasive aspergillosis include amphotericin formulations, itraconazole, and caspofungin. The FDA usually follows the recommendations of its advisory panels. The FDA is expected to make a decision by March 8, according to Astellas, which plans to market the drug as Cresemba if approved. It is also under review in Europe for the same indications.

Panelists were cleared of potential conflicts of interest related to the topic of the meeting. In some cases, a panelist may be given a waiver but not at this meeting.

[email protected]

SILVER SPRING, MD. – A novel treatment for invasive aspergillosis and invasive mucormycosis gained the support of a Food and Drug Administration advisory panel, although members were more ambivalent about the mucormycosis indication, based on the small amount of data available in those patients.

At a meeting on Jan. 22, the FDA’s Anti-Infective Drugs Advisory Committee voted 11-0 that there was “substantial evidence” that isavuconazonium, an antifungal prodrug, was safe and effective for the treatment of invasive aspergillosis, a life-threatening condition most commonly seen in immunocompromised patients. The drug was studied in a phase III study comparing isavuconazonium to voriconazole, the standard of care, in more than 500 patients.

The panel voted 8-2, with one abstention, that there was substantial evidence it was safe and effective for treating patients with invasive mucormycosis, with panelists voting on both sides of the question citing the study of only 37 patients that used historical controls as an issue. Those supporting approval for mucormycosis said that, if approved, the manufacturer, Astellas, should be required to conduct a phase IV trial further evaluating this treatment for patients with this infection.

Isavuconazonium is a prodrug of isavuconazole, a triazole antifungal, and would be available in an oral capsule formulation and a powder formulation that is reconstituted for intravenous administration (and needs to be administered through an in-line filter in case of particulate formation).

For aspergillosis, “I do believe that this drug provides a reasonable alternative to the current therapies that are available without additional toxicities,” said panelist Dr. Paige Waterman of the Global Emerging Infections Surveillance and Response System at the Walter Reed Army Medical Center, Silver Spring, Md. Other panelists agreed with her recommendations that labeling should make clear that it should not be used in people under age 18 years or in pregnant women, that a filter should be used when administered intravenously, and that labeling should include a statement about the increased risk of hepatotoxicity that also appears in the labeling of other drugs in the same class.

Because it has been associated with a shortened QT interval, she said that screening ECGs should be recommended for patients and that there should be some extra caution when it is prescribed to people who are Asian or of Asian descent, since drug concentrations were slightly higher among Asian patients who received the drug. Other recommendations from panelists included the need to conduct studies of the drug to provide information on therapeutic drug monitoring and in people under 18 years.

For treatment of invasive mucormycosis, an even rarer fungal infection which, in hospitals, is associated with the use of contaminated materials or organ transplantation, the panelists were more hesitant, but those voting in favor of approval cited the significance of the condition and the reasonable efficacy results in the study, stressing that postmarketing studies were critical. Panelists also noted that more clinical data are clearly needed in patients with this infection and the lack of data directly comparing it to amphotericin B – the only FDA-approved drug for this indication – was problematic.

Elizabeth Mechcatie/Frontline Medical News

“This drug really does fill an unmet need; I have high hopes that it is at least as good as amphotericin. But I do think we need more data to confirm that,” said Dr. Michael Neely, chair of antimicrobial stewardship at Children’s Hospital, Los Angeles, who was among those voting in favor of this indication. It appears to have a better safety profile and it would be available in both oral and intravenous formulations, he added. Amphotericin B is available only in an intravenous (IV) formulation.

If approved, isavuconazonium would provide an alternative to voriconazole for treating aspergillosis, and the IV formulation does not contain cyclodextrin, unlike the IV formulation of voriconazole, which limits its use in patients with moderate to severe renal dysfunction, according to Astellas. Safety concerns specific to isavuconazonium include QT-segment shortening and particulate formation in the IV formulation, according to the FDA.

The randomized, double-blind, international, noninferiority study compared treatment with isavuconazonium to voriconazole in 516 adults with invasive aspergillosis. In the randomized study, the mean age of patients was 51 years, 60% were men, most were white, 11% were in the United States and Canada, 20% had had an allogeneic bone marrow transplant, and 70% had an uncontrolled malignancy at baseline (Infect. Drug Resist. 2013;6:16374). The primary effectiveness endpoint, all-cause mortality through day 42, was 19% in those on isavuconazonium, compared with 20% in those on voriconazole. The study met the prespecified noninferiority margin. The rates of deaths and serious adverse events were similar to voriconazole, and there were fewer adverse events in those on isavuconazonium requiring discontinuation of the drug (14% vs. 23%).

Differences in adverse events included lower rates of hepatobiliary disorders, including hyperbilirubinemia, abnormal hepatic function, and jaundice (9% vs. 16%); skin and subcutaneous tissue disorders, including rash, erythema, and drug eruption (34% vs 43%) associated with isavuconazonium, compared with voriconazole. Common adverse events included nausea (28%), vomiting (25%), and diarrhea (24%). Decreases in the QT segment occurred in 7.5% of those on isavuconazonium, compared with 4.5% of those on voriconazole, but were not associated with clinical events.

The prospective, open-label, single-arm study evaluated isavuconazonium in 37 patients with proven or probable mucormycosis infections, whose mean age was 49 years; 59% had a hematologic malignancy, and about 40% were neutropenic at baseline. All-cause mortality at day 42 was almost 38%, which was similar to the mortality rate for amphotericin in the literature, according to Astellas.

There are about 12,000 cases of aspergillosis and about 500 cases of mucormycosis in the United States every year, the company said. In addition to voriconazole, other drugs approved for invasive aspergillosis include amphotericin formulations, itraconazole, and caspofungin. The FDA usually follows the recommendations of its advisory panels. The FDA is expected to make a decision by March 8, according to Astellas, which plans to market the drug as Cresemba if approved. It is also under review in Europe for the same indications.

Panelists were cleared of potential conflicts of interest related to the topic of the meeting. In some cases, a panelist may be given a waiver but not at this meeting.

[email protected]

The striking lack of data on the effectiveness and risks of long-term opioid treatment for the increasing number of people in the United States with chronic pain is reflected in the recommendations made by an expert panel convened by the National Institutes of Health.

To address the role of opioids in the treatment of chronic pain, the panelists met during an NIH Pathways to Prevention workshop in late September where more than 20 invited experts spoke on the topic. The panel produced a draft report shortly after the meeting concluded and received public comments, and the final report has been published on the NIH website. An abridged version of the panel’s final report, which highlights key issues surrounding the use of opioids and chronic pain treatment and provides recommendations on the types of research needed in this area, was published online Jan. 13 in the Annals of Internal Medicine (doi:10.7326/M14-2775).

“The overriding question posed to the panel is whether we as a nation are currently approaching chronic pain in the best possible manner that maximizes effectiveness and minimizes harm. The panel determined that the answer was an unequivocal no,” Dr. David Reuben, the panel chair and lead author of the report, said during a Jan. 16 telebriefing that was held to review the panel’s findings and recommendations. “We hope that the information presented in the panel report will shed light on the issues that need further attention and help facilitate research and better practice to improve outcomes for patients,” added Dr. Reuben, who is chief of geriatric medicine and professor of medicine at the University of California, Los Angeles.

The first recommendation in the panel’s position paper is that federal and non-federal agencies should fund research to identify what types of pain, diseases, and patients “are most likely to benefit and incur harm” from opioids. Agencies should also fund the development and evaluation of multi-disciplinary pain interventions, including cost-benefit analyses, and fund research to “develop and validate research measurement tools” that identify patient risk and outcomes, “related to long-term opioid use that can be adapted for clinical settings,” the panel recommended.

The one recommendation that directly pertains to current clinical practice states that “in the absence of definitive evidence, clinicians and health care systems should follow current guidelines by professional societies about which patients and which types of pain should be treated with opioids and about how best to monitor patients and mitigate risk for harm.” In addition, the report “identifies several key evidence gaps and research priorities that must be addressed so that physicians can recognize patients for whom opioids are most appropriate and use optimal regimens for these patients.”

Considering professional society guidelines is one of the main take home-messages of the report for clinicians, Dr. David Steffens, another panelist and author of the paper, said during the telebriefing. Dr. Steffens, professor and chair of the department of psychiatry, University of Connecticut, Farmington, observed that during the workshop, “the core part of what we heard was an astounding lack of data on efficacy of these drugs,” and noted that the majority of recommendations are “forward-looking in terms of a need to get more data.”

Among the main conclusions of the position paper is that while opioids are “clearly the best treatment for some patients with chronic pain ... there are probably more effective approaches” for many other patients. “The challenge is to identify the conditions in patients for which opioid use is most appropriate, the optimal regimens, the alternatives for those who are unlikely to benefit from opioids, and the best approach to ensuring that every patient’s needs are met by a patient-centered health care system,” the report concludes.

A systematic review of the effectiveness and risks of long-term opioids for chronic pain, prepared specifically for the workshop by the Pacific Northwest Evidence-based Practice Center (EPC) at Oregon Health & Science University, Portland, with funding by the Agency for Healthcare Research and Quality, was also published in the same issue of Annals of Internal Medicine (doi:10.7326/M14-2559).

The review, which evaluated evidence in the medical literature about the effectiveness and risks of long-term opioid therapy (more than 3 months) to treat chronic pain in adults, concluded that “reliable conclusions about the effectiveness of long-term opioid therapy for chronic pain are not possible due to the paucity of research to date.” Moreover, evidence indicating that long-term opioid therapy is associated with significant risks for overdoses, abuse, and other sequelae is increasing, according to the review, which defines chronic pain as pain “lasting longer than 3 months or past the normal time for tissue healing.” Dr. Roger Chou, director of the Pacific Northwest EPC and a physician in the OHSU internal medicine clinic, was the lead author of the review.

An estimated 100 million Americans have chronic pain, of whom about 25 million have moderate-to-severe pain that limits activities and adversely affects their quality of life, according to the position paper. Despite other available treatments, opioids are used for long-term management of chronic pain in an estimated 5-8 million Americans and prescriptions for opioids to treat pain increased from 76 million in 1991 to 219 million in 2011. This increase has been accompanied by a rise in opioid overdoses and treatment for addictions to prescription pain medications. The paper cites Centers for Disease Control and Prevention figures estimating that in 2011, there were more than 17,000 opioid-related overdose deaths.

The NIH Pathways to Prevention Workshop was sponsored by the NIH Office of Disease Prevention, the NIH Pain Consortium, the National Institute on Drug Abuse, and the National Institute of Neurological Disorders and Stroke.

None of the authors of the report had disclosures relevant to the topic. Dr. Chou’s disclosures included having received grants from the AHRQ during the study. He has also been a consultant for the U.S. Department of Health and Human Services and the Providers’ Clinical Support System for Opioid Therapies, which is funded by the Substance Abuse and Mental Health Services Administration.

[email protected]

The striking lack of data on the effectiveness and risks of long-term opioid treatment for the increasing number of people in the United States with chronic pain is reflected in the recommendations made by an expert panel convened by the National Institutes of Health.

To address the role of opioids in the treatment of chronic pain, the panelists met during an NIH Pathways to Prevention workshop in late September where more than 20 invited experts spoke on the topic. The panel produced a draft report shortly after the meeting concluded and received public comments, and the final report has been published on the NIH website. An abridged version of the panel’s final report, which highlights key issues surrounding the use of opioids and chronic pain treatment and provides recommendations on the types of research needed in this area, was published online Jan. 13 in the Annals of Internal Medicine (doi:10.7326/M14-2775).

“The overriding question posed to the panel is whether we as a nation are currently approaching chronic pain in the best possible manner that maximizes effectiveness and minimizes harm. The panel determined that the answer was an unequivocal no,” Dr. David Reuben, the panel chair and lead author of the report, said during a Jan. 16 telebriefing that was held to review the panel’s findings and recommendations. “We hope that the information presented in the panel report will shed light on the issues that need further attention and help facilitate research and better practice to improve outcomes for patients,” added Dr. Reuben, who is chief of geriatric medicine and professor of medicine at the University of California, Los Angeles.

The first recommendation in the panel’s position paper is that federal and non-federal agencies should fund research to identify what types of pain, diseases, and patients “are most likely to benefit and incur harm” from opioids. Agencies should also fund the development and evaluation of multi-disciplinary pain interventions, including cost-benefit analyses, and fund research to “develop and validate research measurement tools” that identify patient risk and outcomes, “related to long-term opioid use that can be adapted for clinical settings,” the panel recommended.

The one recommendation that directly pertains to current clinical practice states that “in the absence of definitive evidence, clinicians and health care systems should follow current guidelines by professional societies about which patients and which types of pain should be treated with opioids and about how best to monitor patients and mitigate risk for harm.” In addition, the report “identifies several key evidence gaps and research priorities that must be addressed so that physicians can recognize patients for whom opioids are most appropriate and use optimal regimens for these patients.”

Considering professional society guidelines is one of the main take home-messages of the report for clinicians, Dr. David Steffens, another panelist and author of the paper, said during the telebriefing. Dr. Steffens, professor and chair of the department of psychiatry, University of Connecticut, Farmington, observed that during the workshop, “the core part of what we heard was an astounding lack of data on efficacy of these drugs,” and noted that the majority of recommendations are “forward-looking in terms of a need to get more data.”

Among the main conclusions of the position paper is that while opioids are “clearly the best treatment for some patients with chronic pain ... there are probably more effective approaches” for many other patients. “The challenge is to identify the conditions in patients for which opioid use is most appropriate, the optimal regimens, the alternatives for those who are unlikely to benefit from opioids, and the best approach to ensuring that every patient’s needs are met by a patient-centered health care system,” the report concludes.

A systematic review of the effectiveness and risks of long-term opioids for chronic pain, prepared specifically for the workshop by the Pacific Northwest Evidence-based Practice Center (EPC) at Oregon Health & Science University, Portland, with funding by the Agency for Healthcare Research and Quality, was also published in the same issue of Annals of Internal Medicine (doi:10.7326/M14-2559).

The review, which evaluated evidence in the medical literature about the effectiveness and risks of long-term opioid therapy (more than 3 months) to treat chronic pain in adults, concluded that “reliable conclusions about the effectiveness of long-term opioid therapy for chronic pain are not possible due to the paucity of research to date.” Moreover, evidence indicating that long-term opioid therapy is associated with significant risks for overdoses, abuse, and other sequelae is increasing, according to the review, which defines chronic pain as pain “lasting longer than 3 months or past the normal time for tissue healing.” Dr. Roger Chou, director of the Pacific Northwest EPC and a physician in the OHSU internal medicine clinic, was the lead author of the review.

An estimated 100 million Americans have chronic pain, of whom about 25 million have moderate-to-severe pain that limits activities and adversely affects their quality of life, according to the position paper. Despite other available treatments, opioids are used for long-term management of chronic pain in an estimated 5-8 million Americans and prescriptions for opioids to treat pain increased from 76 million in 1991 to 219 million in 2011. This increase has been accompanied by a rise in opioid overdoses and treatment for addictions to prescription pain medications. The paper cites Centers for Disease Control and Prevention figures estimating that in 2011, there were more than 17,000 opioid-related overdose deaths.

The NIH Pathways to Prevention Workshop was sponsored by the NIH Office of Disease Prevention, the NIH Pain Consortium, the National Institute on Drug Abuse, and the National Institute of Neurological Disorders and Stroke.

None of the authors of the report had disclosures relevant to the topic. Dr. Chou’s disclosures included having received grants from the AHRQ during the study. He has also been a consultant for the U.S. Department of Health and Human Services and the Providers’ Clinical Support System for Opioid Therapies, which is funded by the Substance Abuse and Mental Health Services Administration.

[email protected]

The striking lack of data on the effectiveness and risks of long-term opioid treatment for the increasing number of people in the United States with chronic pain is reflected in the recommendations made by an expert panel convened by the National Institutes of Health.

To address the role of opioids in the treatment of chronic pain, the panelists met during an NIH Pathways to Prevention workshop in late September where more than 20 invited experts spoke on the topic. The panel produced a draft report shortly after the meeting concluded and received public comments, and the final report has been published on the NIH website. An abridged version of the panel’s final report, which highlights key issues surrounding the use of opioids and chronic pain treatment and provides recommendations on the types of research needed in this area, was published online Jan. 13 in the Annals of Internal Medicine (doi:10.7326/M14-2775).

“The overriding question posed to the panel is whether we as a nation are currently approaching chronic pain in the best possible manner that maximizes effectiveness and minimizes harm. The panel determined that the answer was an unequivocal no,” Dr. David Reuben, the panel chair and lead author of the report, said during a Jan. 16 telebriefing that was held to review the panel’s findings and recommendations. “We hope that the information presented in the panel report will shed light on the issues that need further attention and help facilitate research and better practice to improve outcomes for patients,” added Dr. Reuben, who is chief of geriatric medicine and professor of medicine at the University of California, Los Angeles.

The first recommendation in the panel’s position paper is that federal and non-federal agencies should fund research to identify what types of pain, diseases, and patients “are most likely to benefit and incur harm” from opioids. Agencies should also fund the development and evaluation of multi-disciplinary pain interventions, including cost-benefit analyses, and fund research to “develop and validate research measurement tools” that identify patient risk and outcomes, “related to long-term opioid use that can be adapted for clinical settings,” the panel recommended.

The one recommendation that directly pertains to current clinical practice states that “in the absence of definitive evidence, clinicians and health care systems should follow current guidelines by professional societies about which patients and which types of pain should be treated with opioids and about how best to monitor patients and mitigate risk for harm.” In addition, the report “identifies several key evidence gaps and research priorities that must be addressed so that physicians can recognize patients for whom opioids are most appropriate and use optimal regimens for these patients.”

Considering professional society guidelines is one of the main take home-messages of the report for clinicians, Dr. David Steffens, another panelist and author of the paper, said during the telebriefing. Dr. Steffens, professor and chair of the department of psychiatry, University of Connecticut, Farmington, observed that during the workshop, “the core part of what we heard was an astounding lack of data on efficacy of these drugs,” and noted that the majority of recommendations are “forward-looking in terms of a need to get more data.”

Among the main conclusions of the position paper is that while opioids are “clearly the best treatment for some patients with chronic pain ... there are probably more effective approaches” for many other patients. “The challenge is to identify the conditions in patients for which opioid use is most appropriate, the optimal regimens, the alternatives for those who are unlikely to benefit from opioids, and the best approach to ensuring that every patient’s needs are met by a patient-centered health care system,” the report concludes.

A systematic review of the effectiveness and risks of long-term opioids for chronic pain, prepared specifically for the workshop by the Pacific Northwest Evidence-based Practice Center (EPC) at Oregon Health & Science University, Portland, with funding by the Agency for Healthcare Research and Quality, was also published in the same issue of Annals of Internal Medicine (doi:10.7326/M14-2559).

The review, which evaluated evidence in the medical literature about the effectiveness and risks of long-term opioid therapy (more than 3 months) to treat chronic pain in adults, concluded that “reliable conclusions about the effectiveness of long-term opioid therapy for chronic pain are not possible due to the paucity of research to date.” Moreover, evidence indicating that long-term opioid therapy is associated with significant risks for overdoses, abuse, and other sequelae is increasing, according to the review, which defines chronic pain as pain “lasting longer than 3 months or past the normal time for tissue healing.” Dr. Roger Chou, director of the Pacific Northwest EPC and a physician in the OHSU internal medicine clinic, was the lead author of the review.

An estimated 100 million Americans have chronic pain, of whom about 25 million have moderate-to-severe pain that limits activities and adversely affects their quality of life, according to the position paper. Despite other available treatments, opioids are used for long-term management of chronic pain in an estimated 5-8 million Americans and prescriptions for opioids to treat pain increased from 76 million in 1991 to 219 million in 2011. This increase has been accompanied by a rise in opioid overdoses and treatment for addictions to prescription pain medications. The paper cites Centers for Disease Control and Prevention figures estimating that in 2011, there were more than 17,000 opioid-related overdose deaths.

The NIH Pathways to Prevention Workshop was sponsored by the NIH Office of Disease Prevention, the NIH Pain Consortium, the National Institute on Drug Abuse, and the National Institute of Neurological Disorders and Stroke.

None of the authors of the report had disclosures relevant to the topic. Dr. Chou’s disclosures included having received grants from the AHRQ during the study. He has also been a consultant for the U.S. Department of Health and Human Services and the Providers’ Clinical Support System for Opioid Therapies, which is funded by the Substance Abuse and Mental Health Services Administration.

[email protected]