Head & Neck/Thyroid Cancers

CHICAGO – Partners of patients with human papillomavirus-positive oropharyngeal cancer do not appear to be at an increased risk for HPV-related cancers, investigators reported at the annual meeting of the American Society of Clinical Oncology.

Of 88 female partners of persons with HPV-positive oropharyngeal cancers, 4 were found to be positive for HPV infection, and 2 of the 4 were positive for the oncogenic HPV-16 subtype. The prevalence of HPV infection in this sample was 5%, similar to that of women in the general population (3.6%), reported Gypsyamber D’Souza, Ph.D., an epidemiologist at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Md.

None of the male partners in this small pilot study tested positive for oral HPV 16, but the male sample size was too small to draw significant conclusions about the risks of HPV transmission in men, Dr. D’Souza said.

"This is the first study to examine oral HPV prevalence among spouses of HPV-related oropharyngeal cancer patients, and it’s very reassuring that the oral HPV prevalence was similar to that observed in the general population. This suggests that risk of HPV-related cancer remains low among these spouses," she said in a media briefing prior to her presentation.

The study also supports epidemiologic data showing that although HPV infections are common in the general population, the overwhelming majority of people who are infected will spontaneously clear the virus and not get cancer.

"We certainly will need longer follow-up on how HPV infection and co-infection in the partners will affect patients and the development of cancer, but we recognize this as an important breakthrough in the understanding of the biology of oropharyngeal cancer," commented Dr. Gregory Masters, a medical oncologist at the Helen F. Graham Cancer Center in Newark, Del., who moderated the briefing.

Dr. Marcia S. Brose, a head and neck surgeon at the Hospital of the University of Pennsylvania in Philadelphia, said that despite the handful of male partners, the study sends an important message to patients and their partners.

"As oncologists, we’re not just in the business of the disease itself; we also have to treat the family members and their concerns. If you’re the spouse of someone who has a communicable disease-related cancer, you’re going to have to make decisions that affect your private life, and it means a lot that someone is doing the research that says you don’t have to worry," she said in an interview.

The study was prompted by concerns frequently expressed by patients with oropharyngeal cancer and their spouses/sexual partners about oral transmission of HPV and increased cancer risk, Dr. D’Souza said.

The investigators enrolled 147 men and 19 women (median age 56) with oropharyngeal cancers, and 94 of their spouses or long-term partners.

Oral rinse and gargle samples were collected from all cases and partners in the study at baseline and 1 year later. The samples were tested for the presence of HPV DNA. Imperfect as it is in sensitivity and specificity for HPV, the test is nonetheless the gold standard for detecting HPV in oral cancers, Dr. D’Souza said.

At the time of diagnosis, 65% of patients tested positive for HPV, and 54% of all patients had HPV 16.

At 1 year, however, following completion of therapy, only 5.6% of patients still tested positive for HPV 16.

Overall, the prevalence of oral HPV among partners was 6.5%, comparable to HPV prevalence among the general population in National Health and Nutrition Examination Survery (NHANES) data from 2009-2010. Among male partners, the prevalence of HPV also was similar to that seen among men in the general population (10.1%), but the small number made it difficult if not impossible to draw meaningful conclusions.

No oral or oropharyngeal cancers were detected in partners in an oral cancer screen, but three patients reported having previous partners with oropharyngeal cancer. In addition, five male patients reported having a partner who developed cervical cancer or a precancerous condition (one current partner and two previous partners had cervical cancers, and two current partners had cervical dysplasia).

The study was supported by the Johns Hopkins Innovation Fund. Dr. D’Souza reported receiving research support from Merck, maker of Gardasil.

CHICAGO – Partners of patients with human papillomavirus-positive oropharyngeal cancer do not appear to be at an increased risk for HPV-related cancers, investigators reported at the annual meeting of the American Society of Clinical Oncology.

Of 88 female partners of persons with HPV-positive oropharyngeal cancers, 4 were found to be positive for HPV infection, and 2 of the 4 were positive for the oncogenic HPV-16 subtype. The prevalence of HPV infection in this sample was 5%, similar to that of women in the general population (3.6%), reported Gypsyamber D’Souza, Ph.D., an epidemiologist at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Md.

None of the male partners in this small pilot study tested positive for oral HPV 16, but the male sample size was too small to draw significant conclusions about the risks of HPV transmission in men, Dr. D’Souza said.

"This is the first study to examine oral HPV prevalence among spouses of HPV-related oropharyngeal cancer patients, and it’s very reassuring that the oral HPV prevalence was similar to that observed in the general population. This suggests that risk of HPV-related cancer remains low among these spouses," she said in a media briefing prior to her presentation.

The study also supports epidemiologic data showing that although HPV infections are common in the general population, the overwhelming majority of people who are infected will spontaneously clear the virus and not get cancer.

"We certainly will need longer follow-up on how HPV infection and co-infection in the partners will affect patients and the development of cancer, but we recognize this as an important breakthrough in the understanding of the biology of oropharyngeal cancer," commented Dr. Gregory Masters, a medical oncologist at the Helen F. Graham Cancer Center in Newark, Del., who moderated the briefing.

Dr. Marcia S. Brose, a head and neck surgeon at the Hospital of the University of Pennsylvania in Philadelphia, said that despite the handful of male partners, the study sends an important message to patients and their partners.

"As oncologists, we’re not just in the business of the disease itself; we also have to treat the family members and their concerns. If you’re the spouse of someone who has a communicable disease-related cancer, you’re going to have to make decisions that affect your private life, and it means a lot that someone is doing the research that says you don’t have to worry," she said in an interview.

The study was prompted by concerns frequently expressed by patients with oropharyngeal cancer and their spouses/sexual partners about oral transmission of HPV and increased cancer risk, Dr. D’Souza said.

The investigators enrolled 147 men and 19 women (median age 56) with oropharyngeal cancers, and 94 of their spouses or long-term partners.

Oral rinse and gargle samples were collected from all cases and partners in the study at baseline and 1 year later. The samples were tested for the presence of HPV DNA. Imperfect as it is in sensitivity and specificity for HPV, the test is nonetheless the gold standard for detecting HPV in oral cancers, Dr. D’Souza said.

At the time of diagnosis, 65% of patients tested positive for HPV, and 54% of all patients had HPV 16.

At 1 year, however, following completion of therapy, only 5.6% of patients still tested positive for HPV 16.

Overall, the prevalence of oral HPV among partners was 6.5%, comparable to HPV prevalence among the general population in National Health and Nutrition Examination Survery (NHANES) data from 2009-2010. Among male partners, the prevalence of HPV also was similar to that seen among men in the general population (10.1%), but the small number made it difficult if not impossible to draw meaningful conclusions.

No oral or oropharyngeal cancers were detected in partners in an oral cancer screen, but three patients reported having previous partners with oropharyngeal cancer. In addition, five male patients reported having a partner who developed cervical cancer or a precancerous condition (one current partner and two previous partners had cervical cancers, and two current partners had cervical dysplasia).

The study was supported by the Johns Hopkins Innovation Fund. Dr. D’Souza reported receiving research support from Merck, maker of Gardasil.

CHICAGO – Partners of patients with human papillomavirus-positive oropharyngeal cancer do not appear to be at an increased risk for HPV-related cancers, investigators reported at the annual meeting of the American Society of Clinical Oncology.

Of 88 female partners of persons with HPV-positive oropharyngeal cancers, 4 were found to be positive for HPV infection, and 2 of the 4 were positive for the oncogenic HPV-16 subtype. The prevalence of HPV infection in this sample was 5%, similar to that of women in the general population (3.6%), reported Gypsyamber D’Souza, Ph.D., an epidemiologist at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Md.

None of the male partners in this small pilot study tested positive for oral HPV 16, but the male sample size was too small to draw significant conclusions about the risks of HPV transmission in men, Dr. D’Souza said.

"This is the first study to examine oral HPV prevalence among spouses of HPV-related oropharyngeal cancer patients, and it’s very reassuring that the oral HPV prevalence was similar to that observed in the general population. This suggests that risk of HPV-related cancer remains low among these spouses," she said in a media briefing prior to her presentation.

The study also supports epidemiologic data showing that although HPV infections are common in the general population, the overwhelming majority of people who are infected will spontaneously clear the virus and not get cancer.

"We certainly will need longer follow-up on how HPV infection and co-infection in the partners will affect patients and the development of cancer, but we recognize this as an important breakthrough in the understanding of the biology of oropharyngeal cancer," commented Dr. Gregory Masters, a medical oncologist at the Helen F. Graham Cancer Center in Newark, Del., who moderated the briefing.

Dr. Marcia S. Brose, a head and neck surgeon at the Hospital of the University of Pennsylvania in Philadelphia, said that despite the handful of male partners, the study sends an important message to patients and their partners.

"As oncologists, we’re not just in the business of the disease itself; we also have to treat the family members and their concerns. If you’re the spouse of someone who has a communicable disease-related cancer, you’re going to have to make decisions that affect your private life, and it means a lot that someone is doing the research that says you don’t have to worry," she said in an interview.

The study was prompted by concerns frequently expressed by patients with oropharyngeal cancer and their spouses/sexual partners about oral transmission of HPV and increased cancer risk, Dr. D’Souza said.

The investigators enrolled 147 men and 19 women (median age 56) with oropharyngeal cancers, and 94 of their spouses or long-term partners.

Oral rinse and gargle samples were collected from all cases and partners in the study at baseline and 1 year later. The samples were tested for the presence of HPV DNA. Imperfect as it is in sensitivity and specificity for HPV, the test is nonetheless the gold standard for detecting HPV in oral cancers, Dr. D’Souza said.

At the time of diagnosis, 65% of patients tested positive for HPV, and 54% of all patients had HPV 16.

At 1 year, however, following completion of therapy, only 5.6% of patients still tested positive for HPV 16.

Overall, the prevalence of oral HPV among partners was 6.5%, comparable to HPV prevalence among the general population in National Health and Nutrition Examination Survery (NHANES) data from 2009-2010. Among male partners, the prevalence of HPV also was similar to that seen among men in the general population (10.1%), but the small number made it difficult if not impossible to draw meaningful conclusions.

No oral or oropharyngeal cancers were detected in partners in an oral cancer screen, but three patients reported having previous partners with oropharyngeal cancer. In addition, five male patients reported having a partner who developed cervical cancer or a precancerous condition (one current partner and two previous partners had cervical cancers, and two current partners had cervical dysplasia).

The study was supported by the Johns Hopkins Innovation Fund. Dr. D’Souza reported receiving research support from Merck, maker of Gardasil.

NEW ORLEANS – Dexamethasone was more effective than was placebo in relieving cancer-related fatigue in a double-blind randomized trial of patients with advanced cancer.

After 14 days of treatment, scores on the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue subscale improved by nearly 6 points in the dexamethasone group (9.0 vs. 3.1; P = .008).

Patrice Wendling/IMNG Medical Media

"[Treatment] duration is very important in our patient population because when they are referred to us, it’s very late. They typically have a survival of just 28 to 7 days," Dr. Sriram Yennu said at the annual meeting of the American Academy of Hospice and Palliative Medicine.

Although 20%-50% of palliative care patients receive some form of corticosteroid, no steroid study to date has used cancer-related fatigue (CRF) as a primary outcome or assessed CRF with a validated outcome measure, he said. Fatigue is ubiquitous, however, contributing up to one-third of symptom distress in patients with advanced cancer.

The study enrolled 132 outpatients with a life expectancy of at least 4 weeks with three or more cancer-related symptoms (fatigue, pain, nausea, loss of appetite, depression, anxiety, or sleep disturbance), and randomly assigned them to oral dexamethasone 4 mg twice daily or placebo for 14 days.

The most common diagnosis was head and neck/lung cancer in 45 patients, followed by gastrointestinal cancer in 39, breast cancer in 13, and genitourinary in 10. Median patient age was 60; 81 patients were white, and the average FACIT fatigue score was 19.6, where 52 denotes no fatigue and 0 is severe fatigue.

Among 84 evaluable patients, total scores on FACIT favored the dexamethasone group (18.16 vs. 7.87; P = .03), as did scores on its physical subscale (5.25 vs. 1.32; P = .002), said Dr. Yennu of the department of palliative care and rehabilitation medicine, University of Texas MD Anderson Cancer Center, Houston.

Scores on the physical domain of the Edmonton Symptom Assessment Scale (ESAS) were better in the dexamethasone group than in the placebo group (–10.15 vs. –5.39; P = .04), according to the study, which earned Dr. Yennu a young investigator award.

Notably, scores were similar between the dexamethasone and placebo groups on the emotional subscale of FACIT (1.85 vs. 1.18; P = .49) and the ESAS psychological subscale (–1.48 vs. –2.08; P = .76). The emotional domain of the FACIT-F is measured by six items using a 0-4 scale where 0 is "not at all" and 4 includes statements like "I am losing hope in the fight against my illness." The finding suggests that the improvement in fatigue was likely not just a euphoric effect, as observed before in other steroid trials, Dr. Yennu said.

He expressed concern that corticosteroid use would increase toxicity, particularly insomnia, but no significant differences were observed between the dexamethasone and placebo groups regarding insomnia (3 vs. 4), overall adverse events (41 vs. 44) or serious adverse events (17 vs. 11).

Larger, long-term safety and efficacy studies are needed to address steroid dose and duration, and whether dexamethasone should be coupled with interventions targeting the psychological domain, he said. A 3-point difference in the FACIT is considered clinically important, but research in press in the Journal of Clinical Oncology, by Dr. Yennu and his colleagues, suggests a 10-point difference is more meaningful.

The American Cancer Society supported the study. Dr. Yennu reported having no financial disclosures.

[email protected]

NEW ORLEANS – Dexamethasone was more effective than was placebo in relieving cancer-related fatigue in a double-blind randomized trial of patients with advanced cancer.

After 14 days of treatment, scores on the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue subscale improved by nearly 6 points in the dexamethasone group (9.0 vs. 3.1; P = .008).

Patrice Wendling/IMNG Medical Media

"[Treatment] duration is very important in our patient population because when they are referred to us, it’s very late. They typically have a survival of just 28 to 7 days," Dr. Sriram Yennu said at the annual meeting of the American Academy of Hospice and Palliative Medicine.

Although 20%-50% of palliative care patients receive some form of corticosteroid, no steroid study to date has used cancer-related fatigue (CRF) as a primary outcome or assessed CRF with a validated outcome measure, he said. Fatigue is ubiquitous, however, contributing up to one-third of symptom distress in patients with advanced cancer.

The study enrolled 132 outpatients with a life expectancy of at least 4 weeks with three or more cancer-related symptoms (fatigue, pain, nausea, loss of appetite, depression, anxiety, or sleep disturbance), and randomly assigned them to oral dexamethasone 4 mg twice daily or placebo for 14 days.

The most common diagnosis was head and neck/lung cancer in 45 patients, followed by gastrointestinal cancer in 39, breast cancer in 13, and genitourinary in 10. Median patient age was 60; 81 patients were white, and the average FACIT fatigue score was 19.6, where 52 denotes no fatigue and 0 is severe fatigue.

Among 84 evaluable patients, total scores on FACIT favored the dexamethasone group (18.16 vs. 7.87; P = .03), as did scores on its physical subscale (5.25 vs. 1.32; P = .002), said Dr. Yennu of the department of palliative care and rehabilitation medicine, University of Texas MD Anderson Cancer Center, Houston.

Scores on the physical domain of the Edmonton Symptom Assessment Scale (ESAS) were better in the dexamethasone group than in the placebo group (–10.15 vs. –5.39; P = .04), according to the study, which earned Dr. Yennu a young investigator award.

Notably, scores were similar between the dexamethasone and placebo groups on the emotional subscale of FACIT (1.85 vs. 1.18; P = .49) and the ESAS psychological subscale (–1.48 vs. –2.08; P = .76). The emotional domain of the FACIT-F is measured by six items using a 0-4 scale where 0 is "not at all" and 4 includes statements like "I am losing hope in the fight against my illness." The finding suggests that the improvement in fatigue was likely not just a euphoric effect, as observed before in other steroid trials, Dr. Yennu said.

He expressed concern that corticosteroid use would increase toxicity, particularly insomnia, but no significant differences were observed between the dexamethasone and placebo groups regarding insomnia (3 vs. 4), overall adverse events (41 vs. 44) or serious adverse events (17 vs. 11).

Larger, long-term safety and efficacy studies are needed to address steroid dose and duration, and whether dexamethasone should be coupled with interventions targeting the psychological domain, he said. A 3-point difference in the FACIT is considered clinically important, but research in press in the Journal of Clinical Oncology, by Dr. Yennu and his colleagues, suggests a 10-point difference is more meaningful.

The American Cancer Society supported the study. Dr. Yennu reported having no financial disclosures.

[email protected]

NEW ORLEANS – Dexamethasone was more effective than was placebo in relieving cancer-related fatigue in a double-blind randomized trial of patients with advanced cancer.

After 14 days of treatment, scores on the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue subscale improved by nearly 6 points in the dexamethasone group (9.0 vs. 3.1; P = .008).

Patrice Wendling/IMNG Medical Media

"[Treatment] duration is very important in our patient population because when they are referred to us, it’s very late. They typically have a survival of just 28 to 7 days," Dr. Sriram Yennu said at the annual meeting of the American Academy of Hospice and Palliative Medicine.

Although 20%-50% of palliative care patients receive some form of corticosteroid, no steroid study to date has used cancer-related fatigue (CRF) as a primary outcome or assessed CRF with a validated outcome measure, he said. Fatigue is ubiquitous, however, contributing up to one-third of symptom distress in patients with advanced cancer.

The study enrolled 132 outpatients with a life expectancy of at least 4 weeks with three or more cancer-related symptoms (fatigue, pain, nausea, loss of appetite, depression, anxiety, or sleep disturbance), and randomly assigned them to oral dexamethasone 4 mg twice daily or placebo for 14 days.

The most common diagnosis was head and neck/lung cancer in 45 patients, followed by gastrointestinal cancer in 39, breast cancer in 13, and genitourinary in 10. Median patient age was 60; 81 patients were white, and the average FACIT fatigue score was 19.6, where 52 denotes no fatigue and 0 is severe fatigue.

Among 84 evaluable patients, total scores on FACIT favored the dexamethasone group (18.16 vs. 7.87; P = .03), as did scores on its physical subscale (5.25 vs. 1.32; P = .002), said Dr. Yennu of the department of palliative care and rehabilitation medicine, University of Texas MD Anderson Cancer Center, Houston.

Scores on the physical domain of the Edmonton Symptom Assessment Scale (ESAS) were better in the dexamethasone group than in the placebo group (–10.15 vs. –5.39; P = .04), according to the study, which earned Dr. Yennu a young investigator award.

Notably, scores were similar between the dexamethasone and placebo groups on the emotional subscale of FACIT (1.85 vs. 1.18; P = .49) and the ESAS psychological subscale (–1.48 vs. –2.08; P = .76). The emotional domain of the FACIT-F is measured by six items using a 0-4 scale where 0 is "not at all" and 4 includes statements like "I am losing hope in the fight against my illness." The finding suggests that the improvement in fatigue was likely not just a euphoric effect, as observed before in other steroid trials, Dr. Yennu said.

He expressed concern that corticosteroid use would increase toxicity, particularly insomnia, but no significant differences were observed between the dexamethasone and placebo groups regarding insomnia (3 vs. 4), overall adverse events (41 vs. 44) or serious adverse events (17 vs. 11).

Larger, long-term safety and efficacy studies are needed to address steroid dose and duration, and whether dexamethasone should be coupled with interventions targeting the psychological domain, he said. A 3-point difference in the FACIT is considered clinically important, but research in press in the Journal of Clinical Oncology, by Dr. Yennu and his colleagues, suggests a 10-point difference is more meaningful.

The American Cancer Society supported the study. Dr. Yennu reported having no financial disclosures.

[email protected]

Community Oncology Editor Dr. Debra Patt spoke with Dr. Ezra Cohen at the Oncology Practice Summit in Las Vegas about the HPV epidemic and its effect on the pathophysiology and treatment of head and neck cancers.

The Oncology Practice Summit was the 8th annual meeting of Community Oncology, the journal of clinical issues in community practice.  Dr. Patt was a co-chair of the Summit, which was hosted this year by Community Oncology as well as The Journal of Supportive Oncology and The Oncology Report.

Community Oncology Editor Dr. Debra Patt spoke with Dr. Ezra Cohen at the Oncology Practice Summit in Las Vegas about the HPV epidemic and its effect on the pathophysiology and treatment of head and neck cancers.

The Oncology Practice Summit was the 8th annual meeting of Community Oncology, the journal of clinical issues in community practice.  Dr. Patt was a co-chair of the Summit, which was hosted this year by Community Oncology as well as The Journal of Supportive Oncology and The Oncology Report.

Community Oncology Editor Dr. Debra Patt spoke with Dr. Ezra Cohen at the Oncology Practice Summit in Las Vegas about the HPV epidemic and its effect on the pathophysiology and treatment of head and neck cancers.

The Oncology Practice Summit was the 8th annual meeting of Community Oncology, the journal of clinical issues in community practice.  Dr. Patt was a co-chair of the Summit, which was hosted this year by Community Oncology as well as The Journal of Supportive Oncology and The Oncology Report.

LOS ANGELES – Prophylactic escitalopram reduces the risk for depression in patients undergoing treatment for head and neck cancer, according to findings from a randomized placebo-controlled trial involving 148 patients.

Of those randomized to receive the selective serotonin reuptake inhibitor, 10% developed moderate to severe depression during the course of their cancer treatment, compared with 24.6% of those who received placebo, Dr. William J. Burke reported in a poster at the annual meeting of the American Association for Geriatric Psychiatry.

After adjustment for age, baseline smoking status, and stratification variables, including gender, cancer site, cancer stage, and primary treatment modality, those receiving active treatment remained significantly less likely to develop depression (hazard ratio, 0.37), said Dr. Burke of the University of Nebraska Medical Center, Omaha.

Of note, patients undergoing radiotherapy as the primary treatment modality were significantly more likely than those undergoing surgery as the primary treatment modality to develop depression (hazard ratio, 3.6).

Patients in the escitalopram group who did not become depressed during the course of the study reported a significantly better quality of life for 3 consecutive months after escitalopram cessation than those in either the treatment or placebo group who did develop depression, Dr. Burke noted.

Patients included in this double-blind study had head and neck cancers and were about to enter cancer treatment. Depression was assessed using the QIDS-SR(Quick Inventory of Depressive Symptomatology-Self Rated).

The findings have important implications for the management of patients entering treatment for head and neck cancer, which can be a particularly devastating disease. For example, larynx and tongue cancers comprise only 2% of all cancers, but patients with these cancers commit 19% of all cancer-related suicides, Dr. Burke noted.

Up to half of all patients with head and neck cancer develop major depressive disorder, which can adversely affect adherence to treatment, reduce quality of life, and result in significant morbidity and reduced survival.

"Preventing depression during the course of cancer treatment may, thus, be of great benefit," he said.

The project was supported by a grant from the National Institute of Mental Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH or the National Institutes of Health. Additional support was provided by a research support fund grant from the Nebraska Medical Center and the University of Nebraska Medical Center. Forest Pharmaceuticals provided the matching placebo and drugs.

LOS ANGELES – Prophylactic escitalopram reduces the risk for depression in patients undergoing treatment for head and neck cancer, according to findings from a randomized placebo-controlled trial involving 148 patients.

Of those randomized to receive the selective serotonin reuptake inhibitor, 10% developed moderate to severe depression during the course of their cancer treatment, compared with 24.6% of those who received placebo, Dr. William J. Burke reported in a poster at the annual meeting of the American Association for Geriatric Psychiatry.

After adjustment for age, baseline smoking status, and stratification variables, including gender, cancer site, cancer stage, and primary treatment modality, those receiving active treatment remained significantly less likely to develop depression (hazard ratio, 0.37), said Dr. Burke of the University of Nebraska Medical Center, Omaha.

Of note, patients undergoing radiotherapy as the primary treatment modality were significantly more likely than those undergoing surgery as the primary treatment modality to develop depression (hazard ratio, 3.6).

Patients in the escitalopram group who did not become depressed during the course of the study reported a significantly better quality of life for 3 consecutive months after escitalopram cessation than those in either the treatment or placebo group who did develop depression, Dr. Burke noted.

Patients included in this double-blind study had head and neck cancers and were about to enter cancer treatment. Depression was assessed using the QIDS-SR(Quick Inventory of Depressive Symptomatology-Self Rated).

The findings have important implications for the management of patients entering treatment for head and neck cancer, which can be a particularly devastating disease. For example, larynx and tongue cancers comprise only 2% of all cancers, but patients with these cancers commit 19% of all cancer-related suicides, Dr. Burke noted.

Up to half of all patients with head and neck cancer develop major depressive disorder, which can adversely affect adherence to treatment, reduce quality of life, and result in significant morbidity and reduced survival.

"Preventing depression during the course of cancer treatment may, thus, be of great benefit," he said.

The project was supported by a grant from the National Institute of Mental Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH or the National Institutes of Health. Additional support was provided by a research support fund grant from the Nebraska Medical Center and the University of Nebraska Medical Center. Forest Pharmaceuticals provided the matching placebo and drugs.

LOS ANGELES – Prophylactic escitalopram reduces the risk for depression in patients undergoing treatment for head and neck cancer, according to findings from a randomized placebo-controlled trial involving 148 patients.

Of those randomized to receive the selective serotonin reuptake inhibitor, 10% developed moderate to severe depression during the course of their cancer treatment, compared with 24.6% of those who received placebo, Dr. William J. Burke reported in a poster at the annual meeting of the American Association for Geriatric Psychiatry.

After adjustment for age, baseline smoking status, and stratification variables, including gender, cancer site, cancer stage, and primary treatment modality, those receiving active treatment remained significantly less likely to develop depression (hazard ratio, 0.37), said Dr. Burke of the University of Nebraska Medical Center, Omaha.

Of note, patients undergoing radiotherapy as the primary treatment modality were significantly more likely than those undergoing surgery as the primary treatment modality to develop depression (hazard ratio, 3.6).

Patients in the escitalopram group who did not become depressed during the course of the study reported a significantly better quality of life for 3 consecutive months after escitalopram cessation than those in either the treatment or placebo group who did develop depression, Dr. Burke noted.

Patients included in this double-blind study had head and neck cancers and were about to enter cancer treatment. Depression was assessed using the QIDS-SR(Quick Inventory of Depressive Symptomatology-Self Rated).

The findings have important implications for the management of patients entering treatment for head and neck cancer, which can be a particularly devastating disease. For example, larynx and tongue cancers comprise only 2% of all cancers, but patients with these cancers commit 19% of all cancer-related suicides, Dr. Burke noted.

Up to half of all patients with head and neck cancer develop major depressive disorder, which can adversely affect adherence to treatment, reduce quality of life, and result in significant morbidity and reduced survival.

"Preventing depression during the course of cancer treatment may, thus, be of great benefit," he said.

The project was supported by a grant from the National Institute of Mental Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH or the National Institutes of Health. Additional support was provided by a research support fund grant from the Nebraska Medical Center and the University of Nebraska Medical Center. Forest Pharmaceuticals provided the matching placebo and drugs.

SAN FRANCISCO – A phase II/III clinical trial of adding cetuximab to chemoradiotherapy for localized esophageal cancer was stopped early when interim results showed greater toxicity, less completion of chemoradiotherapy, and worse survival with cetuximab.

Patients had been randomized to potentially curative treatment with cisplatin, capecitabine, and radiation, with or without cetuximab (Erbitux). Six months of follow-up on 258 patients found significantly lower median overall survival in the cetuximab arm compared with the control group (22.1 months vs. 25.4 months) and fewer patients free of treatment failure (66% vs. 77%), Dr. Thomas Crosby reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO).

Sherry Boschert/IMNG Medical Media

The number of patients lost to follow-up before 26 weeks was similar between groups: 10 in the cetuximab group and 8 in the control group, he added.

Significantly fewer patients in the cetuximab arm were able to receive the full protocol dose of radiotherapy compared with the control arm (75% vs. 86%) and to complete all four cycles of cisplatin and capecitabine at full doses (77% vs. 90%) or reduced doses (69% vs. 85%), reported Dr. Crosby of Velindre Hospital, Cardiff, Wales.

The cetuximab group also showed significantly higher rates of grade 3 or 4 nonhematologic toxicities (78%) compared with the control arm (63%), primarily because of increases in cardiac toxicities (6% vs. 2%), dermatologic toxicities (22% vs. 4%), and metabolic toxicities (24% vs. 11%).

"The addition of cetuximab cannot be recommended to standard definitive chemoradiotherapy in the treatment of unselected patients with esophageal cancer," Dr. Crosby said.

All patients were to receive four cycles of cisplatin 60 mg/m² on day 1 and capecitabine 625 mg/m² daily on days 1-21, with cycles three and four given concurrently with radiotherapy (60 Gy in 25 fractions). The cetuximab group also received 400 mg/m² of the drug on day 1 of cycle three, followed by cetuximab 250 mg/m² weekly.

Patients in the multicenter study, known as the SCOPE 1 trial, had a median age of 67 years in both groups.

Survival outcomes associated with chemoradiotherapy for localized, poor-prognosis esophageal cancer in SCOPE 1 were better than results previously reported in trials of radiotherapy or surgery for these cancers, he noted. Future research should look at improving definitive chemoradiotherapy by identifying biomarkers to help select patients for treatment and incorporating newer radiology techniques to intensify treatment, he suggested.

Definitive chemoradiotherapy is used in the United Kingdom predominantly for patients with esophageal cancer who are not candidates for surgery and is considered a standard of care for patients with localized squamous cell carcinoma of the esophagus, Dr. Crosby said.

Other previous studies have reported that cetuximab improved outcomes when added to chemotherapy for advanced colorectal or head and neck cancers, and when added to radiotherapy for localized squamous cell carcinomas of the head and neck, he said. A separate study recently reported worse outcomes when cetuximab was added to first-line chemotherapy for gastric cancer.

Dr. Crosby reported having no relevant financial disclosures. Cetuximab is a product of ImClone, a subsidiary of Eli Lilly and Bristol-Myers Squibb, that is licensed to Merck KGaA for marketing outside the United States. Some of his associates reported receiving research funding from Merck, AstraZeneca, or Roche.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – A phase II/III clinical trial of adding cetuximab to chemoradiotherapy for localized esophageal cancer was stopped early when interim results showed greater toxicity, less completion of chemoradiotherapy, and worse survival with cetuximab.

Patients had been randomized to potentially curative treatment with cisplatin, capecitabine, and radiation, with or without cetuximab (Erbitux). Six months of follow-up on 258 patients found significantly lower median overall survival in the cetuximab arm compared with the control group (22.1 months vs. 25.4 months) and fewer patients free of treatment failure (66% vs. 77%), Dr. Thomas Crosby reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO).

Sherry Boschert/IMNG Medical Media

The number of patients lost to follow-up before 26 weeks was similar between groups: 10 in the cetuximab group and 8 in the control group, he added.

Significantly fewer patients in the cetuximab arm were able to receive the full protocol dose of radiotherapy compared with the control arm (75% vs. 86%) and to complete all four cycles of cisplatin and capecitabine at full doses (77% vs. 90%) or reduced doses (69% vs. 85%), reported Dr. Crosby of Velindre Hospital, Cardiff, Wales.

The cetuximab group also showed significantly higher rates of grade 3 or 4 nonhematologic toxicities (78%) compared with the control arm (63%), primarily because of increases in cardiac toxicities (6% vs. 2%), dermatologic toxicities (22% vs. 4%), and metabolic toxicities (24% vs. 11%).

"The addition of cetuximab cannot be recommended to standard definitive chemoradiotherapy in the treatment of unselected patients with esophageal cancer," Dr. Crosby said.

All patients were to receive four cycles of cisplatin 60 mg/m² on day 1 and capecitabine 625 mg/m² daily on days 1-21, with cycles three and four given concurrently with radiotherapy (60 Gy in 25 fractions). The cetuximab group also received 400 mg/m² of the drug on day 1 of cycle three, followed by cetuximab 250 mg/m² weekly.

Patients in the multicenter study, known as the SCOPE 1 trial, had a median age of 67 years in both groups.

Survival outcomes associated with chemoradiotherapy for localized, poor-prognosis esophageal cancer in SCOPE 1 were better than results previously reported in trials of radiotherapy or surgery for these cancers, he noted. Future research should look at improving definitive chemoradiotherapy by identifying biomarkers to help select patients for treatment and incorporating newer radiology techniques to intensify treatment, he suggested.

Definitive chemoradiotherapy is used in the United Kingdom predominantly for patients with esophageal cancer who are not candidates for surgery and is considered a standard of care for patients with localized squamous cell carcinoma of the esophagus, Dr. Crosby said.

Other previous studies have reported that cetuximab improved outcomes when added to chemotherapy for advanced colorectal or head and neck cancers, and when added to radiotherapy for localized squamous cell carcinomas of the head and neck, he said. A separate study recently reported worse outcomes when cetuximab was added to first-line chemotherapy for gastric cancer.

Dr. Crosby reported having no relevant financial disclosures. Cetuximab is a product of ImClone, a subsidiary of Eli Lilly and Bristol-Myers Squibb, that is licensed to Merck KGaA for marketing outside the United States. Some of his associates reported receiving research funding from Merck, AstraZeneca, or Roche.

[email protected]

On Twitter @sherryboschert

SAN FRANCISCO – A phase II/III clinical trial of adding cetuximab to chemoradiotherapy for localized esophageal cancer was stopped early when interim results showed greater toxicity, less completion of chemoradiotherapy, and worse survival with cetuximab.

Patients had been randomized to potentially curative treatment with cisplatin, capecitabine, and radiation, with or without cetuximab (Erbitux). Six months of follow-up on 258 patients found significantly lower median overall survival in the cetuximab arm compared with the control group (22.1 months vs. 25.4 months) and fewer patients free of treatment failure (66% vs. 77%), Dr. Thomas Crosby reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO).

Sherry Boschert/IMNG Medical Media

The number of patients lost to follow-up before 26 weeks was similar between groups: 10 in the cetuximab group and 8 in the control group, he added.

Significantly fewer patients in the cetuximab arm were able to receive the full protocol dose of radiotherapy compared with the control arm (75% vs. 86%) and to complete all four cycles of cisplatin and capecitabine at full doses (77% vs. 90%) or reduced doses (69% vs. 85%), reported Dr. Crosby of Velindre Hospital, Cardiff, Wales.

The cetuximab group also showed significantly higher rates of grade 3 or 4 nonhematologic toxicities (78%) compared with the control arm (63%), primarily because of increases in cardiac toxicities (6% vs. 2%), dermatologic toxicities (22% vs. 4%), and metabolic toxicities (24% vs. 11%).

"The addition of cetuximab cannot be recommended to standard definitive chemoradiotherapy in the treatment of unselected patients with esophageal cancer," Dr. Crosby said.

All patients were to receive four cycles of cisplatin 60 mg/m² on day 1 and capecitabine 625 mg/m² daily on days 1-21, with cycles three and four given concurrently with radiotherapy (60 Gy in 25 fractions). The cetuximab group also received 400 mg/m² of the drug on day 1 of cycle three, followed by cetuximab 250 mg/m² weekly.

Patients in the multicenter study, known as the SCOPE 1 trial, had a median age of 67 years in both groups.

Survival outcomes associated with chemoradiotherapy for localized, poor-prognosis esophageal cancer in SCOPE 1 were better than results previously reported in trials of radiotherapy or surgery for these cancers, he noted. Future research should look at improving definitive chemoradiotherapy by identifying biomarkers to help select patients for treatment and incorporating newer radiology techniques to intensify treatment, he suggested.

Definitive chemoradiotherapy is used in the United Kingdom predominantly for patients with esophageal cancer who are not candidates for surgery and is considered a standard of care for patients with localized squamous cell carcinoma of the esophagus, Dr. Crosby said.

Other previous studies have reported that cetuximab improved outcomes when added to chemotherapy for advanced colorectal or head and neck cancers, and when added to radiotherapy for localized squamous cell carcinomas of the head and neck, he said. A separate study recently reported worse outcomes when cetuximab was added to first-line chemotherapy for gastric cancer.

Dr. Crosby reported having no relevant financial disclosures. Cetuximab is a product of ImClone, a subsidiary of Eli Lilly and Bristol-Myers Squibb, that is licensed to Merck KGaA for marketing outside the United States. Some of his associates reported receiving research funding from Merck, AstraZeneca, or Roche.

[email protected]

On Twitter @sherryboschert

Cabozantinib, a kinase inhibitor, has been approved for the treatment of progressive, metastatic medullary thyroid cancer, on the basis of the results of an international study of 330 patients, the Food and Drug Administration has announced.

This is the second drug approved by the FDA for this indication in the past 2 years; the first was vandetanib (Caprelsa), approved in April 2011. Before these approvals, "patients with this rare and difficult to treat disease had limited therapeutic treatment options," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in the FDA’s Nov. 29 statement announcing the approval.

Cabozantinib will be marketed as Cometriq by Exelixis Inc. The recommended dose is 140 mg orally, without food (people taking the drug should not eat for at least 2 hours before and at least 1 hour after taking it). Exelixis is planning to make the drug available in late January, at an average wholesale price of $9,900 for a 28-day supply, according to the company.

In the EXAM study of 330 patients with metastatic medullary thyroid cancer, with evidence of actively progressive disease within 14 months of enrollment, the median progression-free survival was 11.2 months among those treated with cabozantinib, compared with 4 months among those on placebo, a statistically significant difference, according to the prescribing information. Partial responses were observed among 27% of those on cabozantinib but none of those on placebo, and the median duration of the objective response was 14.7 months among those on cabozantinib. At the planned interim analysis, there was no statistically significant difference in overall survival between the two groups.

The most common adverse events, reported in at least 25% of patients treated with cabozantinib, were diarrhea; stomatitis, palmar-plantar erythrodysesthesia syndrome; decreases in weight and appetite; nausea; fatigue; oral pain; hair color changes; dysgeusia; hypertension; abdominal pain; and constipation. The most common laboratory abnormalities, reported in at least 25% of patients, were increased AST, increased ALT, lymphopenia, increased alkaline phosphatase, hypocalcemia, neutropenia, thrombocytopenia, hypophosphatemia, and hyperbilirubinemia.

The prescribing information includes a boxed warning about severe and sometimes fatal hemorrhage (3%), and gastrointestinal perforations (3%) and fistulas (1%) were reported in patients treated with the drug.

The review of this drug was a priority review, completed in 6 months, which is used for drugs "that may offer major advances in treatment or that provide a treatment when no adequate therapy exists," the FDA statement said. The drug has also been designated an orphan drug, because medullary thyroid cancer is considered a rare disease.

As part of its postmarketing commitments, the FDA has requested that the company submit the final overall survival results of the study, expected to be submitted in December 2014, according to the agency’s approval letter. The letter also lists other postmarketing commitments, including the completion of a study comparing the approved dose of "a biologically active and potentially safer lower daily cabozantinib dose" in patients with progressive medullary thyroid cancer.

Cabozantinib is a kinase inhibitor that inhibits the activity of RET, MET, and other tyrosine kinases, which "are involved in both normal cellular function, and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment," according to the Exelixis statement announcing approval

The company also announced on Nov. 29 that the application for approval of cabozantinib, also based on the EXAM study, has been accepted by the European Medicines Agency for approval in the European Union.

The FDA statement cites estimates from the National Cancer Institute that 56,460 people will be diagnosed with thyroid cancer this year in the United States, and 1,780 will die from the disease, and about 4% percent of thyroid cancers are medullary thyroid cancer.

The drug’s label is available on the FDA website. Serious adverse events associated with the drug should be reported to the FDA’s MedWatch site or at 800-332-1088.

Cabozantinib, a kinase inhibitor, has been approved for the treatment of progressive, metastatic medullary thyroid cancer, on the basis of the results of an international study of 330 patients, the Food and Drug Administration has announced.

This is the second drug approved by the FDA for this indication in the past 2 years; the first was vandetanib (Caprelsa), approved in April 2011. Before these approvals, "patients with this rare and difficult to treat disease had limited therapeutic treatment options," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in the FDA’s Nov. 29 statement announcing the approval.

Cabozantinib will be marketed as Cometriq by Exelixis Inc. The recommended dose is 140 mg orally, without food (people taking the drug should not eat for at least 2 hours before and at least 1 hour after taking it). Exelixis is planning to make the drug available in late January, at an average wholesale price of $9,900 for a 28-day supply, according to the company.

In the EXAM study of 330 patients with metastatic medullary thyroid cancer, with evidence of actively progressive disease within 14 months of enrollment, the median progression-free survival was 11.2 months among those treated with cabozantinib, compared with 4 months among those on placebo, a statistically significant difference, according to the prescribing information. Partial responses were observed among 27% of those on cabozantinib but none of those on placebo, and the median duration of the objective response was 14.7 months among those on cabozantinib. At the planned interim analysis, there was no statistically significant difference in overall survival between the two groups.

The most common adverse events, reported in at least 25% of patients treated with cabozantinib, were diarrhea; stomatitis, palmar-plantar erythrodysesthesia syndrome; decreases in weight and appetite; nausea; fatigue; oral pain; hair color changes; dysgeusia; hypertension; abdominal pain; and constipation. The most common laboratory abnormalities, reported in at least 25% of patients, were increased AST, increased ALT, lymphopenia, increased alkaline phosphatase, hypocalcemia, neutropenia, thrombocytopenia, hypophosphatemia, and hyperbilirubinemia.

The prescribing information includes a boxed warning about severe and sometimes fatal hemorrhage (3%), and gastrointestinal perforations (3%) and fistulas (1%) were reported in patients treated with the drug.

The review of this drug was a priority review, completed in 6 months, which is used for drugs "that may offer major advances in treatment or that provide a treatment when no adequate therapy exists," the FDA statement said. The drug has also been designated an orphan drug, because medullary thyroid cancer is considered a rare disease.

As part of its postmarketing commitments, the FDA has requested that the company submit the final overall survival results of the study, expected to be submitted in December 2014, according to the agency’s approval letter. The letter also lists other postmarketing commitments, including the completion of a study comparing the approved dose of "a biologically active and potentially safer lower daily cabozantinib dose" in patients with progressive medullary thyroid cancer.

Cabozantinib is a kinase inhibitor that inhibits the activity of RET, MET, and other tyrosine kinases, which "are involved in both normal cellular function, and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment," according to the Exelixis statement announcing approval

The company also announced on Nov. 29 that the application for approval of cabozantinib, also based on the EXAM study, has been accepted by the European Medicines Agency for approval in the European Union.

The FDA statement cites estimates from the National Cancer Institute that 56,460 people will be diagnosed with thyroid cancer this year in the United States, and 1,780 will die from the disease, and about 4% percent of thyroid cancers are medullary thyroid cancer.

The drug’s label is available on the FDA website. Serious adverse events associated with the drug should be reported to the FDA’s MedWatch site or at 800-332-1088.

Cabozantinib, a kinase inhibitor, has been approved for the treatment of progressive, metastatic medullary thyroid cancer, on the basis of the results of an international study of 330 patients, the Food and Drug Administration has announced.

This is the second drug approved by the FDA for this indication in the past 2 years; the first was vandetanib (Caprelsa), approved in April 2011. Before these approvals, "patients with this rare and difficult to treat disease had limited therapeutic treatment options," Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in the FDA’s Nov. 29 statement announcing the approval.

Cabozantinib will be marketed as Cometriq by Exelixis Inc. The recommended dose is 140 mg orally, without food (people taking the drug should not eat for at least 2 hours before and at least 1 hour after taking it). Exelixis is planning to make the drug available in late January, at an average wholesale price of $9,900 for a 28-day supply, according to the company.

In the EXAM study of 330 patients with metastatic medullary thyroid cancer, with evidence of actively progressive disease within 14 months of enrollment, the median progression-free survival was 11.2 months among those treated with cabozantinib, compared with 4 months among those on placebo, a statistically significant difference, according to the prescribing information. Partial responses were observed among 27% of those on cabozantinib but none of those on placebo, and the median duration of the objective response was 14.7 months among those on cabozantinib. At the planned interim analysis, there was no statistically significant difference in overall survival between the two groups.

The most common adverse events, reported in at least 25% of patients treated with cabozantinib, were diarrhea; stomatitis, palmar-plantar erythrodysesthesia syndrome; decreases in weight and appetite; nausea; fatigue; oral pain; hair color changes; dysgeusia; hypertension; abdominal pain; and constipation. The most common laboratory abnormalities, reported in at least 25% of patients, were increased AST, increased ALT, lymphopenia, increased alkaline phosphatase, hypocalcemia, neutropenia, thrombocytopenia, hypophosphatemia, and hyperbilirubinemia.

The prescribing information includes a boxed warning about severe and sometimes fatal hemorrhage (3%), and gastrointestinal perforations (3%) and fistulas (1%) were reported in patients treated with the drug.

The review of this drug was a priority review, completed in 6 months, which is used for drugs "that may offer major advances in treatment or that provide a treatment when no adequate therapy exists," the FDA statement said. The drug has also been designated an orphan drug, because medullary thyroid cancer is considered a rare disease.

As part of its postmarketing commitments, the FDA has requested that the company submit the final overall survival results of the study, expected to be submitted in December 2014, according to the agency’s approval letter. The letter also lists other postmarketing commitments, including the completion of a study comparing the approved dose of "a biologically active and potentially safer lower daily cabozantinib dose" in patients with progressive medullary thyroid cancer.

Cabozantinib is a kinase inhibitor that inhibits the activity of RET, MET, and other tyrosine kinases, which "are involved in both normal cellular function, and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment," according to the Exelixis statement announcing approval

The company also announced on Nov. 29 that the application for approval of cabozantinib, also based on the EXAM study, has been accepted by the European Medicines Agency for approval in the European Union.

The FDA statement cites estimates from the National Cancer Institute that 56,460 people will be diagnosed with thyroid cancer this year in the United States, and 1,780 will die from the disease, and about 4% percent of thyroid cancers are medullary thyroid cancer.

The drug’s label is available on the FDA website. Serious adverse events associated with the drug should be reported to the FDA’s MedWatch site or at 800-332-1088.

BOSTON – An oral rinse solution of the antidepressant doxepin provided modest relief of pain from cancer treatment–induced oral mucositis in a randomized phase III trial.

Patients with head and neck cancer had a mean reduction of about two points on a 0-10 pain scale 30 minutes after using a doxepin rinse, compared with an approximate one-point reduction for patients who rinsed with a placebo (P = .0003), investigators reported at the annual meeting of the American Society for Radiation Oncology (ASTRO).

All patients in the trial had been treated with radiation with or without chemotherapy.

"Doxepin was used solely for pain relief. We did not expect it to reduce or prevent mucositis, but merely [to] treat the patients’ pain symptoms," said Dr. Robert C. Miller, a radiation oncologist at the Mayo Clinic in Rochester, Minn.

He added that "the efficacy of doxepin in treating oral mucositis pain caused by chemotherapy alone, by stem cell transplantation, or benign conditions such as aphthous ulcers warrants further study."

Conclusion Called Premature

Dr. Paul M. Harari, professor and chairman of human oncology at the University of Wisconsin, Madison, the invited discussant, agreed that oral mucositis "is a very real entity, one that impacts both patients and health care providers."

He applauded the trial’s multicenter, randomized design but noted that the overall reduction in mucositis pain with doxepin was modest, only one point better than placebo, and that mucositis pain is only one element of a host of acute and late toxicities of radiation and chemotherapy for patients with head and neck cancer.

He also said that the authors’ conclusion that "this study provides a new standard of treatment of radiotherapy-induced oral mucositis" is premature and warrants closer scrutiny.

"I would just caution for careful thought and further study before we introduce a new class of agents into the context of agents that head and neck cancer patients receive," he said. "Is this the most effective way to lower the pain score by one point in a transient measure?"

Antidepressant and Antihistamine

Doxepin is a tricyclic antidepressant with antihistaminic properties, approved in the United States for treatment of depression and anxiety as well as moderate pruritus. Preliminary data from a 2007 study suggested that doxepin could reduce mucositis pain in cancer patients (J. Pain Symptom Manage. 2007;33:111-4).

In the current study, patients with radiation to the head and neck, with or without chemotherapy and oral mucositis pain of four or greater on a 10-point pain assessment scale were enrolled. Patients received definitive radiotherapy with doses of at least 50 Gy involving more than 30% of the oral cavity.

The patients were randomized on day 1 in a double-blinded fashion to use either a single dose of either placebo or doxepin 25 mg in a 5-mL rinse and gargle, which they spat out after 1 minute. The trial had a crossover phase on day 2, with optional continuation of the active agent at the end of the study.

Participants filled out pain assessment questionnaires at baseline, four times in the first hour after rinse (in clinic), and then at 2 and 4 hours at home. Those who opted to continue doxepin filled out weekly questionnaires. Patients also were allowed to take analgesics 1 hour before or after doxepin.

A total of 140 patients (69 in the doxepin group, 71 on placebo) were available for the primary end point, total pain reduction as calculated by average mouth and throat pain area-under-the-curve (AUC) reduction over time. The AUC reduction was –9.1 among patients on doxepin, compared with –4.7 for those on placebo (P = .0003), Dr. Miller reported.

However, in 129 patients available for secondary end point analysis, doxepin, which has a known sedative effect, was associated with significantly more mean drowsiness over time (P = .03). Patients on doxepin also reported temporary unpleasant taste in the mouth, burning, and stinging, he said.

Asked whether they would continue doxepin after the randomized phase, 64% said yes and 36% declined (P = .002).

In a crossover analysis comparing the effects of doxepin and placebo in each patient, doxepin was seen to generate a benefit whether it was given before or after placebo (P less than .0001), he noted.

The study was conducted through the Alliance for Clinical Trials in Oncology and supported by a grant from the North Central Cancer Treatment Group and Mayo Clinic. Dr. Miller disclosed serving on the scientific advisory board of Tekcapital Ltd. Dr. Harari disclosed receiving research grants from the National Cancer Institute, Genentech, and Symphogen.

BOSTON – An oral rinse solution of the antidepressant doxepin provided modest relief of pain from cancer treatment–induced oral mucositis in a randomized phase III trial.

Patients with head and neck cancer had a mean reduction of about two points on a 0-10 pain scale 30 minutes after using a doxepin rinse, compared with an approximate one-point reduction for patients who rinsed with a placebo (P = .0003), investigators reported at the annual meeting of the American Society for Radiation Oncology (ASTRO).

All patients in the trial had been treated with radiation with or without chemotherapy.

"Doxepin was used solely for pain relief. We did not expect it to reduce or prevent mucositis, but merely [to] treat the patients’ pain symptoms," said Dr. Robert C. Miller, a radiation oncologist at the Mayo Clinic in Rochester, Minn.

He added that "the efficacy of doxepin in treating oral mucositis pain caused by chemotherapy alone, by stem cell transplantation, or benign conditions such as aphthous ulcers warrants further study."

Conclusion Called Premature

Dr. Paul M. Harari, professor and chairman of human oncology at the University of Wisconsin, Madison, the invited discussant, agreed that oral mucositis "is a very real entity, one that impacts both patients and health care providers."

He applauded the trial’s multicenter, randomized design but noted that the overall reduction in mucositis pain with doxepin was modest, only one point better than placebo, and that mucositis pain is only one element of a host of acute and late toxicities of radiation and chemotherapy for patients with head and neck cancer.

He also said that the authors’ conclusion that "this study provides a new standard of treatment of radiotherapy-induced oral mucositis" is premature and warrants closer scrutiny.

"I would just caution for careful thought and further study before we introduce a new class of agents into the context of agents that head and neck cancer patients receive," he said. "Is this the most effective way to lower the pain score by one point in a transient measure?"

Antidepressant and Antihistamine

Doxepin is a tricyclic antidepressant with antihistaminic properties, approved in the United States for treatment of depression and anxiety as well as moderate pruritus. Preliminary data from a 2007 study suggested that doxepin could reduce mucositis pain in cancer patients (J. Pain Symptom Manage. 2007;33:111-4).

In the current study, patients with radiation to the head and neck, with or without chemotherapy and oral mucositis pain of four or greater on a 10-point pain assessment scale were enrolled. Patients received definitive radiotherapy with doses of at least 50 Gy involving more than 30% of the oral cavity.

The patients were randomized on day 1 in a double-blinded fashion to use either a single dose of either placebo or doxepin 25 mg in a 5-mL rinse and gargle, which they spat out after 1 minute. The trial had a crossover phase on day 2, with optional continuation of the active agent at the end of the study.

Participants filled out pain assessment questionnaires at baseline, four times in the first hour after rinse (in clinic), and then at 2 and 4 hours at home. Those who opted to continue doxepin filled out weekly questionnaires. Patients also were allowed to take analgesics 1 hour before or after doxepin.

A total of 140 patients (69 in the doxepin group, 71 on placebo) were available for the primary end point, total pain reduction as calculated by average mouth and throat pain area-under-the-curve (AUC) reduction over time. The AUC reduction was –9.1 among patients on doxepin, compared with –4.7 for those on placebo (P = .0003), Dr. Miller reported.

However, in 129 patients available for secondary end point analysis, doxepin, which has a known sedative effect, was associated with significantly more mean drowsiness over time (P = .03). Patients on doxepin also reported temporary unpleasant taste in the mouth, burning, and stinging, he said.

Asked whether they would continue doxepin after the randomized phase, 64% said yes and 36% declined (P = .002).

In a crossover analysis comparing the effects of doxepin and placebo in each patient, doxepin was seen to generate a benefit whether it was given before or after placebo (P less than .0001), he noted.

The study was conducted through the Alliance for Clinical Trials in Oncology and supported by a grant from the North Central Cancer Treatment Group and Mayo Clinic. Dr. Miller disclosed serving on the scientific advisory board of Tekcapital Ltd. Dr. Harari disclosed receiving research grants from the National Cancer Institute, Genentech, and Symphogen.

BOSTON – An oral rinse solution of the antidepressant doxepin provided modest relief of pain from cancer treatment–induced oral mucositis in a randomized phase III trial.

Patients with head and neck cancer had a mean reduction of about two points on a 0-10 pain scale 30 minutes after using a doxepin rinse, compared with an approximate one-point reduction for patients who rinsed with a placebo (P = .0003), investigators reported at the annual meeting of the American Society for Radiation Oncology (ASTRO).

All patients in the trial had been treated with radiation with or without chemotherapy.

"Doxepin was used solely for pain relief. We did not expect it to reduce or prevent mucositis, but merely [to] treat the patients’ pain symptoms," said Dr. Robert C. Miller, a radiation oncologist at the Mayo Clinic in Rochester, Minn.

He added that "the efficacy of doxepin in treating oral mucositis pain caused by chemotherapy alone, by stem cell transplantation, or benign conditions such as aphthous ulcers warrants further study."

Conclusion Called Premature

Dr. Paul M. Harari, professor and chairman of human oncology at the University of Wisconsin, Madison, the invited discussant, agreed that oral mucositis "is a very real entity, one that impacts both patients and health care providers."

He applauded the trial’s multicenter, randomized design but noted that the overall reduction in mucositis pain with doxepin was modest, only one point better than placebo, and that mucositis pain is only one element of a host of acute and late toxicities of radiation and chemotherapy for patients with head and neck cancer.

He also said that the authors’ conclusion that "this study provides a new standard of treatment of radiotherapy-induced oral mucositis" is premature and warrants closer scrutiny.

"I would just caution for careful thought and further study before we introduce a new class of agents into the context of agents that head and neck cancer patients receive," he said. "Is this the most effective way to lower the pain score by one point in a transient measure?"

Antidepressant and Antihistamine

Doxepin is a tricyclic antidepressant with antihistaminic properties, approved in the United States for treatment of depression and anxiety as well as moderate pruritus. Preliminary data from a 2007 study suggested that doxepin could reduce mucositis pain in cancer patients (J. Pain Symptom Manage. 2007;33:111-4).

In the current study, patients with radiation to the head and neck, with or without chemotherapy and oral mucositis pain of four or greater on a 10-point pain assessment scale were enrolled. Patients received definitive radiotherapy with doses of at least 50 Gy involving more than 30% of the oral cavity.

The patients were randomized on day 1 in a double-blinded fashion to use either a single dose of either placebo or doxepin 25 mg in a 5-mL rinse and gargle, which they spat out after 1 minute. The trial had a crossover phase on day 2, with optional continuation of the active agent at the end of the study.

Participants filled out pain assessment questionnaires at baseline, four times in the first hour after rinse (in clinic), and then at 2 and 4 hours at home. Those who opted to continue doxepin filled out weekly questionnaires. Patients also were allowed to take analgesics 1 hour before or after doxepin.

A total of 140 patients (69 in the doxepin group, 71 on placebo) were available for the primary end point, total pain reduction as calculated by average mouth and throat pain area-under-the-curve (AUC) reduction over time. The AUC reduction was –9.1 among patients on doxepin, compared with –4.7 for those on placebo (P = .0003), Dr. Miller reported.

However, in 129 patients available for secondary end point analysis, doxepin, which has a known sedative effect, was associated with significantly more mean drowsiness over time (P = .03). Patients on doxepin also reported temporary unpleasant taste in the mouth, burning, and stinging, he said.

Asked whether they would continue doxepin after the randomized phase, 64% said yes and 36% declined (P = .002).

In a crossover analysis comparing the effects of doxepin and placebo in each patient, doxepin was seen to generate a benefit whether it was given before or after placebo (P less than .0001), he noted.

The study was conducted through the Alliance for Clinical Trials in Oncology and supported by a grant from the North Central Cancer Treatment Group and Mayo Clinic. Dr. Miller disclosed serving on the scientific advisory board of Tekcapital Ltd. Dr. Harari disclosed receiving research grants from the National Cancer Institute, Genentech, and Symphogen.