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Risk of pruritus in cancer patients treated with cetuximab: A systematic review of the literature and metaanalysis
P6060
P6967
Retrospective analysis of management of patients with hyperhidrosis in a general dermatology clinic over a 6-year period Murtaza Khan, MBBS, University Hospital Coventry and Warwickshire NHS Trust, Coventry, United Kingdom; Joanna Gach, University Hospital Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
Risk of pruritus in cancer patients treated with cetuximab: A systematic review of the literature and metaanalysis Alyx Rosen, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Courtney Ensslin, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Mario Lacouture, MD, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Shenhong Wu, MD, PhD, Stony Brook University Cancer Center, Stonybrook, NY, United States Background: Cetuximab is a monoclonal antibody that blocks the epidermal growth factor receptor. It is approved for the treatment of metastatic colorectal cancer and locally advanced or recurrent squamous cell carcinoma of the head and neck. Its use may be hindered because of dermatologic adverse events, including pruritus. Whereas rash has been reported, the incidence and risk of pruritus varies widely and has not been investigated. Therefore, we conducted a systematic review of the literature and performed a metaanalysis to determine the incidence and risk of developing pruritus in patients treated with cetuximab. Methods: Databases from PubMed and Web of Science from January 1998 until July 2012 and abstracts presented at the American Society of Clinical Oncology annual meetings from 2004 through 2012 were searched to identify relevant studies. The incidence and relative risk (RR) of pruritus was calculated using random effects or fixed effects model depending on the heterogeneity of included studies. Results: Of 224 studies identified, 6 (2.7%) reported pruritus. A total of 217 patients from these 6 clinical trials were included in this analysis. Patients with squamous cell (n ¼ 36), bronchioalveolar (n ¼ 68), hepatocellular (n ¼ 30), esophageal or gastric (n ¼ 35), nonesmall cell lung (n ¼ 18), and salivary gland carcinoma (n ¼ 30) were analyzed. The overall incidence of all-grade pruritus was 18.2% (95% confidence interval [CI], 10.8-28.8%), with a RR of 2.715 (95% CI, 1.4-5.2; P \.003).
We analyzed data collected for 57 consecutive patients referred with hyperhidrosis over a 6-year period (2005-2011). There were 39 males and 18 females. The ages at referral ranged from 4 to 57 years and duration of disease varied from 1 month to 9 years. The main sites involved were axillae in 27, hands and feet in 12, multiple sites in 9, palms only in 3, trunk in 3, face in 2, and feet in 1 patient. Aggravating factors were anxiety in 8 patients, heat in 5, exercise in 2, and food in 2. Existing anxiety or depression was reported in 6 patients; endocrinopathies including hypothyroidism, hypoparathyroidism, parathyroid adenoma, and diabetes in 5 and cervical disc disease in 1 patient. Family history of hyperhidrosis was recorded in 15% of cases. 17 patients were employed and 19 were students. Concomitant drugs included contraceptive pills in 12 patients, antidepressants 6, thyroxine 2, and others in 4. Effects on personal life or work were reported by 39 (68%) patients with soaked or damaged clothes in 14, social embarrassment 9, difficulty with writing and paperwork 9, bad odor 3, difficulty wearing shoes 2, and problems with manual work in 2. Treatments before referral included topical aluminum salts (31), propranolol (2), and glycopyrrolate cream (1). Blood tests including TSH were performed in 73% of patients and 1 showed a raised TSH. Therapies by dermatologists included aluminum salts for 18 patients, Botox injections 15, iontophoresis 14, systemic anticholinergics 10, glycopyrrolate cream 10, propranolol 4, clonidine 1, and formaldehyde soaks for 1. Sympathectomy was arranged for 2 patients and 2 were advised to stop antidepressants. 16 (28%) patients were treated with multiple modalities. Reported side effects were irritation from aluminum salts (3 patients), dry mouth (3), or palpitations (1) with anticholinergics and headache with propranolol (1). Response to treatment was documented in 23 (40%) patients. Reasons for absent documentation of response were discharge after the first treatment, failure to attend appointments, or lack of a record on treatment charts. In conclusion hyperhidrosis can have a significant impact on quality of life (QoL) of patients, but it is not routinely documented. Side effects from treatments offered were infrequent, and routine investigations were rarely useful. We would recommend regular use of standardised QoL questionnaires to help to document the response to treatments.
Conclusion: There is an increased risk of developing pruritus in cancer patients receiving cetuximab. The impact of pruritus on quality of life is significant, and is likely underreported in clinical trials. Prophylactic and early intervention against pruritus will likely improve symptomatology and patient-reported quality of life, as well as prevent suboptimal dosing. Commercial support: None identified.
Commercial support: None identified.
P7000
P6501 Review of cases presented to a drug eruption clinic at a tertiary dermatology centre in Singapore Yik Weng Yew, MBBS, National Skin Centre, Singapore; Yen Loo Lim, MBBS, National Skin Centre, Singapore Background: Unevaluated self-reported adverse drug reactions may lead to prescription of less effective or more expensive alternative drugs. A systematic work-up for suspected drug allergies/hypersensivities has been shown in some studies to provide clear cut recommendations up to 82% of patients with suspected drug allergies/hypersensivities. We aim to review the type of cases referred to a drug eruption clinic at a local tertiary dermatology centre as well as their outcomes after a systematic evaluation. Methods: We retrospectively reviewed all patients referred to and seen at an outpatient drug eruption clinic from January 2010 to September 2011 using an electronic database. Information including demographics, suspected drugs, evaluation tests, and results as well as outcome of evaluation was collected and analyzed using statistical software, SPSS 15.0 for Windows. Results: A total of 248 patients presented to the drug eruption clinic for evaluation of adverse drug reactions during the study period. Their age ranged from 1 to 91 years old with a median age of 46.5 years. There was equal gender distribution. An average of 1.5 drugs were evaluated per patient. Each patient required an average of 2 visits to the drug eruption clinic with a median follow-up duration of 1 month. More than half (52.4%) of the suspected culprit drugs were antibiotics, while 12.1% of them were nonsteroidal antiinflammatory drugs (NSAIDs). Three most common types of cutaneous drug reactions were maculopapular rash, urticaria, and angioedema. 54.4% of patients were evaluated with in vitro tests, skin tests, or drug provocation tests. 56.2% of patients had a definite outcome and recommendation after a full evaluation. Conclusion: A systematic evaluation at a drug eruption clinic is useful to patients with suspected drug allergies/hypersensitivities. Common suspected culprit drug groups, such as antibiotics and NSAIDs, are commonly prescribed and useful medications. More than half of patients with suspected allergies to these medications have a definite recommendation regarding future tolerability or avoidance of certain drugs as well as advice for alternative medications. Commercial support: None identified.
APRIL 2013
Risk of pruritus in cancer patients treated with inhibitors of the mammalian target of rapamycin, everolimus and temsirolimus: A systematic review of the literature and metaanalysis Courtney Ensslin, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Alyx Rosen, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Mario Lacouture, MD, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Shenhong Wu, MD, PhD, Stony Brook University Cancer Center, Stony Brook, NY, United States Background: Everolimus and temsirolimus, specific inhibitors of the mammalian target of rapamycin (mTOR) kinase, have emerged as effective therapies for numerous cancers. Whereas rash has been reported to mTOR inhibitors, the overall incidence of pruritus varies widely, and the risk to develop this event has not been systematically ascertained. Pruritus is a common complication of cancer treatments that negatively affects quality of life. We conducted a systematic review of the literature and performed a metaanalysis to determine the risk of pruritus among patients receiving everolimus or temsirolimus. Methods: Databases from PubMed and Web of Science from January 1998 until July 2012 and abstracts presented at the American Society of Clinical Oncology annual meetings from 2004 through 2012 were searched to identify relevant studies. The incidence and relative risk (RR) of pruritus were calculated using random effects or fixed effects model depending on the heterogeneity of included studies. Results: Studies in patients with kidney (n ¼ 63), lymphoma (n ¼ 19), endometrial (n ¼ 15), pancreatic (n ¼ 14), gastric (n ¼ 10), neuroendocrine (n ¼ 9), and head and neck squamous cell (n ¼ 1) cancers reported pruritus. Of 74 identified studies with everolimus, a total of 451 patients from 4 clinical trials were included in this analysis. The overall incidence of all-grade pruritus was 14.1% (95% confidence interval [CI], 11.1-17.6%). Conversely, of 35 identified studies with temsirolimus, a total of 186 patients from 4 clinical trials were included in this analysis. The overall incidence of all-grade pruritus was 37.7% (95% CI, 20.9-58.0%). There was a significant difference between everolimus and temsirolimus in the risk of all-grade pruritus (P\.001). Both mTOR inhibitors significantly increased the risk of all-grade pruritus in comparison with a placebo (RR for everolimus, 1.91 [95% CI, 1.01-3.63; P ¼ .047]; RR for temsirolimus, 5.01 [95% CI, 2.68-9.37; P # .001]). Conclusion: There is a significant risk of developing pruritus in cancer patients receiving mTOR inhibitors. In order to prevent suboptimal dosing and significant reduction in quality of life, patients receiving everolimus and temsirolimus should be treated against this disabling event. Commercial support: None identified.
J AM ACAD DERMATOL
AB61
P6967
Retrospective analysis of management of patients with hyperhidrosis in a general dermatology clinic over a 6-year period Murtaza Khan, MBBS, University Hospital Coventry and Warwickshire NHS Trust, Coventry, United Kingdom; Joanna Gach, University Hospital Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
Risk of pruritus in cancer patients treated with cetuximab: A systematic review of the literature and metaanalysis Alyx Rosen, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Courtney Ensslin, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Mario Lacouture, MD, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Shenhong Wu, MD, PhD, Stony Brook University Cancer Center, Stonybrook, NY, United States Background: Cetuximab is a monoclonal antibody that blocks the epidermal growth factor receptor. It is approved for the treatment of metastatic colorectal cancer and locally advanced or recurrent squamous cell carcinoma of the head and neck. Its use may be hindered because of dermatologic adverse events, including pruritus. Whereas rash has been reported, the incidence and risk of pruritus varies widely and has not been investigated. Therefore, we conducted a systematic review of the literature and performed a metaanalysis to determine the incidence and risk of developing pruritus in patients treated with cetuximab. Methods: Databases from PubMed and Web of Science from January 1998 until July 2012 and abstracts presented at the American Society of Clinical Oncology annual meetings from 2004 through 2012 were searched to identify relevant studies. The incidence and relative risk (RR) of pruritus was calculated using random effects or fixed effects model depending on the heterogeneity of included studies. Results: Of 224 studies identified, 6 (2.7%) reported pruritus. A total of 217 patients from these 6 clinical trials were included in this analysis. Patients with squamous cell (n ¼ 36), bronchioalveolar (n ¼ 68), hepatocellular (n ¼ 30), esophageal or gastric (n ¼ 35), nonesmall cell lung (n ¼ 18), and salivary gland carcinoma (n ¼ 30) were analyzed. The overall incidence of all-grade pruritus was 18.2% (95% confidence interval [CI], 10.8-28.8%), with a RR of 2.715 (95% CI, 1.4-5.2; P \.003).
We analyzed data collected for 57 consecutive patients referred with hyperhidrosis over a 6-year period (2005-2011). There were 39 males and 18 females. The ages at referral ranged from 4 to 57 years and duration of disease varied from 1 month to 9 years. The main sites involved were axillae in 27, hands and feet in 12, multiple sites in 9, palms only in 3, trunk in 3, face in 2, and feet in 1 patient. Aggravating factors were anxiety in 8 patients, heat in 5, exercise in 2, and food in 2. Existing anxiety or depression was reported in 6 patients; endocrinopathies including hypothyroidism, hypoparathyroidism, parathyroid adenoma, and diabetes in 5 and cervical disc disease in 1 patient. Family history of hyperhidrosis was recorded in 15% of cases. 17 patients were employed and 19 were students. Concomitant drugs included contraceptive pills in 12 patients, antidepressants 6, thyroxine 2, and others in 4. Effects on personal life or work were reported by 39 (68%) patients with soaked or damaged clothes in 14, social embarrassment 9, difficulty with writing and paperwork 9, bad odor 3, difficulty wearing shoes 2, and problems with manual work in 2. Treatments before referral included topical aluminum salts (31), propranolol (2), and glycopyrrolate cream (1). Blood tests including TSH were performed in 73% of patients and 1 showed a raised TSH. Therapies by dermatologists included aluminum salts for 18 patients, Botox injections 15, iontophoresis 14, systemic anticholinergics 10, glycopyrrolate cream 10, propranolol 4, clonidine 1, and formaldehyde soaks for 1. Sympathectomy was arranged for 2 patients and 2 were advised to stop antidepressants. 16 (28%) patients were treated with multiple modalities. Reported side effects were irritation from aluminum salts (3 patients), dry mouth (3), or palpitations (1) with anticholinergics and headache with propranolol (1). Response to treatment was documented in 23 (40%) patients. Reasons for absent documentation of response were discharge after the first treatment, failure to attend appointments, or lack of a record on treatment charts. In conclusion hyperhidrosis can have a significant impact on quality of life (QoL) of patients, but it is not routinely documented. Side effects from treatments offered were infrequent, and routine investigations were rarely useful. We would recommend regular use of standardised QoL questionnaires to help to document the response to treatments.
Conclusion: There is an increased risk of developing pruritus in cancer patients receiving cetuximab. The impact of pruritus on quality of life is significant, and is likely underreported in clinical trials. Prophylactic and early intervention against pruritus will likely improve symptomatology and patient-reported quality of life, as well as prevent suboptimal dosing. Commercial support: None identified.
Commercial support: None identified.
P7000
P6501 Review of cases presented to a drug eruption clinic at a tertiary dermatology centre in Singapore Yik Weng Yew, MBBS, National Skin Centre, Singapore; Yen Loo Lim, MBBS, National Skin Centre, Singapore Background: Unevaluated self-reported adverse drug reactions may lead to prescription of less effective or more expensive alternative drugs. A systematic work-up for suspected drug allergies/hypersensivities has been shown in some studies to provide clear cut recommendations up to 82% of patients with suspected drug allergies/hypersensivities. We aim to review the type of cases referred to a drug eruption clinic at a local tertiary dermatology centre as well as their outcomes after a systematic evaluation. Methods: We retrospectively reviewed all patients referred to and seen at an outpatient drug eruption clinic from January 2010 to September 2011 using an electronic database. Information including demographics, suspected drugs, evaluation tests, and results as well as outcome of evaluation was collected and analyzed using statistical software, SPSS 15.0 for Windows. Results: A total of 248 patients presented to the drug eruption clinic for evaluation of adverse drug reactions during the study period. Their age ranged from 1 to 91 years old with a median age of 46.5 years. There was equal gender distribution. An average of 1.5 drugs were evaluated per patient. Each patient required an average of 2 visits to the drug eruption clinic with a median follow-up duration of 1 month. More than half (52.4%) of the suspected culprit drugs were antibiotics, while 12.1% of them were nonsteroidal antiinflammatory drugs (NSAIDs). Three most common types of cutaneous drug reactions were maculopapular rash, urticaria, and angioedema. 54.4% of patients were evaluated with in vitro tests, skin tests, or drug provocation tests. 56.2% of patients had a definite outcome and recommendation after a full evaluation. Conclusion: A systematic evaluation at a drug eruption clinic is useful to patients with suspected drug allergies/hypersensitivities. Common suspected culprit drug groups, such as antibiotics and NSAIDs, are commonly prescribed and useful medications. More than half of patients with suspected allergies to these medications have a definite recommendation regarding future tolerability or avoidance of certain drugs as well as advice for alternative medications. Commercial support: None identified.
APRIL 2013
Risk of pruritus in cancer patients treated with inhibitors of the mammalian target of rapamycin, everolimus and temsirolimus: A systematic review of the literature and metaanalysis Courtney Ensslin, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Alyx Rosen, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Mario Lacouture, MD, Memorial Sloan-Kettering Cancer Center, New York, NY, United States; Shenhong Wu, MD, PhD, Stony Brook University Cancer Center, Stony Brook, NY, United States Background: Everolimus and temsirolimus, specific inhibitors of the mammalian target of rapamycin (mTOR) kinase, have emerged as effective therapies for numerous cancers. Whereas rash has been reported to mTOR inhibitors, the overall incidence of pruritus varies widely, and the risk to develop this event has not been systematically ascertained. Pruritus is a common complication of cancer treatments that negatively affects quality of life. We conducted a systematic review of the literature and performed a metaanalysis to determine the risk of pruritus among patients receiving everolimus or temsirolimus. Methods: Databases from PubMed and Web of Science from January 1998 until July 2012 and abstracts presented at the American Society of Clinical Oncology annual meetings from 2004 through 2012 were searched to identify relevant studies. The incidence and relative risk (RR) of pruritus were calculated using random effects or fixed effects model depending on the heterogeneity of included studies. Results: Studies in patients with kidney (n ¼ 63), lymphoma (n ¼ 19), endometrial (n ¼ 15), pancreatic (n ¼ 14), gastric (n ¼ 10), neuroendocrine (n ¼ 9), and head and neck squamous cell (n ¼ 1) cancers reported pruritus. Of 74 identified studies with everolimus, a total of 451 patients from 4 clinical trials were included in this analysis. The overall incidence of all-grade pruritus was 14.1% (95% confidence interval [CI], 11.1-17.6%). Conversely, of 35 identified studies with temsirolimus, a total of 186 patients from 4 clinical trials were included in this analysis. The overall incidence of all-grade pruritus was 37.7% (95% CI, 20.9-58.0%). There was a significant difference between everolimus and temsirolimus in the risk of all-grade pruritus (P\.001). Both mTOR inhibitors significantly increased the risk of all-grade pruritus in comparison with a placebo (RR for everolimus, 1.91 [95% CI, 1.01-3.63; P ¼ .047]; RR for temsirolimus, 5.01 [95% CI, 2.68-9.37; P # .001]). Conclusion: There is a significant risk of developing pruritus in cancer patients receiving mTOR inhibitors. In order to prevent suboptimal dosing and significant reduction in quality of life, patients receiving everolimus and temsirolimus should be treated against this disabling event. Commercial support: None identified.
J AM ACAD DERMATOL
AB61