title: Prevention of carboplatin-induced hypersensitivity reactions in women with ovarian cancer.
abstract: Background Carboplatin-based chemotherapy offers high response rates and improved overall survival for women with epithelial ovarian cancer, but its use is limited by the occurrence of hypersensitivity reactions. To evaluate the efficacy of prophylactic diphenhydramine for hypersensitivity reaction prevention, we reviewed the incidence of hypersensitivity reactions and identified patients at high risk of hypersensitivity reactions. Methods Women receiving ≥6 cycles of carboplatin-based chemotherapy for epithelial ovarian cancer were identified from our institutional database at the Princess Margaret Cancer Centre. Institutional policy was changed in 2009 to introduce diphenhydramine prophylaxis for patients receiving ≥6 cycles of carboplatin. Additional clinical data were abstracted from the patient record. Results Between 2006 and 2012, 450 women received ≥6 cycles of carboplatin-based chemotherapy for epithelial ovarian cancer. Two hundred and ninety-one women received prophylaxis with diphenhydramine. Carboplatin-induced hypersensitivity reactions occurred in 41 of 449 patients (9%). Univariable predictors of carboplatin-induced hypersensitivity reactions included administration of 8 to 10 cycles of carboplatin, history of other drug allergies and a platinum-free interval >12 months. BRCA mutational status was not predictive. In a multivariable analysis, the number of cycles of carboplatin and a platinum-free interval >12 months were independent predictors of hypersensitivity reactions. There was a trend towards diphenhydramine prophylaxis reducing the incidence of hypersensitivity reactions in women with a platinum-free interval compared to continuous delivery; this was most marked when the platinum-free interval was >12 months (n = 64) (OR: 0.2 (95% CI: 0.046-0.83), p = 0.03). Conclusions The administration of diphenhydramine to women who have a platinum-free interval may reduce the risk of hypersensitivity reaction, but prospective evaluation is required.
authors.affiliation: 1 Division of Medical Oncology and Hematology, Faculty of Medicine, University of Toronto, Sunnybrook Odette Cancer Center, Toronto, Ontario, Canada.
authors.forename: Katarzyna J
authors.initials: KJ
authors.lastname: Jerzak
authors.affiliation: 2 Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Shaidah
authors.initials: S
authors.lastname: Deghan Manshadi
authors.affiliation: 3 Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Pamela
authors.initials: P
authors.lastname: Ng
authors.affiliation: 3 Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Manjula
authors.initials: M
authors.lastname: Maganti
authors.affiliation: 3 Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Jeanna M
authors.initials: JM
authors.lastname: McCuaig
authors.affiliation: 3 Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Marcus
authors.initials: M
authors.lastname: Bulter
authors.affiliation: 3 Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
authors.forename: Amit
authors.initials: A
authors.lastname: Oza
authors.affiliation: 1 Division of Medical Oncology and Hematology, Faculty of Medicine, University of Toronto, Sunnybrook Odette Cancer Center, Toronto, Ontario, Canada.
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Mackay
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects*; D000077216:Carcinoma, Ovarian Epithelial; D004155:Diphenhydramine / Q000627:therapeutic use*; D004342:Drug Hypersensitivity / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D006634:Histamine H1 Antagonists; D004155:Diphenhydramine; D016190:Carboplatin
keywords: Hypersensitivity; carboplatin; diphenhydramine; prevention; risk factors