title: Effect of concurrent medications on cisplatin-induced nephrotoxicity in patients with head and neck cancer.
abstract: The goal of this study was to identify clinical characteristics and concurrent medications associated with an increased or decreased incidence of cisplatin-induced nephrotoxicity. The medical records for 62 subjects with head and neck cancer who received cisplatin 100 mg/m2 (day 1) plus fluorouracil 1000 mg/m2 (days 1-5) with or without radiation therapy were reviewed from three medical centers. The demographics, concurrent medication therapy, co-existing illnesses and clinical laboratory values were extracted from the medical records. Nephrotoxicity was defined as a minimum rise in serum creatinine of 0.5 mg/dl or above. The concurrent use of hydrochlorothiazide or multivitamins was associated with a higher incidence of nephrotoxicity after cycle 1. Use of albuterol, atenolol or hydrochlorothiazide was also associated with a higher incidence of nephrotoxicity after cycle 1 or 2. In contrast, subjects prescribed dexamethasone or ondansetron were less likely to experience nephrotoxicity. None of these medications affected treatment response. Race/ethnicity was independently correlated with the incidence of nephrotoxicity; African-American subjects were more likely to develop nephrotoxicity independent of the influence of these concurrent medications. Medications may modulate cisplatin-induced nephrotoxicity by altering the metabolic activation of cisplatin to a nephrotoxin. Genetic differences in the drug-metabolizing enzymes may contribute to the correlation with race. The results from this retrospective study provide data to support a larger prospective study to further investigate the associations between these concurrent medications and cisplatin-induced nephrotoxicity.
authors.affiliation: Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Illinois, USA.
authors.forename: Stacy S
authors.initials: SS
authors.lastname: Shord
authors.forename: David M
authors.initials: DM
authors.lastname: Thompson
authors.forename: Greg A
authors.initials: GA
authors.lastname: Krempl
authors.forename: Marie H
authors.initials: MH
authors.lastname: Hanigan
mesh_terms: D000420:Albuterol / Q000009:adverse effects; D000959:Antihypertensive Agents / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001262:Atenolol / Q000009:adverse effects; D002945:Cisplatin / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D003710:Demography; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D006852:Hydrochlorothiazide / Q000009:adverse effects; D015994:Incidence; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D001262:Atenolol; D003404:Creatinine; D002945:Cisplatin; D000420:Albuterol; D005472:Fluorouracil