Effect of concurrent medications on cisplatin-induced nephrotoxicity in patients with head and neck cancer

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/m(2) (day 1) plus fluorouracil 1000 mg/m(2) (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.