title: Increased nephrotoxicity of combination taxol and cisplatin chemotherapy in gynecologic cancers as compared to cisplatin alone.
abstract: To investigate the increased nephrotoxicity of taxol and cisplatin combination chemotherapy in gynecologic cancers as compared to cisplatin alone, the medical records of 25 patients with gynecological cancers were reviewed for evaluation of nephrotoxicity after chemotherapy treatment. The data included age, serum creatinine, calculated creatinine clearance, initial and cumulative dose of cisplatin and taxol, primary site of the cancer, renal ultrasound and hydration protocols. Renal function was evaluated before, during and 6 months after chemotherapy. Renal dysfunction was defined as a greater than 25% decrease in creatinine clearance. Comparing 11 patients treated with taxol and cisplatin versus 14 treated with cisplatin alone, there was a significant difference in effect on renal function. Nine of 11 patients (81%) treated with the combination chemotherapy had a greater than 25% decrease in creatinine clearance while only 4 of the 14 patients (29%) treated with cisplatin alone had such a decrease in creatinine clearance (p < 0.004). The patients treated with the combination chemotherapy, however, received a higher dose of cisplatin (80.4 vs. 66.4 mg/m2, p < 0.02) and were treated longer (6.7 vs. 4.3 months, p < 0.002). Nevertheless, when the patients were matched for age, initial dose and cumulative dose of cisplatin, a higher frequency of nephrotoxicity persisted in patients treated with taxol and cisplatin as compared to cisplatin alone (72 as compared to 20%, p < 0.02). The patients in both groups were comparably hydrated; prerenal failure and urinary tract obstruction were excluded in all patients. Six months after completion of chemotherapy, a significantly lower creatinine clearance was still observed in patients treated with taxol and cisplatin combination therapy (46 vs. 76 ml/min, p < 0.01). In summary, a retrospective analysis of renal function in patients with gynecological cancers showed an increased nephrotoxicity in patients treated with taxol and cisplatin as compared to cisplatin alone. A prospective study is therefore needed to examine the potential additive toxic effect of the combination of taxol and cisplatin on long-term renal function, including potential preventive interventions.
authors.affiliation: Department of Medicine, University of Colorado School of Medicine, Denver 80262, USA.
authors.forename: A
authors.initials: A
authors.lastname: Merouani
authors.forename: S A
authors.initials: SA
authors.lastname: Davidson
authors.forename: R W
authors.initials: RW
authors.lastname: Schrier
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced*; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies
chemical_list: D017239:Paclitaxel; D002945:Cisplatin