The protective potential of the combination of verapamil and cimetidine on cisplatin-induced nephrotoxicity in man

✍ Scribed by D. Th. Sleijfer; J. J. G. Offerman; N. H. Mulder; M. Verweij; G. K. van der Hem; H. Schraffordt Koops; S. Meijer

• Publisher: John Wiley and Sons
• Year: 1987
• Tongue: English
• Weight: 475 KB
• Volume: 60
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/1097-0142(19871201)60:11<2823::aid-cncr2820601138>3.0.co;2-c

✦ Synopsis

Nine patients (Group A) with histologically proven, nonseminomatous testicular cancer were treated with cisplatin (CDDP) according to the Einhorn regimen. Renal function studies including the measurement of the effective renal plasma flow (ERPF) and the glomerular filtration rate (GFR) were performed prior to the chemotherapy and then after treatment on days 10 and 21 of the first course. In order to prevent CDDP-induced nephrotoxicity, verapamil (a calcium entry blocker) and cimetidine were given along with CDDP. The results were compared with others from another group of nine patients (Group B) treated with CDDP, but without verapamil and cimetidine. In Group A there was much less of a decrease in ERPF as compared to Group B on day 21. In addition, the decrease in GFR on days 10 and 21 was totally prevented in the verapamil-and cimetidine-treated group.

Cancer 60:2823-2828. 1987.

ISPLATIN (CDDD) is an antineoplastic agent fre-C quently used in the treatment of a variety of tumors. It especially improves response rates in patients with disseminated testicular and ovarian cancer. 'I'

Many side effects are k n ~w n , ~ but the dose-limiting side effect is its nephrotoxicity, expressed as an increase in the serum creatinine concentration or a decrease in creatinine ~learance.~.~

We have already reported early changes in renal function during CDDP treatment, which included a decrease in effective renal plasma flow (ERPF) and an increase in the filtration fraction, both occurring before any changes in the glomerular filtration rate (GFR) could be observed.6 In rats these findings could be confirmed by others using a different technique.' The decrease in GFR occurred later on.8 During chemotherapy, the reduction in ERPF could be an early sign of the mechanism leading to renal dysfunction. Therefore, it is sug-