Nephrotoxicity of heptaplatin: a randomized comparison with cisplatin in advanced gastric cancer

Purpose: Heptaplatin is a newly developed platinum derivative which has been reported to be less toxic than cisplatin. This study was designed to evaluate the nephrotoxicity of heptaplatin in comparison with that of cisplatin. Methods: Previously untreated advanced gastric cancer patients with normal renal function were randomly assigned into either group I (heptaplatin 400 mg/m(2) i.v. over 1 h on day 1 plus 5-fluorouracil (5-FU) 1000 mg/m(2) per day continuous i.v. from day 1 to day 5), or group II (cisplatin 60 mg/m(2) i.v. over 1 h on day 1 plus 5-FU 1000 mg/m(2) per day continuous i.v. from day 1 to day 5), with the cycles repeated every 4 weeks. Renal function parameters before, during, and after the chemotherapy were compared between the two groups. Results: A total of 99 patients were enrolled in the study, 51 in group I and 48 in group II. The 24-h proteinuria on day 5 was markedly increased in group I (95 +/- 108 mg/day to 9098 +/- 4514 mg/day, means +/- SD) in comparison with the increase observed in group II (104 +/- 148 mg/day to 151 +/- 102 mg/day), and creatinine clearance showed a greater decrease in group I (83.1 +/- 23.6 ml/min to 44.9 +/- 17.3 ml/min) than in group II (89.6 +/- 22.1 ml/min to 72.8 +/- 21.0 ml/min). The differences in these parameters between the two groups were statistically significant throughout the subsequent cycles. Conclusions: Our findings show that nephrotoxicity was more severe in patients treated with heptaplatin 400 mg/m(2) than with cisplatin 60 mg/m(2) when it was combined with 5-FU. Measures to more effectively prevent nephrotoxicity should be developed for the safe use of heptaplatin.