Nephrotoxicity of heptaplatin: a randomized comparison with cisplatin in advanced gastric cancer.
OBJECTIVE
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.
Ahn
Jin-Hee
JH
Section of Hematology/Oncology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Korea.
Kang
Yoon-Koo
YK
Kim
Tae-Won
TW
Bahng
Haeseoung
H
Chang
Heung-Moon
HM
Kang
Wee-Chang
WC
Kim
Woo Kun
WK
Lee
Jung-Shin
JS
Park
Jung-Sik
JS
D000208:Acute Disease; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D003131:Combined Modality Therapy; D003404:Creatinine / Q000097:blood; D003907:Dexamethasone / Q000627:therapeutic use; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005743:Gastrectomy; D006801:Humans; D007262:Infusions, Intravenous; D007674:Kidney Diseases / Q000139:chemically induced*; D007677:Kidney Function Tests; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008314:Malonates / Q000008:administration & dosage / Q000009:adverse effects*; D008657:Metabolic Clearance Rate; D008787:Metoclopramide / Q000627:therapeutic use; D008875:Middle Aged; D017294:Ondansetron / Q000627:therapeutic use; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D011507:Proteinuria / Q000139:chemically induced; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control
D000932:Antiemetics; D008314:Malonates; D009944:Organoplatinum Compounds; C090717:SKI 2053R; D017294:Ondansetron; D003907:Dexamethasone; D003404:Creatinine; D008787:Metoclopramide; D002945:Cisplatin; D005472:Fluorouracil