Pharmacokinetic study in carboplatin, cisplatin and 5-fluorouracil regimen for advanced oesophageal cancer.
A chemotherapy using carboplatin, cisplatin and 5-fluorouracil in continuous infusion for advanced oesophageal cancer showed a high response rate in a previous feasibility study. The overall CT-scan response rate of 85% was obtained with a haematological dose-limiting toxicity: neutropenia and thrombopenia grade 3-4 of 23% and 30% respectively. In order to correlate myelosuppression with pharmacokinetic parameters, a pharmacological study was undertaken. The area under curve (AUC) of ultrafiltrable platinum and the residual rate of total platinum in 16 patients were tested. The measured creatinine clearance was found to be predictive of the subsequent myelosuppression. Plasma samples were using daily using the atomic absorption spectrometry technique. A strong relationship in individual patients was underlined between the AUC of ultrafiltrable platinum or residual rate of total platinum and the lowest platelet count for the first 3 days of treatment (p < 0.05). Conversely, the threshold value of the AUC at day one and residual rate at days two and three were calculated to prevent a highly probable haematotoxicity. Therefore, an optimal dose of carboplatin is determined in relation to the renal function of each patient.
Leger-Enreille
A
A
Laboratoire de Biochimie et Pharmacocinétique, Centre Jean Perrin, Clermont Fd., France.
Cure
H
H
Pezet
D
D
Bargnoux
P J
PJ
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics*; D016190:Carboplatin / Q000008:administration & dosage / Q000493:pharmacokinetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism*; D002945:Cisplatin / Q000493:pharmacokinetics; D003404:Creatinine / Q000097:blood; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012044:Regression Analysis; D013054:Spectrophotometry, Atomic; D016896:Treatment Outcome
D003404:Creatinine; D016190:Carboplatin; D002945:Cisplatin; D005472:Fluorouracil