[Studies on the appropriate administration of cisplatin based on pharmacokinetics and toxicity]

Ninety-six patients with non-small cell lung cancer were treated with cisplatin (80-150 mg/m2). The pharmacokinetics of cisplatin were studied in 27 of these patients. Cisplatin was administered intravenously for 30-120 min. Plasma concentrations of total platinum and ultrafilterable (non-protein-bound) platinum were monitored by flameless atomic absorption spectrophotometry. Maximum total platinum levels in plasma were attained at the end of infusion, and thereafter decayed in a biphasic fashion, with an initial phase half-life (t1/2 alpha) of 10.2 to 14.6 min and a secondary phase half-life (t1/2 beta) of 41.7 to 81.3 h. The half-life was prolonged as the dosage was increased. Non-protein-bound platinum was rapidly cleared to below the measurable level within 4 hours at 80 mg/m2 and 120 mg/m2 of cisplatin, but declined in a biphasic manner, with t1/2 alpha of 31.2 min and t1/2 beta of 20.1 h at 150 mg/m2 of cisplatin. Toxicities were increased according to dosage, and decreased with a 50 mg/m2 X 3 days regime. Nephrotoxicity and ototoxicity were the dose-limiting factors in the single-dose escalation scheme used. In conclusion, the optimal dosage of cisplatin appeared to be 120 mg/m2 considering its toxicity.