Clinical pharmacological and toxicological studies of Cis-diamminedichloroplatinum (II) by continuous intravenous infusion

Pharmacological and toxicological studies of DDP were conducted in 35 patients with solid tumors, who received a priming dose of the agent at 5 mg/m² followed by continuous i.v. infusion at 20 mg/m² daily for 5 days. DDP in biological fluids was determined either colorimetrically or by atomic absorption spectrometry. Upon cessation of infusion, the average terminal plasma t1/2 of DDP in 7 patients was 34.7 hr; however, in a patient with oliguric renal failure, it was 96 hr. During infusion, plasma DDP concentrations varied between 0.5-4.3 mg/l. The cumulative urinary excretion of DDP was 34 per cent in 8 days. In concentrations of 1-50 mg/l DDP was 26-56 per cent bound to human plasma protein at 28°. The toxicity of DDP by i.v. infusion included nausea and vomiting in 94 per cent of the patients, but of much less severity than by other schedules. Additionally, nephrotoxicity was seen in 21 per cent of the patients, and tinnitus or audiogram abnormalities in 10 per cent; hematologic toxicity was mild. Complete remission lasting more than 4 months was seen in a patient with basal cell carcinoma. Also, of 7 patients with squamous cell carcinoma of the head and neck or cervix, 3 showed partial remission and 2 showed stabilization of their disease. Continuous i.v. infusion therefore offers the advantage of attenuating the nausea and vomiting caused by DDP.