cis-diamminedichloroplatinum (CDDP) therapy for brain metastasis of lung cancer. I. Distribution within the central nervous system after intravenous and intracarotid infusion.

The distribution of cis-diamminedichloroplatinum (CDDP) was studied in 23 patients undergoing surgical resection of brain tumors metastatic from lung cancer. CDDP (100 mg/m2) was administered intravenously (i.v.) or intra-arterially (IA) at the time of surgery, and various fluids and tissues were sampled for measurement of drug concentration. Comparison of the two routes of administration disclosed that the plasma level was slightly lower after IA than after i.v. infusion, whereas there was no difference between the two routes in terms of drug diffusion into the brain tissue adjacent to the tumor. However, IA administration resulted in an intratumoral drug concentration twice as high as that achieved with i.v. infusion. The tumor:plasma and tumor:adjacent brain ratios of drug concentration after IA injection were also twice those measured after i.v. administration. The distribution pattern of CDDP is characteristic of water-soluble agents. All patients experienced tolerable nausea and vomiting. Creatinine clearance was moderately reduced in ten cases, but no serious renal toxicity was observed. Seizures occurred postoperatively in nine patients. Infrequent side effects were myelosuppression, ototoxicity, and postoperative intracranial bleeding. All adverse effects disappeared with conservative treatment or no intervention.