CIS-DIAMMINEDICHLOROPLATINUM (CDDP) THERAPY FOR BRAIN METASTASIS OF LUNG-CANCER .1. 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 (IV) or intra-arterially (IA) at the time of surgery, and various fluids a nd tissues were sampled for measurement of drug concentration. Compari son of the two routes of administration disclosed that the plasma leve l was slightly lower after IA than after IV infusion, whereas there wa s no difference between the two routes in terms of drug diffusion into the brain tissue adjacent to the tumor. However, IA administration re sulted in an intratumoral drug concentration twice as high as that ach ieved with IV infusion. The tumor-:plasma and tumor: adjacent brain ra tios of drug concentration after IA injection were also twice those me asured after IV administration. The distribution pattern of CDDP is ch aracteristic of water-soluble agents. All patients experienced tolerab le nausea and vomiting. Creatinine clearance was moderately reduced in ten cases, but no serious renal toxicity was observed. Seizures occur red postoperatively in nine patients. Infrequent side effects were mye losupression, ototoxicity, and postoperative intracranial bleeding. Al l adverse effects disappeared with conservative treatment or no interv ention.