Human central nervous system distribution of cis-diamminedichloroplatinum and use as a radiosensitizer in malignant brain tumors.

TLDR

The study investigated CDDP pharmacology in the CNS and initiated trials of CDDP as a radiosensitizer for malignant primary brain tumors. Platinum levels were measured by X‑ray‑dispersive fluorescence spectrometry, and treatment required close monitoring with occasional dose omissions. In 15 patients, CDDP was given weekly during cranial irradiation and at higher doses post‑irradiation; platinum was barely detectable in CSF, and treatment caused tolerable gastrointestinal, scalp, renal, hypomagnesemia, and occasional myelosuppression, with possible ototoxicity and CNS toxicity in some cases, while its impact on survival remains unassessed.

Abstract

Abstract The human central nervous system pharmacology of cis -diamminedichloroplatinum (CDDP) was studied, and trials were initiated of CDDP as a radiosensitizer in the treatment of malignant primary brain tumors. Samples were assayed for platinum using X-ray-dispersive fluorescence spectrometry. Platinum was barely detectable in cerebrospinal fluid from two patients and was not detectable ( Fifteen patients with malignant brain tumors received CDDP, 40 mg/sq m/week i.v., during cranial irradiation, and some received 105 to 120 mg/sq m every 3 weeks after cranial irradiation. Close follow-up was necessary, and some weekly treatments needed to be omitted in individual patients. During the weekly CDDP, gastrointestinal, scalp, and renal toxicities and hypomagnesemia were noted but were tolerable. Only one patient developed myelosuppression. Ototoxicity may have been enhanced. Postirradiation CDDP, 105 to 120 mg/sq m every 3 weeks, caused substantially more gastrointestinal toxicity and may have caused central nervous system toxicity in four patients, although other factors probably contributed. It is too early to evaluate effect on survival.