Although
cisplatin may have intrinsic activity against
astrocytoma, limited penetration into the central nervous system may severely curtail delivery of adequate amounts of
drug to the
tumor. In an attempt to increase the dose of delivered
drug without markedly increasing toxicity,
cisplatin was administered by 5-day continuous
intravenous infusion at a dose of 28 mg/m2/day (total dose 140 mg/m2) to 15 evaluable patients (5 with
astrocytoma Grade III and 10 with
astrocytoma Grade IV). Median age was 39 years, median Karnofsky Performance Status was 80%, and all patients had been previously treated with other modalities. One patient (7%) achieved Partial Response as demonstrated by increased strength of paretic extremities, increased Karnofsky Performance Status, and decrease of enhancing
tumor mass on CT scan. Although nephrotoxicity was minimal,
nausea and
vomiting (usually mild) was seen in 14 patients. Myelosuppression was also common (
anemia in 7 patients,
leukopenia in 4 patients and
thrombocytopenia in 3 patients).
Ototoxicity was seen in 5 patients and may represent a combined modality toxicity with prior cranial
radiotherapy. Routes and schedules which allow a higher peak serum concentration of
cisplatin (such as subselective intracerebral artery infusion) may be necessary to achieve greater central nervous system
drug penetration and to maximally exploit
cisplatin in the treatment of
astrocytoma.