CONCENTRATION X TIME METHOTREXATE VIA A SUBCUTANEOUS RESERVOIR - LESS TOXIC REGIMEN FOR INTRA-VENTRICULAR CHEMOTHERAPY OF CENTRAL NERVOUS-SYSTEM NEOPLASMS
Neurotoxicity associated with intrathecal methotrexate therapy was shown to correlate with elevated concentrations of the drug in the CSF as well as total cumulative dosage. Nineteen patients with meningeal leukemia were randomized to receive courses of intraventricular methotrexate via an Ommaya reservoir consisting of single injections of 12 mg/m2 per dose or a low-dose concentration .times. time (C .times. T) schedule of 1 mg every 12 h for 3 days. There were no significant differences between the 2 treatment groups in the rate of remission induction, number of relapses or durations of remission. The mean (.+-. 1 SD) cumulative methotrexate dose was 66 .+-. 41 mg/m2 in the C .times. T group and 173 .+-. 64 mg/m2 in the 12 mg/m2 per dose group (P < 0.005). Neurologic toxicity occurred in 1 of 8 patients in the C .times. T group and 7 of 10 patients in the 12 mg/m2 per dose group (P < 0.05). These observations suggest that the C .times. T dosage schedule is less neurotoxic and equally effective in the treatment of CNS leukemia.