"Concentration x time" methotrexate via a subcutaneous reservoir: a less toxic regimen for intraventricular chemotherapy of central nervous system neoplasms

Neurotoxicity associated with intrathecal methotrexate therapy has been shown to correlate with elevated concentrations of the drug in the cerebrospinal fluid as well as with the total cumulative dosage. In our study 19 patients with meningeal leukemia were randomized to receive courses of intraventricular methotrexate via an Ommaya reservoir consisting of either single injections of 12 mg/sq m/dose or a low-dose “concentration x time” (C x T) schedule of 1 mg every 12 hr for 3 days. There were no significant differences between the two treatment groups in the rate of remission induction, the number of relapses, or the durations of remission. The mean (+/- 1 SD) cumulative methotrexate dose was 66 +/- 41 mg/sq m in the C x T group and 173 +/- 64 mg/sq m in the 12 mg/sq m/dose group (p less than 0.005). Neurologic toxicity occurred in one of the eight patients in the C x T group and in seven of ten patients in the 12 mg/sq m/dose group (p less than 0.05). These observations suggest that the C x T dosage schedule is less neurotoxic and equally effective in the treatment of central nervous system leukemia.