The Memorial Sloan Kettering Cancer Center experience with outpatient administration of high dose methotrexate with leucovorin rescue

Background. We describe the safety and feasibility of an out-patient high dose methotrexate (HDMTX) regimen. Methods. HDMTX (12 g/m²) is administered in a pediatric day hospital (PDH) intravenously (IV) over 4 hrs. Urinary alkalinization is achieved using an IV bolus of sodium bicarbonate and oral bicarbonate tablets. Daily visits to the PDH follow. Leucovorin is begun 24 hrs. after MTX at a standard dose of 10 mg orally (po) every 6 hrs. (q6h). The leucovorin dose is escalated between a range of 20 mg po q6h to 1 g as a continuous IV drip over 24 hrs. according to an institutional algorithm for levels above 10, 1, and 0.1 μmol/L at 24, 48, and 72 hrs. post-MTX. To evaluate our approach, we conducted a retrospective review of all HDMTX courses administered at the Memorial Sloan Kettering Cancer Center between 1996 and 2002. Results. Out of a total of 708 MTX courses, 82% were successfully completed as an outpatient. Forty-nine percent of the MTX courses were treated with standard dose leucovorin while 49% required a dose escalation, the majority of which was to 20-30 mg po q6h. Observed toxicity included mild (Grade 0-1) nephrotoxicity and reversible transaminitis in the majority of patients. Myelosuppression was manifested mainly as neutropenia, with Grade III-IV toxicity in 16% of patients. Conclusions. Outpatient administration of HDMTX and the required supportive therapy is safe and feasible using the described approach. Approximately half of the patients will require leucovorin dose modification based on serial monitoring of MTX levels.