42-hour methotrexate infusions as relapse therapy for childhood malignancies: toxicity and efficacy of 109 infusions.

Thirty-six children and adolescents received 42-h methotrexate (MTX) infusions in doses of 5.5-22 g/m2 as a single drug or as part of a combination chemotherapy for relapsed childhood leukemias or solid tumors. In a total of 109 courses serum MTX concentrations were maintained at 2 x 10(-5) -2 x 10(-4) M for 42 h before leukovorin rescue was started. There were responses in one of two hemangiopericytomas, two of five Ewing's sarcomas, and six of eight rhabdomyosarcomas. In ALL, NHL, and neuroblastomas, responses were seen with 42-h MTX infusions as part of a combination chemotherapy. The major toxicities were mucositis in 45%, nausea and vomiting in 35%, and hepatic toxicity in 25% of the courses. Bone marrow depression as well as neuro- and nephrotoxicity were rare. Long-term MTX infusions in high doses are strongly recommended for the treatment of relapsed childhood malignancies because of their efficacy and mild toxicity.