Methotrexate as a single agent and in combination chemotherapy for the treatment of non-Hodgkin's lymphoma of unfavorable histology.

High-dose methotrexate (HDMTX) with citrovorum factor (CF) was used to treat non-Hodgkin's lymphomas either as a single agent in those patients who had previously failed to respond to conventional chemotherapy or in previously untreated patients in combination with bleomycin, Adriamycin, cytoxan, and vincristine. Twenty-five patients who had been previously treated and were refractory to cytotoxic chemotherapy were treated with HDMTX ranging between 1 and 7.5 g/m2 as an iv infusion over 20 to 40 minutes. CF rescue was begun at 24 hours and was maintained orally every 6 hours at 10 mg/m2 for a total of 72 hours. In instances where the 24-hour serum level of MTX was in excess of 1 X 10(-7) M, the dose of CF was increased to 100 mg/m2 every 3 hours until the serum MTX level fell into the appropriate range. Of the 25 patients, 13 (52%) responded. Response duration was brief, lasting a median of 2 months. Three patients had prolonged control lasting 13, 16, and 21 months respectively. Five of the six patients with central nervous system (CNS) involvement have demonstrated marked clearing of spinal fluid abnormalities and reversion of brain scans toward normal. Fifty-four previously untreated patients with diffuse histiocytic or undifferentiated lymphoma have been treated with combination chemotherapy including MTX given at the level of 3 g/m2 on day 14 of a cycle. Bleomycin, Adriamycin, cyclophosphamide, and vincristine are given on Day 1 of the cycle. Dexamethasone 6 mg/m2 is given orally on Days 1 through 5. The cycle is repeated on Day 21, and patients are treated with 10 such cycles for a total of 30 weeks. Of our 42 patients who are evaluable for response and who have completed chemotherapy, 33 (78%) achieved a complete remission (CR). A total of seven patients have relapsed. Only one patient in the CR group has relapsed in the CNS after the cessation of chemotherapy.