AZT+methotrexate in high-grade HIV-related non-Hodgkin lymphomas: interim report on feasibility and tolerance

Istituto di Ematologia, L. e A. Seragnoli, University of Bologna, Italy.

BACKGROUND. 3' azido-3' deoxythymidine (AZT) is a thymidine analogue useful in the treatment of AIDS. We have previously demonstrated that AZT can possess significant antineoplastic activity when combined with de novo thymidylate synthesis inhibitors, such as 5-fluorouracil or methotrexate (MTX). We report here on the feasibility and tolerance of the combination AZT+MTX in the treatment of HIV-related non-Hodgkin lymphomas (NHL). PATIENTS AND METHODS. IV-positive patients with high-grade NHL were treated, at weekly intervals, with three consecutive courses of MTX 1 g/m2 plus increasing doses of oral AZT (2, 4 and 6 g/m2) and folinic acid rescue. RESULTS. From July 1992 to June 1994, 16 patients were enrolled in the trial after giving informed consent. Grade III-IV neutropenia was observed after 22% of the courses, but was prevented by G-CSF administration in 34/59 courses. Grade III-IV anemia was observed after 15% of the courses. No non hematological toxicity was observed. CONCLUSIONS. The combination AZT+MTX was extremely well tolerated in this series of HIV-related NHL patients. If these results are confirmed in terms of antineoplastic efficacy, the protocol will deserve wider application.