3'-Azido 3'-deoxythymidine + methotrexate as a novel antineoplastic
combination in the treatment of human immunodeficiency virus-related
non-Hodgkin's lymphomas
P Tosi, F Gherlinzoni, P Mazza, G Visani, O Coronado, P Costigliola, E Raise, M Mazzetti, F Gritti, F Chiodo and S Tura
Istituto di Ematologia 'L. e A. Seragnoli', Policlinico S. Orsola, Bologna,
Italy.
We have previously reported that 3'-azido 3'-deoxythymidine (AZT) can
possess a significant antineoplastic activity when combined with drugs that
disrupt de novo thymidylate synthesis, such as 5-fluorouracil and
methotrexate (MTX). The aim of the present study was to evaluate the
efficacy and the tolerance of the combination AZT + MTX in human
immunodeficiency virus (HIV)-related non-Hodgkin's lymphoma (NHL).
Twenty-nine patients (22 men and 7 women), either newly diagnosed or
pretreated, have been enrolled in the trial; the median age was 34 years,
45% had acquired immunodeficiency syndrome before lymphoma and 19 patients
had less than 100 CD4 lymphocytes/microL. Histologic diagnoses were mainly
Burkitt (27%) and diffuse large B-cell lymphoma (45%); extranodal
involvement was present in 20 patients. The treatment plan included three
weekly courses of MTX at 1 g/m2 (days 1, 8, and 15) plus oral AZT at 2 g/m2
(days 1, 2, and 3), 4 g/m2 (days 8, 9, and 10), and 6 g/m2 (days 15, 16,
and 17), plus leucovorin rescue. From the eleventh patient on, in case of
complete or partial remission, the treatment was continued with three
additional courses, using AZT at the maximum dose. In 26 evaluable
patients, the total (complete + partial) response rate was 77% (95%
confidence interval, 58% to 89%), with complete remission (CR) in 46% of
the patients (95% confidence interval, 29% to 65%). The median CR duration
was 12.8 months. Grade III-IV neutropenia and anemia were observed in 52%
and 31% of the courses, respectively. There was one therapy-related death
due to bacteremia followed by septic shock; the only other recorded
infection was a herpes vaginalis. In conclusion, we suggest that AZT + MTX
is an effective and well-tolerated regimen in HIV-related NHL.
Volume 89,
Issue 2,
pp. 419-425,
01/15/1997
Copyright © 1997 by The American Society of Hematology
