PILOT TRIAL OF INFUSIONAL CYCLOPHOSPHAMIDE, DOXORUBICIN, AND ETOPOSIDE PLUS DIDANOSINE AND FILGRASTIM IN PATIENTS WITH HUMAN IMMUNODEFICIENCY VIRUS-ASSOCIATED NON-HODGKINS-LYMPHOMA

Purpose: To determine the following: (1) the feasibility of combining the antiretroviral didanosine (ddl) with a 96-hour continuous intraven ous (IV) infusion of cyclophosphamide (800 mg/m(2)), doxorubicin (50 m g/m(2)), and etoposide (240 mg/m(2)) (CDE) plus filgrastim in patients with non-Hodgkin's lymphoma (NHL) associated with human immunodeficie ncy virus (HIV) infection; (2) the effect of ddl on CDE-induced myelos uppression and CD4 lymphopenia; and (3) the effect of CDE on serum p24 antigen and quantitative HIV blood cultures. Methods: Twenty-five pat ients with HIV-related NHL received CDE every 28 or more days, Consecu tive patients were assigned in an alternating fashion to group A (ddl given at a standard dose during cycles one, two, five, and six) or gro up B (ddl given during cycles three, four, five, and six). Results: dd l use was associated with less leukopenia (mean nadir, 3.33v1.49x10(3) /mu L; P=.03), neutropenia(2.38v1.07x10(3)/mu L; P=.03), and thrombocy topenia (76v48x10(3)/mu L; P=.059), and fewer RBC (1.6v3.1 per cycle; P <.01) and platelet transfusions (0.7v1.5 per cycle; P <.01), but had no significant effect on CD4 lymphopenia. Furthermore, lymphomatous b one marrow involvement and low CD4 count were associated with signific antly greater myelosuppression. Although there was no substantial chan ge in serum p24 antigen, the HIV blood culture became quantitatively m ore positive or converted from negative to positive in seven patients (64%). Complete response (CR) occurred in 58% of patients (95% confide nce interval, 38% to 78%), median CR duration exceeded 18 months, tumo r-related mortality was 20%, and median survival was 18.4 months. Conc lusion: Our results suggest that the CDE and filgrastim regimen is tol erable and effective for patients with HIV-associated NHL, and that co mbination with ddl is feasible and may result in less myelosuppression . (C) 1996 by American Society of Clinical Oncology.