Chemotherapy for human immunodeficiency virus-associated non-Hodgkin's lymphoma in combination with highly active antiretroviral therapy

Purpose: This study investigated the efficacy, toxicity, and pharmacokineti c interactions resulting from simultaneous combination chemotherapy and hig hly active antiretroviral therapy (HAART) for patients with human immunodef iciency virus (HIV)-associated non-Hodgkin's lymphoma (NHL). In addition, t he effects on viral load, CD4 counts, and opportunistic infections were exa mined with the use of combination chemotherapy combined with HAART. Patients and Methods: Sixty-five patients with previously untreated and mea surable disease at any stage of HIV-associated NHL of intermediate or high grade were entered onto this study at 17 different centers. The first 40 pa tients entered onto the study received reduced doses of cyclophosphamide an d doxorubicin, combined with vincristine and prednisone (modified CHOP [mCH OP]), whereas the subsequent 25 patients entered onto the study received fu ll doses of CHOP combined with granulocyte colony-stimulating factor (G-CSF ). All patients also received stavudine, lamivudine, and indinavir. Results: The complete response rates were 30% and 48% among patients who re ceived mCHOP and full-dose CHOP combined with HAART, respectively. Grade 3 or 4 neutropenia occurred in 25% of patients receiving mCHOP and 12% of tho se receiving full-dose CHOP combined with G-CSF (25% v 12%). There were sim ilar numbers of patients with grade 3 or 4 hyperbilirubinemia (12% and 17%) , constipation and abdominal pain (18% and 17%), and transaminase elevation (48% and 52%) on the modified and full-dose arms of the study, respectivel y. Doxorubicin clearance and indinavir concentration curves were similar am ong patients on this study and historical controls, whereas cyclophosphamid e clearance was 1.5-fold reduced as compared with control values. Human imm unodeficiency virus (HIV) load declined from a median baseline value of 29, 000 copies/mL to a median minimum value on therapy of 500 copies/mL. Conclusion: Either modified-dose or full-dose CHOP chemotherapy for HIV-NHL , delivered with HAART, is effective and tolerable. (C) 2001 by American So ciety of Clinical Oncology.