Low-Dose Compared with Standard-Dose m-BACOD Chemotherapy for Non-Hodgkin's Lymphoma Associated with Human Immunodeficiency Virus Infection
Lawrence D. Kaplan, M.D., David J. Straus, M.D., Marcia A. Testa, M.P.H., Ph.D., Jamie Von Roenn, M.D., Bruce J. Dezube, M.D., Timothy P. Cooley, M.D., Brian Herndier, M.D., Ph.D., Donald W. Northfelt, M.D., Jenny Huang, M.S., Anil Tulpule, M.D., Alexandra M. Levine, M.D., for The National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group
Background Reduced doses of cytotoxic chemotherapy or standard-dosetherapy plus a myeloid colony-stimulating factor decreases hematologictoxicity and its complications in patients with non-Hodgkin'slymphoma associated with infection with the human immunodeficiencyvirus (HIV). However, the effect of reducing the doses of cytotoxicchemotherapeutic agents on clinical outcome is not known.
Methods We randomly assigned 198 HIV-seropositive patients withpreviously untreated, aggressive non-Hodgkin's lymphoma to receivestandard-dose therapy with methotrexate, bleomycin, doxorubicin,cyclophosphamide, vincristine, and dexamethasone (m-BACOD) alongwith granulocytemacrophage colony-stimulating factor(GM-CSF; n = 94) or reduced-dose m-BACOD with GM-CSF administeredonly as indicated (n = 98).
Results A complete response was achieved in 39 of the 94 assessablepatients assigned to low-dose therapy (41 percent) and in 42of the 81 assessable patients assigned to standard-dose therapy(52 percent, P = 0.56). There were no significant differencesin overall or disease-free survival; median survival times were35 weeks for patients receiving low-dose therapy and 31 weeksfor those receiving standard-dose therapy (risk ratio for deathin the standard-dose group, 1.17; 95 percent confidence interval,0.84 to 1.63; P =0.25). Toxic effects of chemotherapy ratedgrade 3 or higher occurred in 66 of 94 patients assigned tostandard-dose therapy (70 percent) and 50 of 98 patients assignedto low-dose treatment (51 percent, P = 0.008). Hematologic toxicityaccounted for the difference.
Conclusions As compared with treatment with standard doses ofcytotoxic chemotherapy (m-BACOD), reduced doses caused significantlyfewer hematologic toxic effects yet had similar efficacy inpatients with HIV-related lymphoma. Dose-modified chemotherapyshould be considered for most HIV-infected patients with lymphoma.
Source Information
From the Departments of Medicine (L.D.K.) and Pathology (B.H.), San Francisco General Hospital, and the Department of Medicine, University of California, San Francisco (L.D.K., D.W.N.) both in San Francisco; Memorial Sloan-Kettering Cancer Center and Cornell University Medical College, New York (D.J.S.); the Statistics and Data Analysis Center, Harvard School of Public Health, Boston (M.A.T., J.H.); the Department of HematologyOncology, Northwestern University, Chicago (J.V.R.); Beth Israel Deaconess Medical Center, Boston (B.J.D.); the Sections of Hematology and Oncology, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston (T.P.C.); and the University of Southern California Norris Cancer Hospital, University of Southern California School of Medicine, Los Angeles (A.T., A.M.L.).
Address reprint requests to Dr. Kaplan at the University of California, San Francisco San Francisco General Hospital AIDS Program, Oncology Division, Ward 84, 995 Potrero Ave., San Francisco, CA 94110.
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