Originally published as JCO Early Release 10.1200/JCO.2008.18.7641 on May 26 2009

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Dose-Modified Oral Chemotherapy in the Treatment of AIDS-Related Non-Hodgkin's Lymphoma in East Africa

Walter O. Mwanda, Jackson Orem, Pingfu Fu, Cecilia Banura, Joweria Kakembo, Caren Auma Onyango, Anne Ness, Sherrie Reynolds, John L. Johnson, Vivek Subbiah, Jacob Bako, Henry Wabinga, Fatuma K. Abdallah, Howard J. Meyerson, Christopher C. Whalen, Michael M. Lederman, Jodi Black, Leona W. Ayers, Edward Katongole-Mbidde, Scot C. Remick

From the Department of Pathology, Section of Hematology and Blood Transfusion, Kenyatta National Hospital, University of Nairobi, College of Health Sciences, Nairobi, Kenya; Uganda Cancer Institute, Makerere University School of Medicine, Kampala; Uganda Virus Research Institute, Entebbe, Uganda; Center for AIDS Research, AIDS Malignancies Working Group; Case Comprehensive Cancer Center, Developmental Therapeutics Program and Clinical Trials Shared Resource; Departments of Biostatistics Epidemiology, Medicine, and Pathology; and Fogarty AIDS International Training and Research Program, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland; Department of Pathology, Ohio State University – AIDS and Cancer Specimen Resource, Columbus, OH; Mary Babb Randolph Cancer Center, West Virginia University School of Medicine, Morgantown, WV; and Translational Genomics Research Institute, Phoenix, AZ.

Corresponding author: Edward Katongole-Mbidde, MB, ChB, Uganda Virus Research Institute, P.O. Box 49, Entebbe, Uganda; e-mail: mbiddek{at}ug.cdc.gov.

Purpose Africa is burdened by the AIDS epidemic and attendant increase in HIV/AIDS-related malignancies. Pragmatic approaches to therapeutic intervention could be of great value. Dose-modified oral chemotherapy for AIDS-related non-Hodgkin's lymphoma is one such approach.

Patients and Methods The oral regimen consisted of lomustine 50 mg/m² on day 1 (cycle 1 only), etoposide 100 mg/m² on days 1 to 3, and cyclophosphamide/procarbazine 50 mg/m² each on days 22 to 26 at 6-week intervals (one cycle) for two total cycles in HIV-infected patients with biopsy-proven non-Hodgkin's lymphoma.

Results Forty-nine patients (21 in Uganda and 28 in Kenya) were treated. The majority of patients were female (59%) and had a poor performance status (63%); 69% of patients had advanced-stage disease; and 18 patients (37%) had access to antiretroviral therapy. In total, 79.5 cycles of therapy were administered. The regimen was well tolerated, had modest effects (decline) on CD4⁺ lymphocyte counts (P = .077), and had negligible effects on HIV-1 viral replication. Four febrile neutropenia episodes and three treatment-related deaths (6% mortality rate) occurred. The overall objective response rate was 78% (95% CI, 62% to 88%); median follow-up time was 8.2 months (range, 0.1 to 71 months); median event-free and overall survival times were 7.9 months (95% CI, 3.3 to 13.0 months) and 12.3 months (95% CI, 4.9 to 32.4 months), respectively; and 33% of patients survived 5 years.

Conclusion Dose-modified oral chemotherapy is efficacious, has comparable outcome to that in the United States in the pre–highly active antiretroviral therapy setting, has an acceptable safety profile, and is pragmatic in sub-Saharan Africa. The international collaboration has been highly successful, and subsequent projects should focus on strategies to optimize combination antiretroviral therapy and chemotherapy and follow-up tissue correlative studies.

W.O.M. and J.O. contributed equally to this work.

Supported in part by National Institutes of Health Grants No. CA83528, AI36219, CA70081, CA43703, CA066531, and TW00011. Bristol-Myers Squibb (Kenilworth, NJ) and Sigma Tau Pharmaceuticals (Rome, Italy) provided the chemotherapy drugs for this trial.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical Trials repository link available on JCO.org.

Clinical trial information can be found for the following: NCT00049439.

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