An oral-based combination chemotherapy regimen, consisting of lomustine (CCNU), etoposide (VP-16) cyclophosphamide and procarbazine, has been specifically developed for patients with AIDS-related non-Hodgkin's lymphoma (NHL). The overall objective response rate and median survival duration in 38 patients with advanced AIDS-NHL and poor prognostic factors enrolled on two studies of the regimen are comparable to previously reported intravenous chemotherapy regimens. Based on the results of the largest chemotherapy trial reported in 1997 by the ACTG in AIDS-related NHL, we plan to dose-modify the oral regimen in anticipation of improving the therapeutic index. A unique aspect of this proposal is to address the safety and utility of this regimen in adult men and women in East Africa, a region with a high burden of HIV infection and HIV-related malignancies. The attributes of the oral regimen in this setting are highly desirable and of paramount importance in medically underserved portions of the world. This proposal would support the first clinical trial in AIDS-related NHL in Uganda and Kenya with important laboratory correlative studies on: 1) underlying HIV infection including monitoring of CD4 lymphocyte counts and viral load; 2) underlying HHV-8 viral load in seropositive patients; and 3) procuring clinical samples and tumor specimens from all patients, and submitting them to the NCI-sponsored AIDS and Cancer Specimen Bank (ACSB) at the Ohio State University in Columbus, Ohio. The core is in place for the successful conduct of this proposal: Dr. Scot Remick, the PI of the project, is an expert in AIDS- related malignancies and Director of the CFAR International Clinical Coordination Center; our recent inclusion in the NCI- sponsored AIDS Malignancy Consortium (AMC), for which we plan to procure clinical and tumor samples for the ACSB and explore potential international collaborative activities with the AMC; the support of the CWRU Fogarty AIDS International Training and Research Program (AITRP); and fully functioning clinical and laboratory facilities in Uganda and Kenya. The goals are to establish response rates and toxicity profiles; to assess feasibility of treatment delivery and its impact on a large scale in the East African setting; to compare the course of (treated) AIDS-related lymphomas in Uganda and Kenya; to analyze the pathobiologic findings as prognostic factors for course of disease and/or treatment response and to analyze East African and US populations. The CWRU international programs and the CWRU - Columbia - New Jersey AIDS-Associated Malignancies Clinical Trials Unit (CCNJ-AAMCTU) are poised to serve as the springboard for potential future AMC international collaborative activities.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA083528-03
Application #
6661973
Study Section
AIDS and Related Research 8 (AARR)
Program Officer
Bhatia, Kishor
Project Start
2001-09-24
Project End
2007-08-31
Budget Start
2003-09-01
Budget End
2007-08-31
Support Year
3
Fiscal Year
2003
Total Cost
$305,190
Indirect Cost
Name
Case Western Reserve University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
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Mwanda, Walter O; Orem, Jackson; Fu, Pingfu et al. (2009) Dose-modified oral chemotherapy in the treatment of AIDS-related non-Hodgkin's lymphoma in East Africa. J Clin Oncol 27:3480-8
Orem, Jackson; Otieno, Mwanda W; Remick, Scot C (2006) Challenges and opportunities for treatment and research of AIDS-related malignancies in Africa. Curr Opin Oncol 18:479-86
Orem, Jackson; Otieno, Mwanda W; Remick, Scot C (2004) AIDS-associated cancer in developing nations. Curr Opin Oncol 16:468-76
Otieno, Mwanda W; Banura, Cecily; Katongole-Mbidde, Edward et al. (2002) Therapeutic challenges of AIDS-related non-Hodgkin's lymphoma in the United States and East Africa. J Natl Cancer Inst 94:718-32