title: Dose-modified oral chemotherapy in the treatment of AIDS-related non-Hodgkin's lymphoma in East Africa.
abstract: 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/m(2) on day 1 (cycle 1 only), etoposide 100 mg/m(2) on days 1 to 3, and cyclophosphamide/procarbazine 50 mg/m(2) 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.
authors.affiliation: Uganda Virus Research Institute, P.O. Box 49, Entebbe, Uganda.
authors.forename: Walter O
authors.initials: WO
authors.lastname: Mwanda
authors.forename: Jackson
authors.initials: J
authors.lastname: Orem
authors.forename: Pingfu
authors.initials: P
authors.lastname: Fu
authors.forename: Cecilia
authors.initials: C
authors.lastname: Banura
authors.forename: Joweria
authors.initials: J
authors.lastname: Kakembo
authors.forename: Caren Auma
authors.initials: CA
authors.lastname: Onyango
authors.forename: Anne
authors.initials: A
authors.lastname: Ness
authors.forename: Sherrie
authors.initials: S
authors.lastname: Reynolds
authors.forename: John L
authors.initials: JL
authors.lastname: Johnson
authors.forename: Vivek
authors.initials: V
authors.lastname: Subbiah
authors.forename: Jacob
authors.initials: J
authors.lastname: Bako
authors.forename: Henry
authors.initials: H
authors.lastname: Wabinga
authors.forename: Fatuma K
authors.initials: FK
authors.lastname: Abdallah
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Meyerson
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Whalen
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.forename: Jodi
authors.initials: J
authors.lastname: Black
authors.forename: Leona W
authors.initials: LW
authors.lastname: Ayers
authors.forename: Edward
authors.initials: E
authors.lastname: Katongole-Mbidde
authors.forename: Scot C
authors.initials: SC
authors.lastname: Remick
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D017954:Africa South of the Sahara; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000639:trends; D018791:CD4 Lymphocyte Count; D003520:Cyclophosphamide / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007630:Kenya; D008130:Lomustine / Q000627:therapeutic use; D016483:Lymphoma, AIDS-Related / Q000188:drug therapy*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality / Q000821:virology; D008297:Male; D008875:Middle Aged; D011344:Procarbazine / Q000627:therapeutic use; D016896:Treatment Outcome; D014454:Uganda; D014779:Virus Replication / Q000187:drug effects; D055815:Young Adult
chemical_list: D011344:Procarbazine; D005047:Etoposide; D008130:Lomustine; D003520:Cyclophosphamide