Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/31396
Title: As-Needed Vs Immediate Etoposide Chemotherapy in Combination With Antiretroviral Therapy for Mild-to-Moderate AIDS-Associated Kaposi Sarcoma in Resource-Limited Settings: A5264/AMC-067 Randomized Clinical Trial
Authors: Hosseinipour, Mina C.
Kang, Minhee
Krown, Susan E.
Bukuru, Aggrey
Umbleja, Triin
Martin, Jeffrey N.
Orem, Jackson
Godfrey, Catherine
Hoagland, Brenda
Mwelase, Noluthando
Langat, Deborah
Nyirenda, Mulinda
MacRae, John
Borok, Margaret
Samaneka, Wadzanai
Moses, Agnes
Mngqbisa, Rosie
Busakhala, Naftali
Martínez-Maza, Otoniel
Ambinder, Richard
Dittmer, Dirk P.
Nokta, Mostafa
Campbell, Thomas B.
A5264/AMC-067 REACT-KS Team
Affilliation: UNC Project. Lilongwe, Malawi / University of North Carolina. School of Medicine. Chapel Hill, USA.
Harvard T.H. Chan School of Public Health. Center for Biostatistics in AIDS Research. Boston, Massachusetts, USA.
AIDS Malignancy Consortium. New York, USA.
Joint Clinical Research Center. Kampala, Uganda.
Harvard T.H. Chan School of Public Health. Center for Biostatistics in AIDS Research. Boston, Massachusetts, USA.
University of California. San Francisco, USA.
Uganda Cancer Institute. Kampala, Uganda.
National Institutes of Health. HIV Research Branch, Rockville, Maryland, USA.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.
University of Witwatersrand. Johannesburg, South Africa.
Kenya Medical Research Institute/Walter Reed Project. Kericho. Kenya.
Johns Hopkins Project. University of Malawi. College of Medicine. Blantyre, Malawi.
IMPACTA Peru. Lima, Peru.
AIDS Malignancy Consortium. New York, USA / University of Zimbabwe. Harare, Zimbabwe.
UNC Project. Lilongwe, Malawi / University of North Carolina. School of Medicine. Chapel Hill, USA./ AIDS Malignancy Consortium. New York, USA.
DICRS. Enhancing Care Foundation. Durban, South Africa.
Moi University. Eldoret, Kenya.
AIDS Malignancy Consortium. New York, USA / University of California. Los Angeles, USA.
AIDS Malignancy Consortium. New York, USA / Johns Hopkins University. Baltimore, USA.
University of North Carolina. School of Medicine. Chapel Hill, USA./ AIDS Malignancy Consortium. New York, USA.
National Cancer Institute. Bethesda, Maryland, USA.
University of Colorado. School of Medicine. Aurora, USA.
Abstract: Background. Mild-to-moderate AIDS-associated Kaposi sarcoma (KS) often responds to antiretroviral therapy (ART) alone; the role of chemotherapy is unclear. We assessed the impact of immediate vs as-needed oral etoposide (ET) among human immunodeficiency virus (HIV)–infected individuals with mild-to-moderate KS initiating ART. Methods. Chemotherapy-naive, HIV type 1–infected adults with mild-to-moderate KS initiating ART in Africa and South America were randomized to ART (tenofovir/emtricitabine/efavirenz) alone (chemotherapy “as-needed” arm) vs ART plus up to 8 cycles of oral ET (immediate arm). Participants with KS progression on ART alone received ET as part of the as-needed strategy. Primary outcome was ordinal as follows: failure, stable, and response at 48 weeks. Secondary outcomes included time to initial KS progression, KS-associated immune reconstitution inflammatory syndrome (KS-IRIS), and KS response. Results. Of 190 randomized participants (as-needed = 94, immediate = 96), the majority were men (71%) and African (93%). Failure (53.8% vs 56.6%), stable (16.3% vs 10.8%), and response (30% vs 32.5%) did not differ between arms (as-needed vs immediate) among those with week 48 data potential (N = 163, P = .91). Time to KS progression (P = .021), KS-IRIS (P = .003), and KS response (P = .003) favored the immediate arm. Twenty-five participants died (13%). Mortality, adverse events, CD4+ T-cell changes, and HIV RNA suppression were similar at 48 weeks. Conclusions. Among HIV-infected adults with mild-to-moderate KS, immediate ET provided early, nondurable clinical benefits. By 48 weeks, no clinical benefit was observed compared to use of ET as needed. Mortality was high and tumor response was low. Clinical Trials Registration. NCT01352117.
Keywords: Kaposi sarcoma
HIV
Etoposide
Chemotherapy
Antiretroviral therapy
Issue Date: 2018
Publisher: Oxford University Press
Citation: HOSSEINIPOUR, M. C. et al. As-Needed Vs Immediate Etoposide Chemotherapy in Combination With Antiretroviral Therapy for Mild-to-Moderate AIDS-Associated Kaposi Sarcoma in Resource-Limited Settings: A5264/AMC-067 Randomized Clinical Trial. Clinical Infectious Diseases, v. 67, n. 2, p. 251–260, 2018.
DOI: 10.1093/cid/ciy044
ISSN: 1058-4838
Copyright: restricted access
Appears in Collections:INI - Artigos de Periódicos

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