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Clin Infect Dis. 2018 Jul 2;67(2):251-260. doi: 10.1093/cid/ciy044.

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.

Author information

1
UNC Project, Lilongwe, Malawi.
2
University of North Carolina School of Medicine, Chapel Hill.
3
Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
4
AIDS Malignancy Consortium, New York, New York.
5
Joint Clinical Research Center, Kampala, Uganda.
6
University of California, San Francisco.
7
Uganda Cancer Institute, Kampala.
8
HIV Research Branch, TRP, DAIDS, NIAID, National Institutes of Health, Rockville, Maryland.
9
INI Evandro Chagas/FIOCRUZ, Rio de Janiero, Brazil.
10
University of Witwatersrand, Johannesburg, South Africa.
11
Kenya Medical Research Institute/Walter Reed Project, Kericho.
12
Johns Hopkins Project, University of Malawi College of Medicine, Blantyre, Malawi.
13
IMPACTA Peru, Lima.
14
University of Zimbabwe, Harare.
15
DICRS, Enhancing Care Foundation, Durban, South Africa.
16
Moi University, Eldoret, Kenya.
17
University of California, Los Angeles.
18
Johns Hopkins University, Baltimore.
19
National Cancer Institute, Bethesda, Maryland.
20
University of Colorado School of Medicine, Aurora.

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.

PMID:
29365083
PMCID:
PMC6030807
DOI:
10.1093/cid/ciy044
[Indexed for MEDLINE]
Free PMC Article

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