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Clinical Trial
. 2012 May 1;30(13):1476-83.
doi: 10.1200/JCO.2011.39.6853. Epub 2012 Mar 19.

Phase II study of bevacizumab in patients with HIV-associated Kaposi's sarcoma receiving antiretroviral therapy

Thomas S Uldrick  1 , Kathleen M Wyvill, Pallavi Kumar, Deirdre O'Mahony, Wendy Bernstein, Karen Aleman, Mark N Polizzotto, Seth M Steinberg, Stefania Pittaluga, Vickie Marshall, Denise Whitby, Richard F Little, Robert Yarchoan
Affiliations
Clinical Trial

Phase II study of bevacizumab in patients with HIV-associated Kaposi's sarcoma receiving antiretroviral therapy

Thomas S Uldrick et al. J Clin Oncol. .

Abstract

Purpose: Alternatives to cytotoxic agents are desirable for patients with HIV-associated Kaposi's sarcoma (KS). Vascular endothelial growth factor-A (VEGF-A) contributes to KS pathogenesis. We evaluated the humanized anti-VEGF-A monoclonal antibody, bevacizumab, in patients with HIV-KS.

Patients and methods: Patients with HIV-KS who either experienced progression while receiving highly active antiretroviral therapy (HAART) for at least 1 month or did not regress despite HAART for at least 4 months were administered bevacizumab 15 mg/kg intravenously on days 1 and 8 and then every 3 weeks. The primary objective was assessment of antitumor activity using modified AIDS Clinical Trial Group (ACTG) criteria for HIV-KS. HIV-uninfected patients were also eligible and observed separately.

Results: Seventeen HIV-infected patients were enrolled. Fourteen patients had been receiving effective HAART for at least 6 months (median, 1 year). Thirteen patients had advanced disease (ACTG T(1)), 13 patients had received prior chemotherapy for KS, and seven patients had CD4 count less than 200 cells/μL. Median number of cycles was 10 (range, 1 to 37 cycles); median follow-up was 8.3 months (range, 3 to 36 months). Of 16 assessable patients, best tumor responses observed were complete response (CR) in three patients (19%), partial response (PR) in two patients (12%), stable disease in nine patients (56%), and progressive disease in two patients (12%). Overall response rate (CR + PR) was 31% (95% CI, 11% to 58.7%). Four of five responders had received prior chemotherapy for KS. Over 202 cycles, grade 3 to 4 adverse events at least possibly attributed to therapy included hypertension (n = 7), neutropenia (n = 5), cellulitis (n = 3), and headache (n = 2).

Conclusion: Bevacizumab is tolerated in patients with HIV-KS and has activity in a subset of patients.

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Conflict of interest statement

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

Figures

Fig 1.
Fig 1.
Resolution of a Kaposi's sarcoma (KS) –associated chylous pleural effusion in a patient receiving bevacizumab. A 44-year-old man with HIV and KS had dramatic worsening of KS after starting highly active antiretroviral therapy, with development of greater than 50 cutaneous lesions, KS involving pelvic and inguinal lymph nodes, bilateral pleural effusions draining up to 6 L a week, and bilateral lower extremity edema. Analysis of the effusions did not reveal evidence of primary effusion lymphoma. The patient received 10 cycles of liposomal doxorubicin with some improvement in cutaneous lesions but no resolution of effusion, which required a right-sided indwelling pleural catheter. He also had continued lower extremity edema requiring daily diuretics. Within the first two cycles of bevacizumab, the effusions stopped draining, lower extremity swelling resolved, and diuretics were discontinued. (A) Posterior-anterior and (B) lateral chest x-rays at baseline. Bilateral pleural effusions and indwelling pleural catheter are on right. Pleural fluid was chylous (effusion triglycerides 1,905 mg/dL). (C) Posterior-anterior and (D) lateral chest x-rays at month 3 on bevacizumab. The effusions are resolved, and the indwelling catheter has been removed.
Fig 2.
Fig 2.
Kaplan-Meier progression-free survival (PFS) curve in 16 patients with HIV-associated Kaposi's sarcoma (KS) on highly active antiretroviral therapy treated with bevacizumab. Median follow-up until progression or censoring for these 16 patients was 5.4 months (range, 3 to 36 months). Median time to progression was 8.3 months. Hatch marks denote time patients are censored. One patient with limited KS who had transient initial progression followed by lasting complete response was considered progression free in PFS analysis.
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References

    1. Chang Y, Cesarman E, Pessin MS, et al. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science. 1994;266:1865–1869. - PubMed
    1. Whitby D, Howard MR, Tenant-Flowers M, et al. Detection of Kaposi sarcoma associated herpesvirus in peripheral blood of HIV-infected individuals and progression to Kaposi's sarcoma. Lancet. 1995;346:799–802. - PubMed
    1. Moore PS, Kingsley LA, Holmberg SD, et al. Kaposi's sarcoma-associated herpesvirus infection prior to onset of Kaposi's sarcoma. AIDS. 1996;10:175–180. - PubMed
    1. Engels EA, Biggar RJ, Hall HI, et al. Cancer risk in people infected with human immunodeficiency virus in the United States. Int J Cancer. 2008;123:187–194. - PubMed
    1. Shiels MS, Pfeiffer RM, Gail MH, et al. Cancer burden in the HIV-infected population in the United States. J Natl Cancer Inst. 2011;103:753–762. - PMC - PubMed

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