Phase II Study of Bevacizumab in Patients With HIV-Associated Kaposi's Sarcoma Receiving Antiretroviral Therapy

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 T1), 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.

Pomalidomide for Symptomatic Kaposi's Sarcoma in People With and Without HIV Infection: A Phase I/II Study

“…Thalidomide and related drugs are known to modulate VEGF pathways, which are upregulated by KSHV and crucial to the pathogenesis of KS, 29 and have effects on several cytokines implicated in KS pathogenesis, including interleukin-6. 30 The response rate observed here is substantially higher than that reported with VEGF-specific therapies in KS, 19 suggesting that VEGF alone is not the primary target of pomalidomide in KS, but that it or other cytokine pathways could be additional contributors to activity.…”

“…19 To be evaluable for response, completion of two cycles of therapy was required. Evaluations included lesion counts, measurement of the sum product of the diameters of five indicator lesions, assessment of number of nodular lesions, and measurement of limb circumference if tumor-associated edema was present.…”

Multivariate discriminant analysis of redox and progression indexes in Cuban AIDS patients with Kaposis sarcoma

“…Substantial progress has been made toward an integrative understanding to delineate mechanisms considering oxidative stress and ROS as potential key participants in cancer development [59]. In this sense, significant difference evidenced in some redox indexes related to progression markers and also to clinical condition evaluated by discriminant analysis support association to HIV infection evolution.…”

Kaposi’s Sarcoma Epidemiology, Risk Factors, Staging and Treatment: AN OVERVIEW.

“…In a phase II study with HIV associated KS, imatinib induced partial response in one third of patients [78]. In another phase II study, the monoclonal anti-VEGF antibody, bevacizumab had an overall response rate of 31 % [79]. Angiogenesis inhibitors may have a role in combination therapy, and the combination of bevacizumab with liposomal doxorubicin is being evaluated (NCT00923936).…”