Phase II AIDS Malignancy Consortium trial of topical halofuginone in AIDS-related Kaposi sarcoma

Abstract

Using a novel blinded intrapatient vehicle control design, we conducted a phase II study of topically administered halofuginone, an angiogenesis inhibitor that inhibits collagen type-I and matrix metalloproteinases (MMPs), in patients with AIDS-related Kaposi sarcoma. Serial Kaposi sarcoma biopsies assessed treatment effects on angiogenic factors and Kaposi sarcoma herpesvirus-latency associated nuclear antigen-1 (KSHV-LANA). We observed marked heterogeneity of KSHV-LANA expression. Although the small number of subjects whose response could be evaluated precluded definitive assessment of halofuginone's efficacy, we observed a significant decrease in type-I collagen only in halofuginone-treated lesions, but no effect on MMP-2. The trial design is applicable to future studies of topical agents.

Figure 1. Immunohistochemical staining for KSHV LANA shows significant heterogeneity among different patients

A and B: a representative biopsy with a scant number of LANA-positive spindle cells. C and D: a biopsy from another patient with a moderate amount of LANA positivity. E and F: numerous LANA positive cells in a biopsy that showed a nodule with a dense concentration of spindle cells. (A,C,E: LANA, 2 × magnification; B,D,F: LANA, 20 × magnification).