Matrix Metalloproteinase Inhibitor COL-3 in the Treatment of AIDS-Related Kaposi's Sarcoma: A Phase I AIDS Malignancy Consortium Study

Abstract

PURPOSE: Matrix metalloproteinases (MMPs) are involved in tumor invasion and metastasis and are overexpressed in Kaposi’s sarcoma (KS) cells. The primary aim was to define the safety and toxicity of the MMP inhibitor COL-3 in patients with AIDS-related KS. Secondary aims were to evaluate tumor response, pharmacokinetics, and changes in blood levels of MMP-2, MMP-9, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF). PATIENTS AND METHODS: COL-3 was administered orally once daily, and doses were escalated in cohorts of three to six subjects. Patients with symptomatic visceral KS or severe tumor-associated edema were excluded. Antiretroviral therapy was permitted but not required. Study end points were grade 3 or 4 toxicity or progressive KS. Serial blood specimens were obtained for pharmacokinetics and levels of MMP-2, MMP-9, VEGF, and bFGF. RESULTS: Eighteen patients received COL-3 in dosing cohorts of 25, 50, and 70 mg/m2/d. Prior KS therapy was reported by 17 patients (9...