{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T23:09:37Z","timestamp":1791155377875,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2008,1,25]],"date-time":"2008-01-25T00:00:00Z","timestamp":1201219200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2008,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND.<\/jats:title><jats:p>Matrix metalloproteinases (MMPs) are overexpressed in Kaposi sarcoma (KS). The safety and efficacy of a novel, orally bioavailable MMP inhibitor, BMS\u2010275291, was evaluated in patients with human immunodeficiency virus\u2010associated KS and the correlation between changes in the percentage of apoptotic cells in tumor biopsies and response was explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS.<\/jats:title><jats:p>Cohorts of 6 patients were to be treated with BMS\u2010275291. The initial cohort received 1200 mg once a day; subsequent doses were to be escalated to 600 mg twice daily and 1200 mg twice daily, or decreased to 600 mg\/day. Tumor biopsies for apoptosis assays were collected pretreatment and on Day 29. Prospectively defined dose level adjustments were to be based on dose\u2010limiting toxicity (DLT), tolerability, changes in the percentage of apoptotic cells, and treatment response.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS.<\/jats:title><jats:p>Sixteen patients were enrolled; 15 received the study drug and could be evaluated. The median duration of treatment was 20 weeks (range, 3\u201354 weeks). A dose of 1200 mg once a day was well tolerated but induced only 1 response. A DLT occurred in 3 patients treated with 600 mg twice daily, and included grade 3 fatigue, grade 3 allergic reaction, and grade 3 arthralgias; 2 responses were noted at this dose level (toxicity was graded according to the National Cancer Institute Common Toxicity Criteria [version 2.0]). Based on predetermined endpoints, the trial was closed after accrual of 15 treated patients. Assessment of biologic response for dose escalation\/de\u2010escalation decisions utilizing the apoptosis assay was not feasible.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS.<\/jats:title><jats:p>BMS\u2010275291 given at a dose of 600 mg twice daily induced unacceptable toxicity. The better\u2010tolerated schedule of 1200 mg once a day demonstrated inadequate efficacy in patients with human immunodeficiency virus\u2010associated KS. The apoptosis assay was not helpful in predicting response. 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