{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T23:10:01Z","timestamp":1791155401093,"version":"4.1.0"},"reference-count":31,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2002,1,1]]},"abstract":"<jats:p>PURPOSE: Matrix metalloproteinases (MMPs) are involved in tumor invasion and metastasis and are overexpressed in Kaposi\u2019s 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).<\/jats:p><jats:p>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.<\/jats:p><jats:p>RESULTS: Eighteen patients received COL-3 in dosing cohorts of 25, 50, and 70 mg\/m<jats:sup>2<\/jats:sup>\/d. Prior KS therapy was reported by 17 patients (94%). COL-3\u2013related grade 3 or 4 adverse events were reported by six patients and included photosensitivity, rash, and headache. There was one complete response and seven partial responses, for an overall response rate of 44%, with a median response duration of 25+ weeks. The median COL-3 half-life was 39.3 hours (range, 4.1 to 251.1 hours). There was a significant difference between responders and nonresponders with respect to the change in MMP-2 serum levels from baseline to minimum value on treatment (P = .037).<\/jats:p><jats:p>CONCLUSION: COL-3 administered orally once daily to patients with AIDS-related KS is reasonably well tolerated. The most common adverse event was dose-related photosensitivity. Antitumor activity was noted. Further evaluation of COL-3 for the treatment of KS is warranted.<\/jats:p>","DOI":"10.1200\/jco.2002.20.1.153","type":"journal-article","created":{"date-parts":[[2017,2,24]],"date-time":"2017-02-24T00:38:26Z","timestamp":1487896706000},"page":"153-159","source":"Crossref","is-referenced-by-count":13,"title":["Matrix Metalloproteinase Inhibitor COL-3 in the Treatment of AIDS-Related Kaposi\u2019s Sarcoma: A Phase I AIDS Malignancy Consortium Study"],"prefix":"10.1200","volume":"20","author":[{"given":"Mary","family":"Cianfrocca","sequence":"first","affiliation":[{"name":"From the Beth Israel Deaconess Medical Center; Boston Medical Center; and Massachusetts General Hospital, Boston, MA; Northwestern University, Chicago, IL; Washington University, St Louis, MO; Memorial Sloan-Kettering Cancer Center, New York, NY; Clinical Pharmacokinetics Section and Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD; and AIDS Malignancy Consortium Operations Center, University of Alabama at Birmingham, Birmingham, AL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy P.","family":"Cooley","sequence":"additional","affiliation":[{"name":"From the Beth Israel Deaconess Medical Center; Boston Medical Center; and Massachusetts General Hospital, Boston, MA; Northwestern University, Chicago, IL; Washington University, St Louis, MO; Memorial Sloan-Kettering Cancer Center, New York, NY; Clinical Pharmacokinetics Section and Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD; and AIDS Malignancy Consortium Operations Center, University of Alabama at Birmingham, Birmingham, AL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeannette Y.","family":"Lee","sequence":"additional","affiliation":[{"name":"From the Beth Israel Deaconess Medical Center; Boston Medical Center; and Massachusetts General Hospital, Boston, MA; Northwestern University, Chicago, IL; Washington University, St Louis, MO; Memorial Sloan-Kettering Cancer Center, New York, NY; Clinical Pharmacokinetics Section and Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD; and AIDS Malignancy Consortium Operations Center, University of Alabama at Birmingham, Birmingham, AL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle A.","family":"Rudek","sequence":"additional","affiliation":[{"name":"From the Beth Israel Deaconess Medical Center; Boston Medical Center; and Massachusetts General Hospital, Boston, MA; Northwestern University, Chicago, IL; Washington University, St Louis, MO; Memorial Sloan-Kettering Cancer Center, New York, NY; Clinical Pharmacokinetics Section and Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD; and AIDS Malignancy Consortium Operations Center, University of Alabama at Birmingham, Birmingham, AL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T.","family":"Scadden","sequence":"additional","affiliation":[{"name":"From the Beth Israel Deaconess Medical Center; Boston Medical Center; and Massachusetts General Hospital, Boston, MA; Northwestern University, Chicago, IL; Washington University, St Louis, MO; Memorial Sloan-Kettering Cancer Center, New York, NY; Clinical Pharmacokinetics Section and Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD; and AIDS Malignancy Consortium Operations Center, University of Alabama at Birmingham, Birmingham, AL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee","family":"Ratner","sequence":"additional","affiliation":[{"name":"From the Beth Israel Deaconess Medical Center; Boston Medical Center; and Massachusetts General Hospital, Boston, MA; Northwestern University, Chicago, IL; Washington University, St Louis, MO; Memorial Sloan-Kettering Cancer Center, New York, NY; Clinical Pharmacokinetics Section and Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD; and AIDS Malignancy Consortium Operations Center, University of Alabama at Birmingham, Birmingham, AL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Pluda","sequence":"additional","affiliation":[{"name":"From the Beth Israel Deaconess Medical Center; Boston Medical Center; and Massachusetts General Hospital, Boston, MA; Northwestern University, Chicago, IL; Washington University, St Louis, MO; Memorial Sloan-Kettering Cancer Center, New York, NY; Clinical Pharmacokinetics Section and Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD; and AIDS Malignancy Consortium Operations Center, University of Alabama at Birmingham, Birmingham, AL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William D.","family":"Figg","sequence":"additional","affiliation":[{"name":"From the Beth Israel Deaconess Medical Center; Boston Medical Center; and Massachusetts General Hospital, Boston, MA; Northwestern University, Chicago, IL; Washington University, St Louis, MO; Memorial Sloan-Kettering Cancer Center, New York, NY; Clinical Pharmacokinetics Section and Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD; and AIDS Malignancy Consortium Operations Center, University of Alabama at Birmingham, Birmingham, AL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan E.","family":"Krown","sequence":"additional","affiliation":[{"name":"From the Beth Israel Deaconess Medical Center; Boston Medical Center; and Massachusetts General Hospital, Boston, MA; Northwestern University, Chicago, IL; Washington University, St Louis, MO; Memorial Sloan-Kettering Cancer Center, New York, NY; Clinical Pharmacokinetics Section and Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD; and AIDS Malignancy Consortium Operations Center, University of Alabama at Birmingham, Birmingham, AL."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce J.","family":"Dezube","sequence":"additional","affiliation":[{"name":"From the Beth Israel Deaconess Medical Center; 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