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Randomized phase II trial of matrix metalloproteinase inhibitor COL-3 in AIDS-related Kaposi's sarcoma: an AIDS Malignancy Consortium Study.

AbstractPURPOSE:
Matrix metalloproteinases (MMPs) are involved in tumor metastasis and are overexpressed in Kaposi's sarcoma (KS) cells. In a phase I trial of the MMP inhibitor COL-3 in patients with AIDS-related KS, the drug was well tolerated, KS regression was observed, and MMP-2 levels decreased significantly in responders compared with nonresponders. The aim of this trial was to extend these initial observations.
PATIENTS AND METHODS:
This was a randomized, parallel-group, phase II study. COL-3 was administered orally once daily at one of two doses (group A received 50 mg and group B received 100 mg) to patients with AIDS-related KS. Antiretroviral therapy was permitted but not required. Serial tumor assessments and plasma levels of MMPs were obtained. Study end points were progressive KS and recurrent dose-limiting toxicity.
RESULTS:
Seventy-five patients received COL-3: 37 in group A and 38 in group B. Fifty-seven patients (76%) had received prior KS therapy. Thirty-three patients (44%) had more than 50 KS lesions. The response rate in group A was 41%, which was significantly greater than the prespecified target rate of 20% (95% CI, 25% to 58%; P = .003); the response rate of group B was 29% (P = not significant). There were significant declines in MMP-2 and MMP-9 plasma levels from baseline to minimum value with treatment (MMP-2, P < .001; MMP-9, P = .001). The most common adverse events were photosensitivity and rash.
CONCLUSION:
COL-3, when administered as 50 mg/d, is both active and well tolerated in the treatment of AIDS-related KS. COL-3 is a promising agent for the treatment of this opportunistic neoplasm of AIDS.
AuthorsBruce J Dezube, Susan E Krown, Jeannette Y Lee, Kenneth S Bauer, David M Aboulafia
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 24 Issue 9 Pg. 1389-94 (Mar 20 2006) ISSN: 1527-7755 [Electronic] United States
PMID16549833 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Tetracyclines
  • tetracycline CMT-3
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
Topics
  • Acquired Immunodeficiency Syndrome (complications)
  • Administration, Oral
  • Adult
  • Aged
  • Disease Progression
  • Female
  • Humans
  • Male
  • Matrix Metalloproteinase 2 (blood)
  • Matrix Metalloproteinase 9 (blood)
  • Middle Aged
  • Sarcoma, Kaposi (drug therapy)
  • Tetracyclines (administration & dosage, therapeutic use)
  • Treatment Outcome

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