Abstract | PURPOSE: 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/m(2)/d. Prior KS therapy was reported by 17 patients (94%). COL-3-related 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). 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.
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Authors | Mary Cianfrocca, Timothy P Cooley, Jeannette Y Lee, Michelle A Rudek, David T Scadden, Lee Ratner, James M Pluda, William D Figg, Susan E Krown, Bruce J Dezube |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 20
Issue 1
Pg. 153-9
(Jan 01 2002)
ISSN: 0732-183X [Print] United States |
PMID | 11773164
(Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antineoplastic Agents
- Endothelial Growth Factors
- Lymphokines
- Matrix Metalloproteinase Inhibitors
- Tetracyclines
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factors
- tetracycline CMT-3
- Fibroblast Growth Factor 2
- Matrix Metalloproteinase 2
- Matrix Metalloproteinase 9
- Tetracycline
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Topics |
- Administration, Oral
- Adult
- Antineoplastic Agents
(adverse effects, pharmacology, therapeutic use)
- Endothelial Growth Factors
(blood)
- Female
- Fibroblast Growth Factor 2
(blood, drug effects)
- HIV Infections
(complications)
- Humans
- Lymphokines
(blood, drug effects)
- Male
- Matrix Metalloproteinase 2
(blood, drug effects)
- Matrix Metalloproteinase 9
(blood, drug effects)
- Matrix Metalloproteinase Inhibitors
- Middle Aged
- Sarcoma, Kaposi
(drug therapy, etiology)
- Statistics, Nonparametric
- Tetracycline
(adverse effects, pharmacology, therapeutic use)
- Tetracyclines
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factors
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