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Published on: September 14, 2010
Randomized phase II trial of matrix metalloproteinase inhibitor COL-3 in AIDS-related Kaposi's sarcoma: an AIDS
Bruce J Dezube1, Susan E Krown, Jeannette Y Lee
1Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. bdezube@bidmc.harvard.edu
Purpose:
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.
Insights
Matrix metalloproteinase (MMP) inhibitor COL-3 showed significant activity in treating AIDS-related Kaposi's sarcoma (KS). The 50 mg/day dose demonstrated a 41% response rate, indicating its potential as a well-tolerated therapeutic agent.
Area of Science:
- Oncology
- Virology
- Pharmacology
Background:
- Matrix metalloproteinases (MMPs) play a role in tumor metastasis and are overexpressed in Kaposi's sarcoma (KS).
- Previous phase I trials indicated MMP inhibitor COL-3 was well-tolerated and showed KS regression in patients with AIDS-related KS.
- MMP-2 levels decreased significantly in responders compared to nonresponders in initial studies.
Purpose of the Study:
- To evaluate the efficacy and tolerability of COL-3 in patients with AIDS-related KS.
- To extend initial observations from a phase I trial regarding COL-3's impact on KS and MMP levels.
Main Methods:
- A randomized, parallel-group, phase II study was conducted.
- Patients with AIDS-related KS received COL-3 orally at 50 mg (group A) or 100 mg (group B) daily.
- Serial tumor assessments and plasma MMP levels were monitored; study endpoints included progressive KS and dose-limiting toxicity.
Main Results:
- Seventy-five patients received COL-3; 57 had prior KS therapy and 33 had over 50 KS lesions.
- Group A (50 mg/day) achieved a 41% response rate, significantly exceeding the 20% target (P = .003).
- Significant declines in plasma MMP-2 and MMP-9 levels were observed with treatment (P < .001 and P = .001, respectively).
Conclusions:
- COL-3, at a dose of 50 mg/day, is active and well-tolerated for treating AIDS-related KS.
- COL-3 demonstrates promise as a therapeutic agent for this opportunistic neoplasm associated with AIDS.
- The drug's ability to reduce MMP levels further supports its potential mechanism of action in KS treatment.
