Abstract
The efficacy of combination therapy including an oral gelatinase inhibitor (CT1746) and cytotoxic agent was analyzed using the murine Lewis lung carcinoma model. Primary tumors, pulmonary metastases, and sera from tumor-bearing animals had increased gelatinase B activity that was inhibited by CT1746 levels achievable in vivo. The combination of CT1746 and cyclophosphamide (CTX) was significantly more effective than either single agent in delaying local tumor growth (CT1746/CTX, 30.9 ± 1.7 days; CT1746, 2.6 ± 0.3 days; CTX, 19.5 ± 1.1 days; P < .001) and reducing the number and size of pulmonary metastases [CT1746/CTX, 5 ± 2 (15% metastases > 3 mm); CT1746, 15 ± 4 (55% > 3 mm); CTX, 11 ± 3 (63% > 3 mm); no treatment, 24 ± 5 (62% > 3 mm); P < .001]. These data support the notion of combining matrix metalloproteinase inhibitors and cytotoxic agents to treat certain epithelial malignancies.
Footnotes
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↵1 To whom requests for reprints should be addressed, at Division of Hematologic Malignancies, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115.
- Received December 12, 1995.
- Accepted January 2, 1996.
- ©1996 American Association for Cancer Research.
Volume 56, Issue 4
