A Phase II Study of Imatinib Mesylate and Capecitabine in Metastatic Breast Cancer: Southwest Oncology Group Study 0338

Background: Imatinib mesylate is a potent inhibitor of the Bcr-Abl, c-Kit, and platelet-derived growth factor receptor (PDGFR) tyrosine kinases. On the basis of variable expression of c-Kit and PDGFR in breast cancer and of in vitro data supporting synergy between imatinib and capecitabine, the Southwest Oncology Group conducted a phase II trial of the combination in metastatic breast cancer. Patients and Methods: Eligible patients had progressive, measurable metastatic breast cancer and received :5 2 previous chemotherapy regimens for metastatic disease. Previous 5-fluorouracil or capecitabine for metastatic disease was not allowed. Patients were accrued on a 2-stage design and received imatinib mesylate 400 mg by mouth daily and capecitabine at 1000 mg/m(2) by mouth twice daily for 14 days of a 21-day cycle. The primary endpoint was the confirmed response rate (RR). Tumors were evaluated for c-Kit, PDGFR-P, and hormone receptor expression. Results: Nineteen fully evaluable patients were enrolled, with a confirmed RR of 11% (95% CI, 1%-33%). Eleven percent had unconfirmed partial responses, and 42% had stable disease. The trial did not accrue to the second stage. The estimated 6-month progression-free survival was 16% (95% CI, 0%-32%), and the median overall survival was 14 months (95% CI, 7-15 months). The combination was well tolerated. Of 8 available tumor samples, 2 stained for c-Kit, and all had stromal staining for PDGFR-P. Conclusion: In unselected patients, the combination of imatinib mesylate and capecitabine was well tolerated but did not result in improved RRs compared to those reported with capecitabine alone.