A Phase I Study of Capecitabine Combined with CPT-11 in Metastatic Breast Cancer Pretreated with Anthracyclines and Taxanes

Objective: A dose escalation study of biweekly irinotecan (CPT-11) combined with capecitabine was performed to determine the maximum tolerated dose (MTD) and recommended dose (RD) for metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes. Methods: Escalating doses of CPT-11 (80-120 mg/m2) were administered on days 1 and 15. Capecitabine was administered at a fixed dose of 1,657 mg/m2/day for 21 consecutive days, followed by 7 days of rest. We treated 3-6 patients at a particular dose level until the MTD was determined. Results: Twenty patients were treated. The MTD was determined to be 100 mg/m2, as 3 of 6 patients developed dose-limiting toxicities, grade 3 leukopenia, neutropenia, photophobia, fatigue and diarrhea. The RD for the phase II study was thus determined to be 90 mg/m2. The response rate was 41.7%. Conclusions: Combination therapy with CPT-11 and capecitabine was well tolerated with a promising response rate for MBC that had been treated previously with anthracyclines and taxanes. A multi-center phase II study is warranted to evaluate the efficacy and safety of this combination therapy with pharmacokinetic assessment.