Capecitabine and paclitaxel combination chemotherapy for inoperable or recurrent breast cancer: a phase I dose-finding study by the Kinki Breast Cancer Study Group.

Background: The combination of capecitabine and paclitaxel (XP) has demonstrated synergistic antitumor activity in preclinical models. Three-weekly XP regimens have demonstrated excellent efficacy in phase II and III trials in metastatic breast cancer. We conducted a dose-finding study to identify the recommended 4-weekly XP regimen in patients with inoperable or recurrent breast cancer for phase II evaluation.

Methods: Eligible patients had inoperable or recurrent breast cancer previously treated with chemotherapy (but not capecitabine or paclitaxel) in the (neo)adjuvant or metastatic setting. Each 4-week treatment cycle consisted of escalating doses of capecitabine (628 or 829 mg/m(2) twice daily [b.i.d.] on days 1-21) and paclitaxel (80 or 90 mg/m(2) on days 1, 8, and 15). Dose-limiting toxicities (DLT) were evaluated during the first two cycles.

Results: Nine patients were treated. At dose level 1 (capecitabine 628 mg/m(2) b.i.d. plus paclitaxel 80 mg/m(2)), one patient experienced a DLT (grade 3 non-hematologic toxicity). There were no further DLTs at dose level 1 or 2. Although the MTD was not reached, dose level 2 (capecitabine 829 mg/m(2) b.i.d., days 1-21, plus paclitaxel 80 mg/m(2), days 1, 8, and 15, every 28 days) is recommended for phase II evaluation, taking into consideration the single-agent doses used in Japan and the doses identified in Western studies of 3-weekly XP. The overall response rate was 44%; all patients treated at dose level 2 achieved a partial response.

Conclusions: This 4-weekly XP regimen was well tolerated, active in patients with pretreated advanced breast cancer, and could be given as outpatient treatment. These results are consistent with findings of phase II and III trials evaluating 3-weekly regimens, and indicate that further investigation of a 4-weekly XP regimen is warranted.