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Background Rationale The survival improvement observed with capecitabine/docetaxel in patients with metastatic disease has led to the hypothesis that this regimen could improve the outcome of patients with early-stage breast cancer. Several trials 3-5 have shown that the sequential administration of preoperative docetaxel following an anthracycline-based regimen improves outcome and pathologic complete response rates in both the lymph nodes and breast. It is hoped that adding capecitabine to docetaxel will further improve the outcome of patients receiving adjuvant chemotherapy. - Back to top Eligibility For enrollment in US Oncology trial 01062, patients are required to have breast cancer staged T1-3 N1 M0 or T2 N0 M0. Patients with T1c N0 M0 are eligible if their tumors are estrogen receptor (ER)/progesterone receptor (PR) negative. Patients are also required to be aged < 70 years. The ER/PR status of the tumor must be known. Patients must also have good kidney and liver function. Patients with a positive (lesion > 2 mm) sentinel lymph node biopsy must undergo axillary lymph node dissection. Patients with evidence of metastatic disease are ineligible. - Back to top Treatment On US Oncology 01062, eligible patients are randomized to postoperative treatment with standard doxorubicin/cyclophosphamide (AC) (60 mg/m2 and 600 mg/m2) for 4 cycles followed by either docetaxel 100 mg/m2 every 3 weeks x 4 cycles or docetaxel 75 mg/m2 plus capecitabine given on days 1-14, every 3 weeks x 4 cycles (Figure 1). The dose of capecitabine was initially 950 mg/m2 p.o. b.i.d. in this trial based on the toxicity data from the phase III trial in MBC, which showed that a 25% reduction in the initial dose of capecitabine (from 1250 mg/m2 p.o. b.i.d.) led to a 50% reduction in the incidence of severe toxicities. Analysis of TTP and OS data from the phase III MBC trial showed that a 25% reduction in the capecitabine dose did not lessen the efficacy of the capecitabine/docetaxel combination. The 01062 protocol was recently amended because > 50% of the patients required a capecitabine dose reduction at some point during cycles 5-8 in the first 60 patients who completed 4 cycles of chemotherapy. The starting dose of capecitabine has been reduced from 1900 mg/m2/day (950 mg/m2 b.i.d.) to 1650 mg/m2/day (825 mg/m2 b.i.d.) (Table 2). Clinical research coordinators (CRCs) and physicians should emphasize to the patients that they are to stop capecitabine and call the CRC for any grade 2 toxicity. If patients develop capecitabine-related toxicity, every effort should be made to keep patients on capecitabine with appropriate dose reduction so as not to decrease the curative potential of their adjuvant chemotherapy. - Back to top Statistics The primary hypothesis of this trial is that a 25% improvement in disease-free survival with AC—› capecitabine/docetaxel will be observed compared with AC—› docetaxel alone. This study has a 90% power to detect a significant difference between the 2 study arms. Two interim safety analyses will be conducted when 150 and 500 patients have completed all 8 cycles of chemotherapy. An interim efficacy analysis will be conducted at 3 years median follow-up. Target accrual is 2400 patients (Table 3). - Back to top References
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