Phase II study of neoadjuvant docetaxel/vinorelbine followed by surgery and adjuvant doxorubicin/cyclophosphamide in women with stage II/III breast cancer

Background: The purpose of this study was to evaluate the combination of docetaxel plus vinorelbine as neoadjuvant chemotherapy for stage II/III locally advanced breast cancer. Patients and Methods: Eligible women wi th stage IIA-IIIB or locoregional stage IV breast cancer were treated before surgery with 6 cycles of docetaxel 60 mg/m² and vinorelbine 45 mg/m², repeated every 2 weeks with granulocyte colony-stimulating factor and quinolone prophylaxis. Pathologic complete response (pCR), viewed as an early surrogate for disease-free and overall survival, was the primary efficacy endpoint. Sixty patients were enrolled; 60% had T3 or T4 lesions, 67% had clinically palpable lymph nodes, and 52% were hormone receptor positive. Results: Fifty-nine patients were evaluable for path ologic response; 16 (27%) exhibited pCR in the breast alone (T0 Tis NX), 20% exhibited a pCR in the breast and lymph nodes (T0 Tis N0), 24 (41%) had < 5 mm of residual tumor, and 28 (47%) had node-negative disease at surgery. Relative dose intensity was 96% for docetaxel and 95% for vinorelbine. The clinical response rate was 98% (59 of 60 patients), including 38 complete responses (63%). Grade 3/4 neutropenia (95%), neutropenic fever (22%), mucositis (5%), and pulmonary toxicity (5%) occurred in ≥ 5% of patients. Constipation was seen early but became insignificant after incorporating a prophylactic laxative regimen. Other toxicities have been minimal. Conclusion: With a clinical response rate of 98% and an i n-breast pCR rate of 27%, docetaxel/vinorelbine is among the most active neoadjuvant regimens reported for locally advanced breast cancer. Docetaxel/ vinorelbine can be administered in a dose-dense fashion while maintaining relative dose intensity. However, there was a significant incidence of fever and neutropenia despite the use of prophylactic growth factors and quinolones, indicating that lower doses of docetaxel/ vinorelbine should be evaluated in future studies.