Use of trastuzumab associated with cisplatin and vinorelbine followed by docetaxel as a neoadjuvant regimen for patients with HER2-positive breast cancer.

Abstract

637 Background: Some clinical trials have shown the efficacy of neoadjuvant trastuzumab in HER2- positive breast cancer patients. Cardiotoxicity is a relatively frequent side effect, particularly when the drug is associated with anthracyclines or after radiotherapy on chest wall. A reduced heart function is a major issue in young patients and may restrict the use of trastuzumab as adjuvant treatment. Methods: Since 2007 to 2009 we enrolled HER2-positive breast cancer patients into a phase II study of primary systemic therapy. The trial was designed for testing anticancer agents with proven efficacy, synergy with trastuzumab, and mild cardiotoxicity. Weekly trastuzumab was administered in combination with 6 courses of sequential chemotherapy, including 3 cycles of cisplatin 80 mg/m2 on d1 plus vinorelbine 25 mg/m2 on d1+8 q3w, followed by 3 cycles of docetaxel 100 mg/m2 q3w. Peg-filgrastim was given to prevent neutropenia and to potentiate the proposed mechanisms of action of trastuzumab, such as activation of the immune system. Surgery was performed within 5 weeks after the treatment completion. Radiation and endocrine therapy were delivered according to standard practice guidelines. One year of postoperative trastuzumab was planned too. The primary objective was the rate of pathologic complete response (pCR). Secondary end-points included safety and rate of successful breast-conserving surgery. Results: Among 31 evaluable patients, 13 and 18 of them had stage II and III tumours, respectively. Five women (16%) received a diagnosis of stage IIIB breast cancer, including two cases of tumour spreading to skin (T4b) and three cases of inflammatory carcinoma (T4d). Median age was 47 years (range 23-70). Two patients had synchronous bilateral cancers. The rate of pCR was 38% (12/31). Among 29 patients initially proposable for demolitive operation, 17 of them (58%) finally received breast-conserving surgery. Treatment was well tolerated. No case of LVEF decrease or other severe toxicities was recorded. Alopecia was only moderate. Conclusions: Trastuzumab associated with cisplatin and vinorelbine followed by docetaxel was a feasible and safe neoadjuvant regimen. No significant financial relationships to disclose.