5-year results of cisplatin-epirubicin-vinorelbine (PEV) combination as primary chemotherapy in T2-3, N0-2 breast cancer patients: a multicentre phase II study.

The aim this study was to assess the efficacy of cisplatin-epirubicin-vinorelbine, as primary chemotherapy, in reducing the tumour burden in T2-3 N0-2 breast carcinomas. Breast conservative surgery (BCS) rate, clinical and pathological complete response (pCR), toxicity and 5-year disease-free survival (DFS) and overall survival (OS) were evaluated. Patients and Methods: Eighty-eight women with tumours ≥2.5 cm were treated with cisplatin (P) 50 mg/m 2 , epirubicin (E) 100 mg/m 2 and vinorelbine (V) 25 mg/m 2 , every 3 weeks. Results: Fifty-six out of the 88 patients (63.6%) underwent BCS, notably including 12/23 patients with initial tumours >5 cm. The overall clinical response was 72.8% (cCR=11.4%), pCR 20.5% and pT0+pN0 17%. No cardiac toxicity was observed. Grade 3/4 adverse events were leukopenia (9.4%), neutropenia (7.9%), nausea and vomiting (7.3%). After a median follow-up of 5 years, 24 patients (27.3%) had developed local or distant metastases. The mean DFS and OS were 51.7 (SE 2.38) and 57.02 (SE 1.98) months, respectively, and were significantly higher in pCR patients in comparison to the others (63.05 vs. 48.76, p<0.01 and 64.59 vs. 55.04, p<0.05, respectively). Conclusion: The PEV regimen was highly effective in reducing the tumour burden, especially for large tumours. The rate of pCR was similar to that obtained by other, including taxane-based regimens, and was well-tolerated. The study demonstrated the feasibility of such a regimen even in small centres, and being of low cost this combination could be of value in the application of primary therapy. Studies which have been conducted since the early 1980s in breast cancer patients with stage I-IIIb disease, have demonstrated clinical tumour regression in 70-75%, whereas a complete clinical response was observed in about 26% (1). These initial reports have shown a significant activity of primary chemotherapy, an increase in the number of women offered breast conservation treatment and no apparent detrimental effect on survival. More recent studies (2, 3) have shown a pathological complete response (pCR) rate of 16-19% and demonstrated that 5-year disease-free survival (DFS) (89% vs. 64%) and overall survival (OS) (87% vs. 58%) were higher in those patients with a pCR compared to those with any other response to primary chemotherapy. Although different synergistic regimens have been studied in order to evaluate if combination chemotherapy with non-cross resistant drugs could improve the response rate and the breast conservative rate, most studies concerning preoperative therapy have consisted of anthracycline-based regimens. Our previous experience, with a multicentre phase II study using the combination cisplatin (P)-epirubicin (E)-