Neoadjuvant vinorelbine/epirubicin (VE) versus standard adriamycin/ cyclophosphamide (AC) in operable breast cancer: Analysis of response and tolerability in a randomised phase III trial (TOPIC 2)

Background: Vinorelbine is active and well tolerated against advanced breast cancer but there are no published efficacy studies in early breast cancer. We have therefore carried out a randomised phase III neoadjuvant trial in operable breast cancer. Patients and methods: Pati ents with ≥3 cm operable breast carcinoma were randomised to receive either vinorelbine 25 mg/m² on days 1 and 8 and epirubicin 60 mg/m² on day 1, 3 weekly for six cycles (VE) or doxorubicin 60 mg/m² and cyclophosphamide 600 mg/m² i.v. on day 1, 3 weekly for six cycles (AC), prior to standard local therapy, and adjuvant endocrine therapy as appropriate. Results: A total of 451 patients were randomised. Results f or AC and VE, respectively, were: overall clinical response 73% and 74%, complete clinical remission 20% and 24%, pathological complete remission 12% and 12%, mastectomy rate 52% and 55%. None of these differences were significant. Dose reduction was required in 8% for AC and 20% for VE (P <0.001) (GSCF support not used). Significantly more grade 3/4 toxicity for nausea, vomiting and alopecia (despite scalp cooling) was seen for AC compared with VE but significantly less grade 3/4 thrombophlebitis and neuropathy. Conclusions: Neoadjuvant VE is as effective as AC in early breast cancer and was better tolerated except for thrombophlebitis and neuropathy.