Vinorelbine plus trastuzumab combination as first-line therapy for HER 2-positive metastatic breast cancer patients: an international phase II trial

Abstract

The aim of this international phase II trial was to determine the efficacy and safety profile of weekly vinorelbine plus trastuzumab as first-line chemotherapy for women with HER 2-overexpressing metastatic breast cancer. Sixty-nine patients with tumours overexpressing HER 2 received vinorelbine: 30 mg m À2 week À1 and trastuzumab: 4 mg kg À1 on day 1 as a loading dose followed by 2 mg kg À1 week À1 starting on day 8. Sixty-two patients were evaluable for response and 69 patients were evaluable for toxicity. The overall response rate was 62.9%. The median time to response was 8.4 weeks, the median duration of response was 17.5 months, the median progression-free survival was 9.9 months (95% CI, 5.6 -12.1) and the one-year progression-free survival was 39.1%. The median survival for all patients was 23.7 months (95% CI, 18.4 -32.6). This regimen was safe: grade 3 -4 neutropenia were observed over 17.7% of courses in 83.8% of patients, with only two episodes of febrile neutropenia (0.1%) in two patients (2.9%). Only one patient discontinued treatment due to grade 3 symptomatic cardiac dysfunction that resolved with therapy. Vinorelbine plus trastuzumab is one of the most active treatment regimens for patients with HER 2-positive metastatic breast cancer and demonstrates a very favourable safety profile allowing prolonged treatment with long-term survival. This study has been presented in

The Trastuzumab and Vinorelbine Combination: An Alternative to Taxane-Based Chemotherapy for Early-Stage and Locally Advanced HER2-Positive Breast Cancer

“…Vinorelbine, a vinca alkaloid drug, was shown to have good synergistic activity with trastuzumab in preclinical studies 7 . Multiple phase ii trials of the trastuzumab-vinorelbine (tv) regimen in the metastatic setting have reported response rates of up to 86%, with manageable toxicity [8][9][10][11] . Two large phase iii randomized trials also reported similar efficacy and favourable toxicity for the tv regimen compared with taxane-based therapy in the metastatic setting 12,13 .…”

NK-cell and T-cell functions in patients with breast cancer: effects of surgery and adjuvant chemo- and radiotherapy

“…surgery, radiation treatment and/or chemotherapy) and ultimately relapse and die (Cheng et al, 2004). Her-2 targeting monoclonal antibodies such as trastuzumab, given as adjuvant therapy, have significantly improved the relapse-free survival of breast cancer patients (Chan et al, 2006). However, it is not yet clear whether adjuvant trastuzumab treatment ought to be incorporated early, that is together with chemotherapy, or late, that is after end of adjuvant chemo-radiotherapy (Gennari et al, 2004).…”

Treatment of Metastatic Breast Cancer

“…Here again, this choice is based on previously published data although only nonrandomized studies have shown the high efficacy of such a combination. 11,12 In addition, although our study does not provide data on tolerance, the lack of such secondary effects as alopecia may have influenced this choice. Furthermore, the overall cost for patients in group 1 was higher than that in group 2 and this difference is mainly because of the treatment cost.…”

“…No recommendation was made about previous treatment, and trastuzumab could be combined to either docetaxel or vinorelbine (Navelbine, Pierre Fabre Laboratories), based on the results of published studies showing high response rates [11][12][13] (50% to 70%) together with favorable survival results: 9.9 months for the median progression-free survival, 23.7 months for median survival. 12…”