Neoadjuvant Dose-Dense Gemcitabine plus Docetaxel and Vinorelbine plus Epirubicin for Operable Breast Cancer

Abstract

Background: Neoadjuvant anti-tumor activity of an alternating taxane- and anthracycline-based dose-dense regimen in patients with operable, noninflammatory large breast cancer was investigated.Objective: The objective is to study the rate of pathological complete response in patients with breast cancer receiving dose-dense chemotherapy sequentially with gemcitabine plus docetaxel and vinorelbine plus epirubicin.Methods: Women (n = 74) with clinical stage II or III breast cancer were enrolled in this open-label, multicenter study to receive six 2-weekly courses of gemcitabine 1000 mg/m2 plus docetaxel 75 mg/m2 on days 1 and 15, and vinorelbine 25 mg/m2 plus epirubicin 100mg/m2 on days 29 and 43. Patients with an objective response on day 56 then received another cycle of gemcitabine/ docetaxel on day 57 and of vinorelbine/epirubicin on day 71. Conservative surgery was scheduled for all patients.Results: Of the patients enrolled, 30% had triple-negative breast cancer (TNBC). The pathologic complete response (pCR) rate was 22% overall, but was higher in TNBC than patients without TNBC (40.9% vs 14.0%; p=0.028). Among patients with a pCR, patients with TNBC had similar recurrence-free survival (RFS) and overall survival (OS) to patients without TNBC. Among those without a pCR, RFS rates for patients with TNBC were significantly lower than for patients without TNBC (p=0.04). The most common severe hematologic toxicity was neutropenia.Conclusions: Administering four drugs in a dose-dense alternating sequence gave a high pCR in patients with operable, invasive breast cancer. Patients with TNBC with a pCR had similar OS to patients without TNBC, whereas patients with TNBC without a pCR had poorer survival rate than their non- TNBC counterparts.

Meta-analysis on the association between pathologic complete response and triple-negative breast cancer after neoadjuvant chemotherapy

“…Some researchers have demonstrated that the addition of platinum agents to anthracycline and/or taxane regimens in NAC has promise for outcomes [ 58 ]. Although the gemcitabine-containing group included two studies with 108 cases [ 15 , 31 ], we should not ignore this group, which achieved the highest pCR rate. Due to lack of sufficient cases to support gemcitabine use in NAC for TNBC, more clinical trials should be implemented.…”

Triple-Negative Breast Cancer: Expression of Hypoxia-Inducible Factor 1α in Triple-Negative Breast Cancer with Metastasis to Lymph Nodes

“…The current highest pCR rates, about 40-45%, are achieved by taxane/anthracycline sequential chemotherapy regimens and inclusion of platinum drugs with the taxane component. Inclusion or substitution of other chemotherapy drugs (capecitabine, gemcitabine, vinorelbine, or ixabepilone) resulted in little or no improvement in pCR rates [26,27]. To date, all clinical trials showed that the neoadjuvant chemotherapy was the preferred option for patients with TNBC who required systemic therapy.…”

Identified the novel resistant biomarkers for taxane-based therapy for triple-negative breast cancer

“…The most effective regimens for TNBC currently reach only 40-45% pathologic complete response (pCR) rates, which are achieved by taxane/anthracycline sequential treatment or combination of taxane with the platinum drugs 17 . Previous reports showed little or no improvement in pCR rates of other chemotherapy drugs such as capecitabine, gemcitabine, ixabepilone, or vinorelbine 17 - 19 . There is no valid biomarker or effective treatment target to predict taxane resistance in TNBC 9 , 20 .…”