Neoadjuvant Dose-Dense Gemcitabine plus Docetaxel and Vinorelbine plus Epirubicin for Operable Breast Cancer: Improved Prognosis in Triple-Negative Tumors

• Published in: Drugs in R&D 2011, Vol.11 (2), p.147-157
• Main Authors: Medioni, Jacques, Huchon, Cyrille, Le Frere-Belda, Marie-Aude, Hofmann, Henri, Bats, Anne-Sophie, Eme, Denise, Andrieu, Jean-Marie, Oudard, Stéphane, Lecuru, Fabrice, Levy, Eric
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Breast cancer; Breast Neoplasms - diagnosis; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Breast Neoplasms - radiotherapy; Breast Neoplasms - surgery; Cancer; Chemotherapy; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Drug therapy; Epirubicin - administration & dosage; Epirubicin - therapeutic use; Female; Health aspects; Humans; Internal Medicine; Lymphatic Metastasis - diagnosis; Medicine; Medicine & Public Health; Middle Aged; Neoadjuvant Therapy - methods; Neoplasm Grading; Neoplasm Metastasis - diagnosis; Neoplasm Recurrence, Local; Neoplasm Staging; Original; Original Research Article; Pharmacology/Toxicology; Pharmacotherapy; Prognosis; Receptor, ErbB-2 - genetics; Receptors, Estrogen - genetics; Receptors, Progesterone - genetics; Survival Analysis; Taxoids - administration & dosage; Taxoids - therapeutic use; Treatment Outcome; Vinblastine - administration & dosage; Vinblastine - analogs & derivatives; Vinblastine - therapeutic use; Young Adult
• ISSN: 1174-5886; 1179-6901
• DOI: 10.2165/11591210-000000000-00000

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/m 2 plus docetaxel 75 mg/m 2 on days 1 and 15, and vinorelbine 25 mg/m 2 plus epirubicin 100mg/m 2 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.