title: Neoadjuvant Sequential Docetaxel Followed by High-Dose Epirubicin in Combination With Cyclophosphamide Administered Concurrently With Trastuzumab. The DECT Trial.
abstract: To report the results of the DECT trial, a phase II study of locally advanced or operable HER2-positive breast cancer (BC) treated with taxanes and concurrent anthracyclines and trastuzumab. Eligible patients (stage IIA-IIIB HER2-positive BC, 18-75 years, normal organ functions, ECOG ≤1, and left ventricular ejection fraction (LVEF) ≥55%) received four cycles of neoadjuvant docetaxel, 100 mg/m(2) intravenously, plus trastuzumab 6 mg/kg (loading dose 8 mg/kg) every 3 weeks, followed by four 3-weekly cycles of epirubicin 120 mg/m(2) and cyclophosphamide, 600 mg/m(2) , plus trastuzumab. Primary objective was pathologic complete response (pCR) rate, defined as ypT0/is ypN0 at definitive surgery. We enrolled 45 consecutive patients. All but six patients (13.3%) completed chemotherapy and all underwent surgery. pCR was observed in 28 patients (62.2%) overall and in 6 (66.7%) from the inflammatory subgroup. The classification and regression tree analysis showed a 100% pCR rate in patients with BMI ≥25 and with hormone negative disease. The median follow up was 46 months (8-78). Four-year recurrence-free survival was 74.7% (95%CI, 58.2-91.2). Seven patients (15.6%) recurred and one died. Treatment was well tolerated, with limiting toxicity being neutropenia. No clinical cardiotoxicity was observed. Six patients (13.4%) showed a transient LVEF decrease (<10%). In one patient we observed a ≥10% asymptomatic LVEF decrease persisting after surgery. Notwithstanding their limited applicability due to the current guidelines, our findings support the efficacy of the regimen of interest in the neoadjuvant setting along with a fairly acceptable toxicity profile, including cardiotoxicity. Results on BMI may invite further assessment in future studies. J. Cell. Physiol. 231: 2541-2547, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.
authors.affiliation: Division of Medical Oncology 2, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Pizzuti
authors.affiliation: Division of Medical Oncology 2, Regina Elena National Cancer Institute, Rome, Italy.|Scientific Direction, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Barba
authors.affiliation: Biostatistics Unit, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Giannarelli
authors.affiliation: Division of Medical Oncology 2, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Sergi
authors.affiliation: Department of Surgery, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Botti
authors.affiliation: Oncology Unit, Sant'Andrea Hospital, La Sapienza University of Rome, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Marchetti
authors.affiliation: Department of Surgery, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Anzà
authors.affiliation: Division of Medical Oncology 2, Regina Elena National Cancer Institute, Rome, Italy.|Scientific Direction, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Maugeri-Saccà
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences and CeSI-MeT, G. d'Annunzio University, Chieti, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Natoli
authors.affiliation: Santa Maria Goretti, Hospital of Latina, Latina, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Di Filippo
authors.affiliation: Division of Medical Oncology 2, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Catenaro
authors.affiliation: Department of Gynecologic Oncology, University "Sapienza", Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Tomao
authors.affiliation: Division of Medical Oncology 2, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Amodio
authors.affiliation: Division of Medical Oncology 2, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Carpano
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Perracchio
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Mottolese
authors.affiliation: Division of Medical Oncology 2, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Di Lauro
authors.affiliation: Department of Radiation Oncology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sanguineti
authors.affiliation: Department of Pathology, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Di Benedetto
authors.affiliation: Sbarro Institute for Cancer Research and Molecular Medicine and Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania.
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.affiliation: Division of Medical Oncology 2, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Vici
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects; D009367:Neoplasm Staging; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*; D000068878:Trastuzumab / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D015251:Epirubicin; D003520:Cyclophosphamide; D000068878:Trastuzumab