title: Is it possible to increase pCR in the neoadjuvant treatment with a dose-dense/sequential combination?: results from a phase II Trial combining epirubicin and cyclophosphamide followed by paclitaxel and gemcitabine ± trastuzumab in stage II and III breast cancer patients.
abstract: OBJECTIVE
  To evaluate the pathologic complete response (pCR) rate of a combination of epirubicin (E) and cyclophosphamide (C) followed by paclitaxel (P) and gemcitabine (G) (+ trastuzumab[T]) in Her2+ patients) in a sequential and dose-dense schedule as neoadjuvant chemotherapy for stages II and III patients with breast cancer. Secondary endpoints: clinical response rate, disease free survival, safety and correlation between pCR and biologic markers.
  
  
  METHODS
  Eligible patients were treated with E (90 mg/m²) and C (600 mg/m²) for 3 cycles (first sequence) followed by P (150 mg/m²) and G (2500 mg/m²) (second sequence) for 6 cycles. All drugs were administered on day 1, every 2 weeks, with prophylactic growth factor support. Weekly T (2 mg/kg [4 mg/kg first infusion]) was administered concomitantly with P and G in Her2+ patients. A core biopsy was performed before treatment for biologic markers assessment. Patients underwent surgery, radiotherapy, and adjuvant hormonal therapy according to institutional practice.
  
  
  RESULTS
  Seventy-three patients were treated. A pCR was achieved in 27 (37%) patients (32.1%, Her2- and 50%, Her2+). pCR was significantly higher in tumors that were hormonal receptor negative, poorly differentiated and positive for Ki67 and p53. Breast-conserving surgery was performed in 47 patients (64.4%). Most frequent grade 3/4 hematologic and nonhematological toxicities included neutropenia (12%), nausea/vomiting (17%), and transient liver enzymes elevation (7%). One patient suffered an asymptomatic and reversible decrease in left ventricular ejection fraction.
  
  
  CONCLUSIONS
  These results show a highly effective regimen in terms of pCR with a good toxicity profile in the neoadjuvant treatment of patients with breast cancer. The addition of trastuzumab increased pCR rate in Her2+ tumors.
authors: Department of Oncology, Complejo Hospitalario de Jaén, Spain. asmoncomed@yahoo.es
authors: Alfonso
authors: A
authors: Sánchez-Muñoz
authors: R
authors: R
authors: Dueñas-García
authors: A
authors: A
authors: Jaén-Morago
authors: E
authors: E
authors: Carrasco
authors: I
authors: I
authors: Chacón
authors: A M
authors: AM
authors: García-Tapiador
authors: A L
authors: AL
authors: Ortega-Granados
authors: E
authors: E
authors: Martínez-Ortega
authors: N
authors: N
authors: Ribelles
authors: M
authors: M
authors: Fernández-Navarro
authors: C
authors: C
authors: de la Torre-Cabrera
authors: B
authors: B
authors: Dueñas
authors: A I
authors: AI
authors: Rueda
authors: J
authors: J
authors: Martínez
authors: C Ramírez
authors: CR
authors: Tortosa
authors: M D
authors: MD
authors: Martín-Salvago
authors: P
authors: P
authors: Sánchez-Rovira
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016019:Survival Analysis; D000068878:Trastuzumab; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003520:Cyclophosphamide; D003841:Deoxycytidine; D015251:Epirubicin; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D000093542:Gemcitabine; C508053:ERBB2 protein, human