title: Preoperative weekly cisplatin, epirubicin, and paclitaxel (PET) improves prognosis in locally advanced breast cancer patients: an update of the Southern Italy Cooperative Oncology Group (SICOG) randomised trial 9908.
abstract: BACKGROUND
  The present article reports the updated survival outcome of the 200 patients enrolled in the Southern Italy Cooperative Oncology Group 9908 trial, which compared 12 weekly cycles of cisplatin-epirubicin-paclitaxel (PET) with 4 triweekly (once every 3 weeks) cycles of epirubicin-paclitaxel (ET) in patients with locally advanced breast cancer (LABC).
  
  
  METHODS
  The effects of treatment, pathologically documented response (pathological response), pre- and post-treatment biomarkers on relapse-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS) are analysed.
  
  
  RESULTS
  At a median follow-up of 74 (range 48-105 months) months, the 5-year RFS, DMFS, and OS were 64 % versus 53% (P = 0.11), 73% versus 55% (P = 0.04), and 82% versus 69% (P = 0.07) in PET and ET, respectively. At multivariate analysis, after adjusting treatment effect for pretreatment biomarkers, PET independently predicted better DMFS (P = 0.018) and OS (P = 0.03), whereas the impact on RFS was of borderline significance (0.057). PET treatment was significantly better than ET treatment only in high-grade or highly proliferating tumours. The better outcome in PET arm was the results of both the higher rate of patients with optimal pathological response and the lower rate of patients with biologically aggressive residual tumour.
  
  
  CONCLUSIONS
  The PET weekly regimen significantly improves both DMFS and OS in LABC patients, compared with the triweekly ET combination. The therapeutic advantage is limited to patients with highly aggressive tumours.
authors.affiliation: Department of Senology. Electronic address: giuseppe.frasci@libero.it.
authors.forename: G
authors.initials: G
authors.lastname: Frasci
authors.affiliation: Department of Senology.
authors.forename: G
authors.initials: G
authors.lastname: D'Aiuto
authors.affiliation: Department of Medical Oncology.
authors.forename: P
authors.initials: P
authors.lastname: Comella
authors.affiliation: Department of Senology.
authors.forename: M
authors.initials: M
authors.lastname: D'Aiuto
authors.affiliation: Department of Pathology.
authors.forename: M
authors.initials: M
authors.lastname: Di Bonito
authors.affiliation: Department of Senology.
authors.forename: P
authors.initials: P
authors.lastname: Ruffolo
authors.affiliation: Department of Medical Oncology.
authors.forename: G
authors.initials: G
authors.lastname: Iodice
authors.affiliation: Department of Radiology.
authors.forename: A
authors.initials: A
authors.lastname: Petrillo
authors.affiliation: Department of Nuclear Medicine.
authors.forename: S
authors.initials: S
authors.lastname: Lastoria
authors.affiliation: Department of Senology.
authors.forename: P
authors.initials: P
authors.lastname: Oliviero
authors.affiliation: Department of Senology.
authors.forename: I
authors.initials: I
authors.lastname: Capasso
authors.affiliation: Department of Epidemiology, National Cancer Institute, Naples.
authors.forename: M
authors.initials: M
authors.lastname: Montella
authors.affiliation: Department of Surgery, Faculty of Medicine, University 'Magna Grecia' of Catanzaro, Catanzaro.
authors.forename: C
authors.initials: C
authors.lastname: Siani
authors.affiliation: Department of Surgical and Anaesthesiological Sciences, Faculty of Medicine, University Federico II, Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Santangelo
authors.affiliation: Department of Psychology, Centre for Cognitive Neuroimaging, University of Glasgow, Glasgow, UK.
authors.forename: L
authors.initials: L
authors.lastname: Vizioli
authors.affiliation: Department of Medical Oncology.
authors.forename: G
authors.initials: G
authors.lastname: Comella
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D002277:Carcinoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D018450:Disease Progression; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007558:Italy; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D011300:Preoperative Care; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D043823:Taxoids; D015251:Epirubicin; D005047:Etoposide; D017239:Paclitaxel; D002945:Cisplatin