title: Preoperative versus postoperative docetaxel-cisplatin-fluorouracil (TCF) chemotherapy in locally advanced resectable gastric carcinoma: 10-year follow-up of the SAKK 43/99 phase III trial.
abstract: BACKGROUND
  Fluorouracil-based adjuvant chemotherapy in gastric cancer has been reported to be effective by several meta-analyses. Perioperative chemotherapy in locally advanced resectable gastric cancer (RGC) has been reported improving survival by two large randomized trials and recent meta-analyses but the role of neoadjuvant chemotherapy and optimal regimen remains to be determined. We compared a neoadjuvant with adjuvant docetaxel-based regimen in a prospective randomized phase III trial, of which we present the 10-year follow-up data.
  
  
  METHODS
  Patients with cT3-4 anyN M0 or anyT cN1-3 M0 gastric carcinoma, staged with endoscopic ultrasound, computed tomography, bone scan, and laparoscopy, were assigned to receive four 21-day/cycles of docetaxel 75 mg/m(2) day 1, cisplatin 75 mg/m(2) day 1, and fluorouracil 300 mg/m(2)/day over days 1-14, either before (arm A) or after (arm B) gastrectomy. Event-free survival was the primary end point, whereas secondary end points included overall survival, toxicity, down-staging, pathological response, quality of life, and feasibility of adjuvant chemotherapy.
  
  
  RESULTS
  This trial was activated in November 1999 and closed in November 2005 due to insufficient accrual. Of the 70 enrolled patients, 69 were randomized, 34 to arm A and 35 to arm B. No difference in EFS (2.5 years in both arms) or OS (4.3 versus 3.7 years, in arms A and B, respectively) was found. A higher dose intensity of chemotherapy was observed in arm A and more frequent chemotherapy-related serious adverse events occurred in arm B. Surgery was safe after preoperative chemotherapy. A 12% pathological complete response was observed in arm A.
  
  
  CONCLUSIONS
  Docetaxel/cisplatin/fluorouracil chemotherapy is promising in preoperative setting of locally advanced RGC. The early stopping could mask the real effectiveness of neoadjuvant treatment. However, the complete pathological tumour responses, feasibility, and safe surgery warrant further investigation of a taxane-based regimen in the preoperative setting.
authors.affiliation: Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors nicola.fazio@ieo.it.
authors.forename: N
authors.initials: N
authors.lastname: Fazio
authors.affiliation: Division of Gastro-Intestinal Surgery, European Institute of Oncology (IEO), Milan, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Biffi
authors.affiliation: SAKK Coordinating Center, Bern.
authors.forename: R
authors.initials: R
authors.lastname: Maibach
authors.affiliation: SAKK Coordinating Center, Bern.
authors.forename: S
authors.initials: S
authors.lastname: Hayoz
authors.affiliation: SAKK Coordinating Center, Bern.
authors.forename: S
authors.initials: S
authors.lastname: Thierstein
authors.affiliation: SAKK Coordinating Center, Bern.
authors.forename: P
authors.initials: P
authors.lastname: Brauchli
authors.affiliation: IBCSG Coordinating Center, Bern Inselspital, Bern.
authors.forename: J
authors.initials: J
authors.lastname: Bernhard
authors.affiliation: Multidisciplinary Oncology Center, University Hospital (CHUV), Lausanne, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Stupp
authors.affiliation: Division of General Surgery and Laparoscopy, IEO, Milan and University of Milan, Milan.
authors.forename: B
authors.initials: B
authors.lastname: Andreoni
authors.affiliation: Department of Pathology and Laboratory Medicine.
authors.forename: G
authors.initials: G
authors.lastname: Renne
authors.affiliation: Division of Endoscopy, IEO, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Crosta
authors.affiliation: Kantonsspital, St Gallen.
authors.forename: R
authors.initials: R
authors.lastname: Morant
authors.affiliation: Division of Gastro-Intestinal Surgery, European Institute of Oncology (IEO), Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Chiappa
authors.affiliation: Division of Gastro-Intestinal Surgery, European Institute of Oncology (IEO), Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Luca
authors.affiliation: Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors.
authors.forename: M G
authors.initials: MG
authors.lastname: Zampino
authors.affiliation: Visceral Surgery, Department of Surgery, Geneva University Hospital, Geneva, Switzerland.
authors.forename: O
authors.initials: O
authors.lastname: Huber
authors.affiliation: Division of Medical Oncology, IEO, Milan.
authors.forename: A
authors.initials: A
authors.lastname: Goldhirsch
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: de Braud
authors.affiliation: Oncosurgery Unit, Department of Medicine, Geneva University Hospital, Geneva, Switzerland.
authors.forename: A D
authors.initials: AD
authors.lastname: Roth
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D000077143:Docetaxel; D005472:Fluorouracil / Q000008:administration & dosage; D005743:Gastrectomy; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D059035:Perioperative Period; D011184:Postoperative Period; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D002945:Cisplatin; D005472:Fluorouracil
keywords: TCF; chemotherapy; docetaxel; gastric cancer; neoadjuvant; preoperative