title: Adjuvant treatment of high-risk, radically resected gastric cancer patients with 5-fluorouracil, leucovorin, cisplatin, and epidoxorubicin in a randomized controlled trial.
abstract: BACKGROUND
  Promising findings obtained using a weekly regimen of 5-fluorouracil (5-FU), epidoxorubicin, leucovorin (LV), and cisplatin (PELFw) to treat locally advanced and metastatic gastric cancer prompted the Italian Group for the Study of Digestive Tract Cancer (GISCAD) to investigate the efficacy of this regimen as adjuvant treatment for high-risk radically resected gastric cancer patients.
  
  
  METHODS
  From January 1998 to January 2003, 400 gastric cancer patients at high risk for recurrence including patients with serosal invasion (stage pT3 N0) and/or lymph node metastasis (stage pT2 or pT3 N1, N2, or N3), were enrolled in a trial of adjuvant chemotherapies; 201 patients were randomly assigned to receive the PELFw regimen, consisting of eight weekly administrations of cisplatin (40 mg/m2), LV (250 mg/m2), epidoxorubicin (35 mg/m2), 5-FU (500 mg/m2), and glutathione (1.5 g/m2) with the support of filgrastim, and 196 patients were assigned to a regimen consisting of six monthly administrations of a 5-day course of 5-FU (375 mg/m2 daily) and LV (20 mg/m2 daily, 5-FU/LV). Disease-free and overall survival were estimated and compared between arms using hazard ratios (HRs) and Kaplan-Meier estimates. All statistical tests were two-sided.
  
  
  RESULTS
  The 5-year survival rates were 52% in the PELFw arm and 50% in the 5-FU/LV arm. Compared with the 5-FU/LV regimen, the PELFw regimen did not reduce the risk of death (HR = 0.95, 95% confidence interval [CI] = 0.70 to 1.29) or relapse (HR = 0.98, 95% CI = 0.75 to 1.29). Less than 10% of patients in either arm experienced a grade 3 or 4 toxic episode. Neutropenia (occurring more often in the PELFw arm) and diarrhea and mucositis (more prevalent in the 5-FU/LV arm) were the most common serious side effects. Nevertheless, only 19 patients (9.4%) completed the treatment in the PELFw arm and 85 (43%) patients completed the treatment in the 5-FU/LV arm.
  
  
  CONCLUSIONS
  Our study found no benefit from an intensive weekly chemotherapy in gastric cancer. The extent of toxicity experienced by the patients in the adjuvant setting suggests that, in gastric cancer, chemotherapy may be more safely administered preoperatively.
authors: Universita' Politecnica delle Marche, Via Conca 60020 Ancona, Italy. cascinu@yahoo.com
authors: Stefano
authors: S
authors: Cascinu
authors: Roberto
authors: R
authors: Labianca
authors: Carlo
authors: C
authors: Barone
authors: Armando
authors: A
authors: Santoro
authors: Carlo
authors: C
authors: Carnaghi
authors: Alessandra
authors: A
authors: Cassano
authors: Giordano D
authors: GD
authors: Beretta
authors: Vincenzo
authors: V
authors: Catalano
authors: Oscar
authors: O
authors: Bertetto
authors: Sandro
authors: S
authors: Barni
authors: Luciano
authors: L
authors: Frontini
authors: Enrico
authors: E
authors: Aitini
authors: Silvia
authors: S
authors: Rota
authors: Valter
authors: V
authors: Torri
authors: Irene
authors: I
authors: Floriani
authors: Carmelo
authors: C
authors: Pozzo
authors: Lorenza
authors: L
authors: Rimassa
authors: Stefania
authors: S
authors: Mosconi
authors: Paolo
authors: P
authors: Giordani
authors: Antonio
authors: A
authors: Ardizzoia
authors: Paolo
authors: P
authors: Foa
authors: Carla
authors: C
authors: Rabbi
authors: Silvana
authors: S
authors: Chiara
authors: Giampietro
authors: G
authors: Gasparini
authors: Mario
authors: M
authors: Nardi
authors: Mauro
authors: M
authors: Mansutti
authors: Ermenegildo
authors: E
authors: Arnoldi
authors: Elena
authors: E
authors: Piazza
authors: Enrico
authors: E
authors: Cortesi
authors: Francesca
authors: F
authors: Pucci
authors: Rosa Rita
authors: RR
authors: Silva
authors: Alberto
authors: A
authors: Sobrero
authors: Alberto
authors: A
authors: Ravaioli
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis
chemical_list: D015251:Epirubicin; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil