Adjuvant treatment of high-risk, radically resected gastric cancer patients with 5-fluorouracil, leucovorin, cisplatin, and epidoxorubicin in a randomized controlled trial.
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.
Cascinu
Stefano
S
Universita' Politecnica delle Marche, Via Conca 60020 Ancona, Italy. cascinu@yahoo.com
Labianca
Roberto
R
Barone
Carlo
C
Santoro
Armando
A
Carnaghi
Carlo
C
Cassano
Alessandra
A
Beretta
Giordano D
GD
Catalano
Vincenzo
V
Bertetto
Oscar
O
Barni
Sandro
S
Frontini
Luciano
L
Aitini
Enrico
E
Rota
Silvia
S
Torri
Valter
V
Floriani
Irene
I
Pozzo
Carmelo
C
Rimassa
Lorenza
L
Mosconi
Stefania
S
Giordani
Paolo
P
Ardizzoia
Antonio
A
Foa
Paolo
P
Rabbi
Carla
C
Chiara
Silvana
S
Gasparini
Giampietro
G
Nardi
Mario
M
Mansutti
Mauro
M
Arnoldi
Ermenegildo
E
Piazza
Elena
E
Cortesi
Enrico
E
Pucci
Francesca
F
Silva
Rosa Rita
RR
Sobrero
Alberto
A
Ravaioli
Alberto
A
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
D015251:Epirubicin; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil