Adjuvant chemotherapy in completely resected gastric cancer: a randomized phase III trial conducted by GOIRC.
BACKGROUND
Complete surgical resection of gastric cancer is potentially curative, but long-term survival is poor.


METHODS
Patients with histologically proven adenocarcinoma of the stomach of stages IB, II, IIIA and B, or IV (T4N2M0) and treated with potentially curative surgery were randomly assigned to follow-up alone or to intravenous treatment with four cycles (repeated every 21 days) of PELF (cisplatin [40 mg/m(2), on days 1 and 5], epirubicin [30 mg/m(2), days 1 and 5], L-leucovorin [100 mg/m(2), days 1-4], and 5-fluorouracil [300 mg/m(2), days 1-4] in a hospital setting. Frequencies and severity of adverse events were determined. Overall survival (OS) and disease-free survival (DFS) were compared between the treatment arms using Kaplan-Meier analysis and a Cox proportional hazards regression model. All statistical tests were two-sided.


RESULTS
From January 1995 through September 2000, 258 patients were randomly assigned to chemotherapy (n = 130) or surgery alone (n = 128). Patient characteristics were well balanced between the two arms. Among those who received chemotherapy, grade 3 or 4 toxic effects including vomiting, mucositis, and diarrhea were experienced by 21.1%, 8.4%, and 11.8% of patients, respectively. Leucopenia, anemia, and thrombocytopenia of grade 3 or 4 were experienced by 20.3%, 3.3%, and 4.2% of patients, respectively. After a median follow-up of 72.8 months, 128 patients (49.6%) experienced recurrence and 139 (53.9%) deaths were observed, one toxicity-related. Relative to treatment with surgery alone, adjuvant chemotherapy did not increase disease-free survival (hazard ratio [HR] of recurrence = 0.92; 95% confidence interval [CI] = 0.66 to 1.27) or overall survival (HR of death = 0.90; 95% CI = 0.64 to 1.26).


CONCLUSIONS
Our results failed to provide proof of an effect of adjuvant chemotherapy with PELF on overall survival or disease-free survival. The estimated effect of chemotherapy (10% reduction in the hazard of death or relapse) is modest and consistent with the results of meta-analyses of adjuvant chemotherapy without platinum agents.
Di Costanzo
Francesco
F
Unit of Medical Oncology, Azienda Ospedaliero Universitaria Careggi, Viale Pieraccini 17, 50139 Florence, Italy. dicostanzofrancesco@tiscali.it
Gasperoni
Silvia
S
Manzione
Luigi
L
Bisagni
Giancarlo
G
Labianca
Roberto
R
Bravi
Stefano
S
Cortesi
Enrico
E
Carlini
Paolo
P
Bracci
Raffaella
R
Tomao
Silverio
S
Messerini
Luca
L
Arcangeli
Annarosa
A
Torri
Valter
V
Bilancia
Domenico
D
Floriani
Irene
I
Tonato
Maurizio
M
Dinota
Angelo
A
Strafiuso
Gennaro
G
Corgna
Enrichetta
E
Porrozzi
Stella
S
Boni
Corrado
C
Rondini
Ermanno
E
Giunta
Alessandro
A
Monzio Compagnoni
Barbara
B
Biagioni
Franco
F
Cesari
Maurizio
M
Fornarini
Giuseppe
G
Nelli
Fabrizio
F
Carboni
Manlio
M
Cognetti
Francesco
F
Enzo
Maria Ruggeri
MR
Piga
Andrea
A
Romiti
Adriana
A
Olivetti
Alessandra
A
Masoni
Luigi
L
De Stefanis
Marinella
M
Dalla Mola
Angelo
A
Camera
Salvatore
S
Recchia
Francesco
F
De Filippis
Sandro
S
Scipioni
Loreto
L
Zironi
Sandra
S
Luppi
Gabriele
G
Italia
Maurizio
M
Banducci
Stefano
S
Pisani Leretti
Andrea
A
Massidda
Bruno
B
Ionta
Maria Teresa
MT
Nicolosi
Angelo
A
Canaletti
Rodolfo
R
Biscottini
Bruno
B
Grigniani
Fausto
F
Di Costanzo
Federica
F
Rovei
Rossella
R
Croce
Enrico
E
Carroccio
Rosalia
R
Gilli
Germana
G
Cavalli
Carla
C
Olgiati
Angelo
A
Pandolfi
Umberto
U
Rossetti
Riccardo
R
Natalini
Giovanni
G
Foa
Paolo
P
Oldani
Sabina
S
Bruno
Lorenzo
L
Cascinu
Stefano
S
Catalano
Giuseppina
G
Catalano
Vincenzo
V
Lungarotti
Ferdinando
F
Farris
Antonio
A
Sarobba
Maria Giuseppina
MG
Trignano
Mario
M
Muscogiuri
Antonio
A
Francavilla
Fontana
F
Figoli
Franco
F
Leoni
Maurizio
M
Papiani
Giorgio
G
Orselli
Gianfranco
G
Antimi
Mauro
M
Bellini
Vincenzo
V
Cabassi
Alessandro
A
Contu
Antonio
A
Pazzola
Antonio
A
Frignano
Mario
M
Lastraioli
Elena
E
Saggese
Matilde
M
Bianchini
Diletta
D
Antonuzzo
Lorenzo
L
Mela
Micol
M
Camisa
Roberta
R
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005743:Gastrectomy / Q000379:methods; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007150:Immunohistochemistry; D007558:Italy; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000139:chemically induced; D009367:Neoplasm Staging; D010349:Patient Compliance; D011379:Prognosis; D016016:Proportional Hazards Models; D013274:Stomach Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
D014408:Biomarkers, Tumor; D015251:Epirubicin; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil