A phase III trial comparing oral S-1/cisplatin and intravenous 5-fluorouracil/cisplatin in patients with untreated diffuse gastric cancer
Mené sur 361 patients atteints d'un cancer diffus de l'estomac, cet essai de phase III compare l'efficacité, du point de vue de la survie globale, et la toxicité d'un traitement dispensé par voie orale combinant S-1 et cisplatine et d'un traitement par voie intraveineuse combinant 5-fluorouracile et cisplatine en traitement de première ligne
Background The effect of histology-based treatment regimen on diffuse gastric adenocarcinoma has not been evaluated in clinical trials. This international phase III trial evaluated the efficacy and safety of S-1 (a contemporary oral fluoropyrimidine)/cisplatin versus 5-fluorouracil (5-FU)/cisplatin in chemotherapy-naïve patients with diffuse type adenocarcinoma involving the gastroesophageal junction or stomach. Patients and methods Eligibility criteria included untreated, measurable, advanced diffuse adenocarcinoma confirmed by central pathology and performance status of 0 to 1. Patients were randomized (2:1) to receive S-1/cisplatin or 5-FU/cisplatin. Primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS), time to treatment failure (TTF), overall response rate (ORR), and safety. A multivariable analysis was also performed. Results Overall, 361 patients were randomized (S-1/cisplatin, n=239; 5-FU/cisplatin, n=122); half (51%) were men, and median age was 56.0 years. In each group, median number of treatment cycles per patient was 4 (range, S-1/cisplatin: 1 to 20; 5-FU/cisplatin: 1 to 30), and dose intensity was >95%. OS was not different in the 2 groups (median OS with S-1/cisplatin, 7.5 [95% confidence interval (CI): 6.7, 9.3]; 5-FU/cisplatin, 6.6 [95% CI: 5.7, 8.1] months; hazard ratio [HR], 0.99 [95% CI: 0.76, 1.28]; P = .9312). ORR was significantly higher in the S-1/cisplatin than 5-FU/cisplatin group (34.7% vs 19.8%; P = .01), but PFS and TTF were not different. Safety was similar between the 2 groups; however, fewer patients treated with S-1/cisplatin than 5-FU/cisplatin had ≥1 Grade 3/4 treatment-emergent adverse event or ≥ 1 adverse event resulting in treatment discontinuation. One treatment-related death occurred in each group. Slow accrual led to early termination. Conclusions These data suggest that S-1/cisplatin and 5-FU/cisplatin are similar in efficacy and safety in untreated patients with advanced diffuse adenocarcinoma of the gastroesophageal junction or stomach. The primary endpoint was not met. ClinicalTrial.gov registration number NCT01285557