A phase III trial comparing oral S-1/cisplatin and intravenous 5-fluorouracil/cisplatin in patients with untreated diffuse gastric cancer

Abstract:

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

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