TY - JOUR
T1 - A phase III trial comparing oral S-1/cisplatin and intravenous 5-fluorouracil/cisplatin in patients with untreated diffuse gastric cancer
AU - The DIGEST Study Group
AU - Ajani, Jaffer A.
AU - Abramov, M.
AU - Bondarenko, I.
AU - Shparyk, Y.
AU - Gorbunova, V.
AU - Hontsa, A.
AU - Otchenash, N.
AU - Alsina, M.
AU - Lazarev, S.
AU - Feliu, J.
AU - Elme, A.
AU - Esko, V.
AU - Abdalla, K.
AU - Verma, U.
AU - Benedetti, F.
AU - Aoyama, T.
AU - Mizuguchi, H.
AU - Makris, L.
AU - Rosati, G.
AU - Aivado, Manuel
N1 - Funding Information:
The DIGEST study group would like to thank the patients, their families, all study teams/participants, and Manuel Aivado, MD, PhD, who previously contributed to this study. Funding for this study was provided by Taiho Oncology, Inc., Princeton, NJ, USA. The authors were responsible for all content and editorial decisions and received no honoraria related to the development of this publication. Dr Jaffer A. Ajani had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors contributed to the research, writing, and reviewing of all drafts of this publication. Since all the results were collected by the Sponsor Designee, the initial draft of the manuscript was prepared by the Sponsor in order to ensure that all the results are presented accurately. All authors approved the final draft. Editorial and medical writing support was provided by Cactus Communications Inc., supported by Taiho Oncology, Inc.
Publisher Copyright:
© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
PY - 2017/9
Y1 - 2017/9
N2 - 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 0-1. Patients were randomized (2: 1) to receive S-1/cisplatin or 5-FU/cisplatin. Primary end point was overall survival (OS), and secondary end points were progression-free survival, time to treatment failure, overall response rate, and safety. A multivariable analysis was also carried out. 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: 1-20; 5-FU/cisplatin: 1-30), and dose intensity was >95%. OS was not different in the two 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, 0.99 [95% CI: 0.76, 1.28]; P=0.9312). Overall response rate was significantly higher in the S-1/cisplatin than 5-FU/cisplatin group (34.7% versus 19.8%; P=0.01), but progression-free survival and time to treatment failure 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 end point was not met.
AB - 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 0-1. Patients were randomized (2: 1) to receive S-1/cisplatin or 5-FU/cisplatin. Primary end point was overall survival (OS), and secondary end points were progression-free survival, time to treatment failure, overall response rate, and safety. A multivariable analysis was also carried out. 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: 1-20; 5-FU/cisplatin: 1-30), and dose intensity was >95%. OS was not different in the two 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, 0.99 [95% CI: 0.76, 1.28]; P=0.9312). Overall response rate was significantly higher in the S-1/cisplatin than 5-FU/cisplatin group (34.7% versus 19.8%; P=0.01), but progression-free survival and time to treatment failure 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 end point was not met.
KW - 5-fluorouracil
KW - Cisplatin
KW - Diffuse gastric cancer
KW - Randomized trial
KW - S-1
KW - Sideeffect
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U2 - 10.1093/annonc/mdx275
DO - 10.1093/annonc/mdx275
M3 - Article
C2 - 28911091
AN - SCOPUS:85029883343
SN - 0923-7534
VL - 28
SP - 2142
EP - 2148
JO - Annals of Oncology
JF - Annals of Oncology
IS - 9
ER -