J A Ajani1, M Abramov2, I Bondarenko3, Y Shparyk4, V Gorbunova5, A Hontsa6, N Otchenash7, M Alsina8, S Lazarev9, J Feliu10, A Elme11, V Esko12, K Abdalla13, U Verma14, F Benedetti15, T Aoyama15, H Mizuguchi16, L Makris17, G Rosati18. 1. GI Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, USA. 2. State Institution Russian Scientific Oncology Centre n.a. N.N. Blokhin of RAMS, Moscow, Russia. 3. Oncology Department, Dnipropetrovsk Medical Academy, Clinical Hospital #4, Dnipropetrovsk, Ukraine. 4. Chemotherapy Department, Lviv State Oncology Regional Treatment and Diagnostic Centre Hospital, Lviv, Ukraine. 5. Chemotherapy Department, State Institution Russian Scientific Oncology Centre n.a. N.N. Blokhin of RAMS, Moscow, Russia. 6. Day Staing Department, Chernivtsi Regional Oncology Center, Chernivtsi. 7. Deparment of Oncology, Kharkiv Regional Clinical Oncology Center, Kharkiv, Ukraine. 8. Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain. 9. State Healthcare Institution 'Altai Regional Oncology Dispensary', Barnaul, Russia. 10. Department of Oncology, Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Hospital Universitario La Paz, Madrid, Spain. 11. Department of Oncology, North Estonian Regional Hospital, Harjumaa. 12. Cancer Center, East Tallinn Central Hospital, Tallinn, Estonia. 13. Department of Clinical Oncology, Fundaçaõ PIO XII - Hospital de Câncer de Barretos, Barretos, SP, Brazil. 14. Hematology/Oncology Department, University of Texas Southwestern Medical Center at Dallas, Dallas. 15. Departments of Clinical Development, Taiho Oncology Inc., Princeton. 16. Departments of Clinical Research, Taiho Oncology, Inc., Princeton. 17. Department of Oncology, Stathmi Inc., New Hope, USA. 18. Medical Oncology Unit, Ospedale San Carlo, Potenza, Italy.
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 0-1. 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. CLINICALTRIAL.GOV REGISTRATION NUMBER: NCT01285557.
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 0-1. 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. CLINICALTRIAL.GOV REGISTRATION NUMBER: NCT01285557.
Authors: Vincent T Janmaat; Ewout W Steyerberg; Ate van der Gaast; Ron Hj Mathijssen; Marco J Bruno; Maikel P Peppelenbosch; Ernst J Kuipers; Manon Cw Spaander Journal: Cochrane Database Syst Rev Date: 2017-11-28
Authors: Madoka Takeuchi; Jaffer A Ajani; Xuemin Fang; Per Pfeiffer; Masahiro Takeuchi; Hanneke W M van Laarhoven Journal: Cancers (Basel) Date: 2019-06-21 Impact factor: 6.639
Authors: Ahmed A Abdelhakeem; Xuemei Wang; Rebecca E Waters; Madhavi Patnana; Jeannelyn S Estrella; Mariela Blum Murphy; Allison M Trail; Yang Lu; Catherine E Devine; Naruhiko Ikoma; Prajnan Das; Brian D Badgwell; Jane E Rogers; Jaffer A Ajani Journal: Cancers (Basel) Date: 2021-01-23 Impact factor: 6.639