Combination of cisplatin/S-1 in the treatment of patients with advanced gastric or gastroesophageal adenocarcinoma: Results of noninferiority and safety analyses compared with cisplatin/5-fluorouracil in the First-Line Advanced Gastric Cancer Study.

Abstract

BACKGROUND:

The aim of developing oral fluorouracil (5-FU) is to provide a more convenient administration route with similar efficacy and the best achievable tolerance. S-1, a novel oral fluoropyrimidine, was specifically designed to overcome the limitations of intravenous fluoropyrimidine therapies.

PATIENTS AND METHODS:

A multicentre, randomised phase 3 trial was undertaken to compare S-1/cisplatin (CS) with infusional 5-FU/cisplatin (CF) in 1053 patients with untreated, advanced gastric/gastroesophageal adenocarcinoma. This report discusses a post-hoc noninferiority overall survival (OS) and safety analyses.

RESULTS:

Results (1029 treated; CS = 521/CF = 508) revealed OS in CS (8.6 months) was statistically noninferior to CF (7.9 months) [hazard ratio (HR) = 0.92 (two-sided 95% confidence interval (CI), 0.80-1.05)] for any margin equal to or greater than 1.05. Statistically significant safety advantages for the CS arm were observed [G3/4 neutropenia (CS, 18.6%; CF, 40.0%), febrile neutropenia (CS, 1.7%; CF, 6.9%), G3/4 stomatitis (CS, 1.3%; CF, 13.6%), diarrhoea (all grades: CS, 29.2%; CF, 38.4%) and renal adverse events (all grades: CS, 18.8%; CF, 33.5%)]. Hand-foot syndrome, infrequently reported, was mainly grade 1/2 in both arms. Treatment-related deaths were significantly lower in the CS arm than the CF arm (2.5% and 4.9%, respectively; P<0.047).

CONCLUSION:

CS is noninferior to CF with a better safety profile and provides a new treatment option for patients with advanced gastric carcinoma.

• Authors: J A Ajani, M Buyse, M Lichinitser, V Gorbunova, G Bodoky, J Y Douillard, S Cascinu, V Heinemann, R Zaucha, A Carrato, D Ferry, V Moiseyenko
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 49 Issue 17 Pg. 3616-24 (Nov 2013) ISSN: 1879-0852 [Electronic] England
• PMID: 23899532 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Drug Combinations
• S 1 (combination)
• Tegafur
• Oxonic Acid
• Cisplatin
• Fluorouracil

Topics

• Adenocarcinoma (drug therapy, epidemiology, mortality)
• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Cisplatin (administration & dosage, adverse effects)
• Disease Progression
• Drug Combinations
• Esophageal Neoplasms (drug therapy, epidemiology, mortality)
• Female
• Fluorouracil (administration & dosage, adverse effects)
• Humans
• Male
• Middle Aged
• Neoadjuvant Therapy
• Oxonic Acid (administration & dosage, adverse effects)
• Stomach Neoplasms (drug therapy)
• Tegafur (administration & dosage, adverse effects)
• Young Adult