Abstract 2117
Background
S-1 is a commonly used agent in first line therapy of advanced gastric cancer in Japan. The recommended initial dose of S-1 is 120 mg/day for patients (pts) with a body surface area (BSA) of ≥ 1.5 m2 in Japan. Systemic exposure to 5-FU is significantly lower in Japanese cancer pts with a large BSA of ≥ 1.75 m2 who received the recommended fixed dose of S-1, as compared with those with a BSA of ≥ 1.50 m2 and <1.75 m2 (Ann Oncol 20: 946-949, 2009). However, there has been little knowledge of the relationship between survival and fixed dosing of S-1 in pts with large BSA.
Methods
Actual data from four randomized Japanese Phase III trials [START (S-1 vs S-1/docetaxel), SPIRITS (S-1 vs S-1/cisplatin), GC0301/TOP-002 (S-1 vs S-1/irinotecan), G-SOX (S-1+cisplatin vs S-1/oxaliplatin)] were combined to evaluate the effect of BSA on survival (OS) in terms of S-1 monotherapy and S-1 combination therapy. The pts were divided into two categories: those with BSA of ≥ 1.50 m2 and <1.75 m2 and those with a BSA of ≥ 1.75m2. The prognostic relevance of BSA was assessed using a multivariate proportional hazards model adjusted for the established clinical prognostic factors including age, performance status, tumor status, primary tumor, hematogenous metastasis, and peritoneal metastasis.
Results
A total of 1,246 pts were available in this analysis (S-1 monotherapy, n = 395; S-1 combination therapy, n = 851). The median OS for S-1 monotherapy and S-1 combination therapy was 11.7 and 13.6 months, respectively. In pts treated with S-1 monotherapy, OS was significantly shorter in those with a BSA of ≥ 1.75 m2, compared with those with a BSA of ≥ 1.5 m2 and <1.75m2 (HR 1.39; 95% CI 1.05-1.84; p = 0.02). However, OS was comparable in the two BSA categories for pts treated with S-1 combination (HR 1.09; 95% CI 0.90-1.34; p = 0.349). BSA was an independent prognostic factor in S-1 monotherapy (HR 1.33; 95% CI 0.999-1.77; p = 0.05) but not in S-1 combination therapy (HR 1.05; 95% CI 0.85-1.29; p = 0.65).
Conclusions
Although the fixed dosing of S-1 monotherapy affects the survival in pts with large BSA, combination therapy might overcome the worse prognosis even in those with large BSA.
Clinical trial identification
UMIN000019519.
Editorial acknowledgement
Legal entity responsible for the study
Japan Clinical Cancer Research Organization.
Funding
Has not received any funding.
Disclosure
W. Ichikawa: Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical Co. Ltd.; Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical Co. Ltd.; Honoraria (institution): Takeda Pharmaceutical Co.; Honoraria (self), Research grant / Funding (institution): Merck Serono; Honoraria (self): Bayer Yakuhin Ltd.; Research grant / Funding (institution): Ono Pharmaceutical Co. Ltd.; Research grant / Funding (institution): Shionogi Pharmaceutical Co. Ltd. Y. Sunakawa: Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Honoraria (institution): Taiho Pharmaceutical Co. Ltd; Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical Co. Ltd.; Honoraria (self), Research grant / Funding (institution): Yakult Honsha Co. Ltd.; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Takeda Pharmaceutical Co. Ltd.; Honoraria (self), Research grant / Funding (institution): Merck Serono; Honoraria (self): Bayer Yakuhin Ltd; Honoraria (self), Research grant / Funding (institution): Sanofi K.K.; Honoraria (self), Research grant / Funding (institution): Eli Lilly Japan; Research grant / Funding (institution): Daiichi Sankyo Pharmaceutical Co. Ltd.; Research grant / Funding (institution): MSD K.K.; Research grant / Funding (institution): Dainippon Sumitomo Pharmaceutical Co. Ltd.; Research grant / Funding (institution): Solasia Pharma K.K. K. Shitara: Honoraria (self): Novartis; Honoraria (self): AbbVie; Honoraria (self): Yakult; Honoraria (institution), Advisory / Consultancy: Astellas Pharma; Honoraria (institution), Advisory / Consultancy: Lilly; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Takeda; Advisory / Consultancy: Pfizer; Honoraria (institution), Advisory / Consultancy: Ono Pharmaceutical; Honoraria (institution), Advisory / Consultancy: MSD; Honoraria (institution): Dainippon Sumitomo Pharma; Honoraria (institution): Daiichi Sankyo; Honoraria (institution): Taiho Pharmaceutical; Honoraria (institution): Chugai Pharma; Honoraria (institution): Medi Science. K. Oba: Honoraria (self): Eisai Co., Ltd.; Honoraria (self): Chugai Pharmaceutical Co., Ltd.; Honoraria (self): Daiichi-Sankyo Pharmaceutical Co., Ltd.; Honoraria (self): Asahi Kasei Pharma Corp.; Advisory / Consultancy: Takeda Pharmaceuticals, Co., Ltd.; Advisory / Consultancy: Ono Pharmaceutical Co., Ltd. Y. Yamada: Honoraria (self): Taiho Pharmaceutical Co. Ltd.; Honoraria (self): Chugai Pharmaceutical Co. Ltd.; Honoraria (self): Nippon Kayaku; Honoraria (self): Eli Lilly; Honoraria (self): Ono Pharmaceutical Co. Ltd.; Honoraria (self): Bristol-Myers Squibb; Research grant / Funding (institution): Daiichi-Sankyo. Y. Sakata: Honoraria (self): Taiho Pharmaceutical Co. Ltd.; Advisory / Consultancy: Yakult Honsha. M. Takeuchi: Advisory / Consultancy: Hisamitsu Pharmaceutical; Advisory / Consultancy: Kowa; Advisory / Consultancy: Shionogi; Advisory / Consultancy: AbbVie. M. Fujii: Travel / Accommodation / Expenses: Taiho Pharmaceutical Co. Ltd.; Travel / Accommodation / Expenses: Japan Clinical Cancer Research Organization. All other authors have declared no conflicts of interest.
Resources from the same session
4304 - A user-friendly nomogram to predict relapse-free survival (RFS) in western patients with resected gastric cancer (GC)
Presenter: Massimiliano Salati
Session: Poster Display session 2
Resources:
Abstract
4546 - Efficacy and toxicity of weekly carboplatin and paclitaxel as induction or palliative treatment in advanced esophageal cancer patients
Presenter: Femke de Man
Session: Poster Display session 2
Resources:
Abstract
5908 - Perioperative chemotherapy with Docetaxel, Oxaliplatin, Fluorouracil and Leucovorin (FLOT) versus Epirubicin, Platinum and Capecitabine or Flourouracil (EOX/ECF) in Resectable Gastric or Gastroesophageal Junction Adenocarcinoma- Safety and response data from India.
Presenter: Tanuj Chawla
Session: Poster Display session 2
Resources:
Abstract
937 - Phase II Study of Preoperative Radiotherapy Combined with S-1 plus Cisplatin in Clinically Resectable Type 4 or Large Type 3 Gastric Cancer: OGSG1205
Presenter: Shunji Endo
Session: Poster Display session 2
Resources:
Abstract
1119 - Observational Study of the Peritoneal Washing Cytology Positive Gastric Cancer without Gross Peritoneal Metastasis Underwent Radical D2 Gastrectomy.
Presenter: Jun Eul Hwang
Session: Poster Display session 2
Resources:
Abstract
3744 - Primary results of multicenter phase II study of neoadjuvant chemotherapy with S-1 and oxaliplatin for locally advanced gastric cancer (Neo G-SOX PII)
Presenter: Akira Miki
Session: Poster Display session 2
Resources:
Abstract
5091 - Multicenter Phase I/II Feasibility Study of Adjuvant Treatment with S-1 in Patients after R0-Resection of Adenocarcinoma of the Stomach and Esophagogastric Junction (GMBH-STO-0114)
Presenter: Kathrin Heinrich
Session: Poster Display session 2
Resources:
Abstract
2891 - A phase I study of Docetaxel/Oxaliplatin/S-1 (DOS) combination neoadjuvant chemotherapy for patients with locally advanced adenocarcinoma of the esophagogastric junction
Presenter: Kei Hosoda
Session: Poster Display session 2
Resources:
Abstract
2994 - Apatinib combined with docetaxel in second-line treatment of advanced gastric cancer: a prospective clinical study (Data updated)
Presenter: Mudan Yang
Session: Poster Display session 2
Resources:
Abstract
3000 - A multicenter phase II study of TAS-114 in combination with S-1 in patients with pre-treated advanced gastric cancer (EPOC1604)
Presenter: Daisuke Takahari
Session: Poster Display session 2
Resources:
Abstract