639P - A phase II study of TAS-102 for advanced/recurrent esophageal cancer refractory/intolerable to standard therapies.

Date 09 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Drug Development
Oesophageal Cancer
Gastrointestinal Cancers
Presenter Takashi Kojima
Citation Annals of Oncology (2017) 28 (suppl_5): v209-v268. 10.1093/annonc/mdx369
Authors T. Kojima1, H. Kasai2, T. Tsushima3, H. Hara4, Y. Mori5, R. Ishihara6, K. Kato7, S. Hironaka8, K. Mukai2, O. Kikuchi5, K. Enomoto2, H. Tada2, R. Uozumi2, A. Kawaguchi9, M. Muto5
  • 1Department Of Gastroenterology And Gastrointestinal Oncology, National Cancer Center Hospital East, 277-8577 - Chiba/JP
  • 2Institute For Advancement Of Clinical And Translational Science (iact), Kyoto University Hospital, Kyoto/JP
  • 3Division Of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka/JP
  • 4Department Of Gastroenterology, Saitama Cancer Center, Saitama/JP
  • 5Department Of Therapeutic Oncology, Kyoto University Hospital, Kyoto/JP
  • 6Department Of Gastrointestional Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka/JP
  • 7Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 8Clinical Trial Promotion, Chiba Cancer Center Hospital, 260-8717 - Chiba/JP
  • 9Center For Comprehensive Community Medicine, Faculty Of Medicine, Saga University, Saga/JP



There is no effective chemotherapy for patients with esophageal squamous cell carcinoma (ESCC) refractory or intolerant to 5-FU, platinum, and taxanes. TAS-102 is an oral combination drug of trifluridine and tipiracil hydrochloride. Our preclinical study showed that TAS-102 has antitumor activity against 5-FU resistant esophageal cancer cells. We conducted this study to evaluate the safety and efficacy of TAS-102 in ESCC patients who were refractory or intolerant to standard treatment (UMIN000019268).


Patients with histologically proven advanced or recurrent ESCC, which had been refractory or intolerable to 5-FU, platinum, and taxanes, were eligible. Patients also had to satisfy following criteria: >20 years of age; ECOG performance status 0 or 1; adequate organ functions. TAS-102, 35 mg/m2 bid, was administered on days 1-5 and 8-12 for the first 2 weeks followed by 2-week rest. The regimen was repeated every 4 weeks until disease progression, serious adverse event, or refusal. Primary endpoint was progression-free survival rate at 3 months (PFS3). With expected PFS3 of 25% to 30% and the null hypothesis of 10% under 80% power and a one-sided significance level of 5%, 35 patients was needed.


A total of 42 patients were enrolled. 90% of the patients were male, 95% had distant metastasis, and 98% had target lesion (s). As of data cutoff, 34 events were observed. PFS3 was 15.4% (90% CI: 7.4%, 26.0%), which did not reject the null hypothesis. Median PFS and OS were 1.3 months and 4.5 months, respectively. Response rate was 0%, although 24% (10/42) of patients achieved stable disease. There were 3 patients not evaluable for response. Major treatment related adverse events of grade ≧3 were: neutrophil count decreased (48%), febrile neutropenia (7%), and appetite decreased (5%). No treatment related death was observed.


TAS-102 was feasible and showed modest efficacy in patients with refractory ESCC.

Clinical trial identification

UMIN000019268, 2015/10/13

Legal entity responsible for the study

Kyoto University Hospital


Taiho Pharmaceutical Co. Ltd.


T. Kojima: Corporate-sponsored research (to institution): Onoyakuhin, Shionogiseiyaku, MSD, Taihouyakuhin, Merukuserono, AstraZeneca. T. Tsushima: Takeda, Chugai Pharma, Taiho Pharmaceutical. H. Hara: AstraZeneca, Chugai Pharma, Merck Serono, MSD, Ono Pharmaceutical, Taiho. Pharmaceutical, Takeda, Boehringer Ingelheim, Dainippon Sumitomo Pharma, Daiichi-Sankyo. K. Kato: ONO Phaumaceticals, MSD, Sionogi, Merck Serono. M. Muto: Olympus, Mitsui Knowledge Industry, Taiho Pharmaceutical, Chugai Pharma, Theravalues Corporation, Pfizer. All other authors have declared no conflicts of interest.