News Release


Results of a Phase II Clinical Trial for the Novel Antitumor Agent TAS-102 Posted on the Electronic Edition of The Lancet Oncology (28/08/2012)

Taiho Pharmaceutical Co., Ltd. (HQ: Tokyo, President: Masayuki Kobayashi) announced today that the results of a Phase II clinical trial for the novel antimetabolic antitumor agent (compound) TAS-102 have been published in the electronic version of the cancer research journal The Lancet Oncology.

The Phase II clinical trial for TAS-102 was a randomized, double-blind study with a primary outcome measure of overall survival involving 172 patients with refractory metastatic colorectal cancer who had received standard chemotherapy of at least two or more regimens containing a fluoropyrimidine, irinotecan, and oxaliplatin. The results indicated that TAS-102 significantly improved overall survival compared with the placebo (overall survival median: 9.0 months vs. 6.6 months) and significantly reduced the risk of mortality (HR: 0.56, p=0.0011). Also, no instances of treatment-related mortality were reported. The most frequently reported adverse drug reaction with a CTCAE grade 3 or higher was neutropenia. Grade 3 or higher diarrhea, fatigue, nausea, and other adverse reactions were no more than 10%. The results of this Phase II clinical trial were announced at the 9th Annual Meeting of Japanese Society of Medical Oncology held in 2011.

TIn light of the results of this Phase II clinical trial of TAS-102, Taiho Pharmaceutical is currently proceeding with global Phase III clinical trials (RECOURSE) to further study the effects of TAS-102 on patients with unresectable, advanced refractory metastatic colorectal cancer who were unresponsive to standard chemotherapy treatments.

About TAS-102

TAS-102 is the world’s first fluorothymidine oral antitumor agent that successfully maintains an effective blood concentration of trifluorothymidine (FTD: α,α,α-trifluorothymidine). TAS-102 combines FTD and TPI (5-chloro-6-(2-iminopyrrolidin-1-yl)methyl-2,4(1H,3H) -pyrimidinedione hydrochloride), which inhibits thymidine phosphorylase. FTD disrupts a variety of DNA functions necessary for the proliferation of cancer cells by being efficiently incorporated into DNA.

About The Lancet Oncology

A leading medical journal in the field of oncology with an impact factor of 22.589 (2011).

See the July 22, 2011 news release for the results of the Phase II clinical trial.
English-language version:
Japanese-language version:

Summary of the Results of the TAS-102 Phase II Clinical Trial

Trial Name TAS-102 monotherapy for pretreated metastatic colorectal cancer: a double-blind, randomized, placebo-controlled Phase II trial
Background Novel treatments that confer survival benefit are needed in patients with metastatic colorectal cancer that was pretreated with standard treatments. Phase II clinical trials were conducted to determine the efficacy and safety of TAS-102, a novel fluorothymidine antitumor agent.
Methods The multicenter, double-blind, randomized, placebo-controlled Phase II clinical trial was conducted in Japan between August 25, 2009 and April 12, 2010. Eligible patients had a treatment history of two or more regimens of standard chemotherapy, and had metastatic colorectal cancer that was unresponsive or intolerant to fluoropyrimidine, irinotecan, and oxaliplatin (patients were 20 years or older, had to be able to take oral drugs, have measurable lesions, have an Eastern Cooperative Oncology Group performance status of between 0 and 2, and have adequate bone-marrow, hepatic, and renal functions).
The patients were randomly assigned at a rate of 2:1 into a TAS-102 group (administration of 35mg/m2 twice per day for five days with a two-day rest period of drug administration for a total of two weeks, and thereafter a 14-day rest period of drug administration) and a placebo group. Randomization was done using minimization. The allotment factor was performance status (PS). During the trial, the clinical investigator, patients, person in charge of analysis, and the trial sponsor were not advised of any information regarding the treatment assignment. The primary outcome measure was overall survival. The study is registered with the Japan Pharmaceutical Information Center, number japicCTI-090880.
Findings 112 patients allocated to the TAS-102 group and 57 allocated to the placebo group comprised the intention-to-treat population. Median follow-up was 11.3 months (IQR: 10.7-14.0). Median overall survival was 9.0 months (95% CI: 7.3-11.3) in the TAS-102 group, and 6.6 months (95% CI: 4.9-8.0) in the placebo group (hazard ratio for death: 0.56, 80% CI: 0.44-0.71, 95% CI: 0.39-0.81; p=0.0011). The numbers of patients with adverse drug reactions (ADR) of grade 3 or 4 were as follows: 57 (50%) of 113 patients given TAS-102 in the safety population had neutropenia, 32 (28%) had leucopenia, and 19 had (17%) anaemia. No patient given the placebo had grade 3 or worse neutropenia or leucopenia; three (5%) of 57 had grade 3 or worse anaemia. Serious adverse events occurred in 21 (19%) patients in the TAS-102 group and in five (9%) in the placebo group. No treatment-related deaths occurred.
Interpretation TAS-102 has promising efficacy and a manageable safety profile in patients with metastatic colorectal cancer who are refractory or intolerant to standard chemotherapies.

Lancet Oncology. August 28, 2012; DOI: 10.1016/ S1470-2045(12)70345-5

TAS-102 monotherapy for pretreated metastatic colorectal cancer: a double-blind, randomised, placebo-controlled phase 2 trial

Takayuki Yoshino, Nobuyuki Mizunuma, Kentaro Yamazaki, Tomohiro Nishina, Yoshito Komatsu, Hideo Baba, Akihito Tsuji, Kensei Yamaguchi, Kei Muro, Naotoshi Sugimoto, Yasushi Tsuji, Toshikazu Moriwaki, Taito Esaki, Chikuma Hamada, Takanori Tanase, Atsushi Ohtsu

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