S-1 Oral Anticancer Agent Improves Patients' Survival In Adjuvant Gastric Cancer Trial Versus Surgery Alone

Results of the large randomised phase III study (ACTS-GC) announced at the 2007 Gastrointestinal Cancers Symposium in Orlando, USA, showed that the investigational oral anticancer agent S-1 reduced significantly the relative risk of death in early stage gastric cancer patients by a significant 32% as compared to curative surgery alone (p = 0.0024).

Based on the first interim efficacy analysis (N=1059) in June 2006, the study's data and safety monitoring committee (DSMC) recommended to the investigators that the study be stopped. The results (N= 1059) indicates that for all randomized patients overall survival at 3-years was 80.5% for patients receiving S-1 and 70.1% for patients undergoing surgery alone, with a hazard ratio (HR) of 0.68 (95%CI, 0.52-0.87, p=0.0024). The most common grade 3 or 4 adverse reactions for nausea, vomiting, diarrhea, anorexia and hematological reactions were below or equal to 6%.

The Steering Committee of the GI Symposium has granted a Public Health Exception for the S-1 abstract. In the case of a Public Health Exception, the research data should be made public as soon as possible so that physicians and patients may immediately begin to make treatment decisions based on the new information. This is applicable in the countries where the drug is approved.

This drug is currently in Phase III clinical development in the U.S. and not yet approved by the U.S. Food and Drug Administration.

About the ACTS-GC study

S-1 efficacy and safety was prospectively evaluated in a large randomized multicenter trial, which enrolled 1059 Japanese patients with early stage gastric cancer (stage II and III). This study was conducted in more than 100 medical institutions in Japan. Patients were randomly allocated to receive the oral S-1 anticancer agent for 12 months (80-120mg/day according to the body surface, 4 weeks administration with 2 weeks off in each course, starting within 45 days of surgery until 1 year after surgery,) versus curative surgery alone.

The primary study end-point was overall survival and the secondary endpoints were relapse free survival and safety. Both primary and secondary efficacy objectives of the study have been met. The reduction of the relative risk of relapse with S-1 was 38% (p < 0.0001). For all randomized patients, the 3 year relapse free survival was 72.2% in the S-1 arm and 60.1% for surgery alone (p=0.0001).

About S-1

S-1 is a novel oral fluorouracil anticancer product that combines 3 pharmacological agents: tegafur which is a pro-drug of 5 fluoro-uracil; gimeracil (5-chloro-2,4 dihydropyridine (CDHP)) which inhibits dihydropyrimidine dehydrogenase (DPD) enzyme activity; and oteracil (potassium oxonate (Oxo)) a gastrointestinal side effects corrector.

S-1 is currently used in Japan for the treatment of gastric, colorectal, head and neck, non-small cell lung, metastatic breast and pancreas cancers. In the United States, Europe and other countries, the product is in phase III clinical development.

Taiho commercializes and develops S-1 in Japan and few other countries in Asia, sanofi-aventis collaborates on the current clinical development and is leading the future clinical development and commercialization of the product in the United States, Europe, and other countries in the world, except certain Asian countries.

About Gastric Cancer

Gastric (or stomach) cancer is the 4th most common type of cancer worldwide with more than 934,000 new patients every year. It is also the second most common cause of cancer death worldwide; with more than 700,000 deaths annually. There were about 22,800 new cases of gastric cancer in the United States in 2005. In Europe, this number is over 143,000 patients.

About Taiho

Taiho Pharmaceutical Co., Ltd (Taiho) is a company engaged in discovery, development, manufacturing and marketing of pharmaceutical products, with headquarters in Tokyo, Japan.

Taiho is one of the leading companies focused on oncology. More information is available at the company's website at http://www.taiho.co.jp/english/index.html.

About sanofi-aventis

Sanofi-aventis is one of the world leaders in the pharmaceutical industry, ranking number one in Europe. Backed by a world-class R&D organisation, sanofi-aventis is developing leading positions in seven major therapeutic areas: cardiovascular, thrombosis, oncology, metabolic diseases, central nervous system, internal medicine and vaccines. Sanofi-aventis is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).

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