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Clinical Trial Results

Summaries of Newsworthy Clinical Trial Results
  • Posted: 03/12/2008

Stomach Cancer Drug, S-1, Shows Promise in Japanese Trial

Key Words

Stomach (gastric) cancer, S-1, cisplatin. (Definitions of many terms related to cancer can be found in the Dictionary.)


In this Japanese clinical trial, patients with advanced, inoperable stomach cancer who received combination therapy with cisplatin and a drug called S-1 lived about two months longer than patients treated with S-1 alone. S-1 is not currently approved for use in the United States. Because S-1 is broken down by the body differently in patients of European and Japanese descent, many U.S. patients may not be able to tolerate the doses of the drug given in this study.


Lancet Oncology, published March 2008 (see the journal abstract)
(Lancet Oncol. 2008 Mar;9(3):215-21. Epub 2008 Feb 20)


Stomach cancer (also known as gastric cancer) is relatively uncommon in the United States and other Western countries. Worldwide, however, it is the second leading cause of cancer deaths. Stomach cancer can be cured if the tumor is found early and completely removed surgically. However, the disease is often not diagnosed until it has already spread (metastasized) to other tissues and organs. Outcomes are very poor for patients with advanced stomach cancer that cannot be surgically removed.

A drug known as S-1 is used as a first-line treatment for stomach cancer in Japan. As yet, S-1 is not approved for use in the United States. Instead, U.S. doctors treat advanced stomach cancer with a drug called fluorouracil (5-FU). S-1 contains tegafur, a substance that in the body converts to 5-FU.

A potential advantage of S-1 over the drug 5-FU is that S-1 can be taken by mouth, whereas 5-FU must be given intravenously. A phase I/II study showed promising results when Japanese patients with advanced stomach cancer were treated with a combination of S-1 and a second drug called cisplatin, a commonly used cancer chemotherapy.

The Study

In this phase III study, 298 Japanese patients with advanced stomach cancer were assigned at random to treatment with either S-1 alone or S-1 plus cisplatin. All of the patients had disease that had spread to distant tissues and organs. The principal investigator for this study was Wasaburo Koizumi, M.D., of Kitasato University School of Medicine in Sagamihara, Japan. The full title of the study was “S-1 Plus cisplatin versus S-1 In RCT In the treatment for Stomach cancer,” or SPIRITS.


Patients in the SPIRITS trial were followed for a median of almost three years. Those who received S-1 plus cisplatin survived for a median of 13 months, compared with 11 months for their counterparts who were treated with S-1 alone. The combination therapy also delayed progression of disease for longer than S-1 alone (six months vs. four months).

Moderate to severe adverse effects of treatment such as anemia, anorexia, nausea, and a drop in white blood cell counts were more frequent in patients treated with S-1 plus cisplatin.


Studies have shown that the tegafur in S-1 is converted to 5-FU much more quickly in patients of European descent than in Japanese patients. For this reason, most patients in the United States may be unable to tolerate the doses of S-1 used in the SPIRITS trial, says John Jessup, M.D., of the National Cancer Institute’s (NCI) Division of Cancer Treatment and Diagnosis.


An ongoing large international phase III study, the First-Line Advanced Gastric Cancer Study (FLAGS), is comparing the effectiveness of S-1 plus cisplatin with that of 5-FU plus cisplatin. Preliminary results from FLAGS are expected in 2009. Any decision to approve S-1 for the treatment of patients with stomach cancer in the United States is likely to await the FLAGS results, says NCI's Jessup.

Jessup also notes that the drug capecitabine (Xeloda®), like S-1, is available in pill form and turns into 5-FU in the body. Capecitabine, approved in the U.S. for the treatment of colon and breast cancers, is currently being tested in the treatment of stomach and other cancers.