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Oral thymidylate synthase inhibitor as an Oral Alternative to Gemcitabine in Pancreatic Cancer?

Especially researchers in Japan have been studying the outcomes of the orally administered drug known as S-1 in the treatment of pancreatic cancer (ductal adenocarcinoma of the pancreas). S-1 is a fluorouracil drug agent (similar to 5FU – fluorouracil), which like 5-FU, functions as an inhibitor of thymidylate synthase. S-1 is comprised of three components: tegafur (a prodrug of 5-fluorouracil), 5-chloro-2,4-dihydroxypyridine, and potassium oxonate.

In the May 1st issue of the Journal of Clinical Oncology, the official publication of the American Society of Clinical Oncology, Tanaka and his Japanese colleagues from the National Cancer Center Hospital in Tokyo, reported out the results of a Phase 3 study that compared the combination of gemcitabine and S-1 against the use of S-1 alone, and the use of gemcitabine alone in patients with either locally advanced or advanced pancreatic cancer.

They recruited 834 patients with to the study, and found a median survival duration of 8.8 months in the pancreatic cancer patients receiving gemcitabine, 9.7 months in those receiving S-1, and 10.1 months in those receiving the combination regimen. There was found to be no significant statistical significance between the use of gemcitabine versus S-1 as monotherapy.  The combination gemcitabine plus S-1 arm of the study demonstrated more severe toxicity in patients, primarily hematologic and gastrointestinal side effects.

The researchers conclude that therapy with either gemcitabine or S-1 is comparable in locally advanced and advanced pancreatic cancer. This is an intriguing finding that certainly deserves further study.

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Dale O’Brien, MD