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Oral Thymidylate Synthase Inhibitor as an Alternative to Gemcitabine?

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 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 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.  And 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.

More here


Dale O’Brien, MD


Overcoming Gemcitabine Resistance – Dasatinib

The drug agent gemcitabine has been the mainstay of the medical treatment of pancreatic cancer (ductal adenocarcinoma of the pancreas).  This assertion has perhaps been challenged by extensive 5-FU combinations in the past couple of years, but is still mostly held to be true by clinicians.

The wide adoption of the use of gemcitabine since 1997 has also engendered a question, why does it ultimately fail?  The thought is that resistance to gemcitabine occurs – which then allows the tumor to overpower the effects of the drug.

Now comes a Phase I study by Kurzrock and colleagues at MD Anderson Cancer Center / University of Texas (Houston) that pairs (together with gemcitabine) the leukemia drug dasatinib, which has shown in pre-clinical studies to help overcome resistance to gemcitabine.

Two of eight of the patients with pancreatic cancer either showed stable disease for more than six months or showed a partial response during the treatment.

It is an early study, but perhaps a useful approach to begin to discover methods to extend the benefit of one of the key drugs used in the treatment of pancreatic cancer.

More here


Dale O’Brien, MD .

America’s Finest City Half Marathon & 5K !

America’s Finest City Half Marathon & 5K in San Diego is just a month away!

Who’s participating in this awesome event?

Check it out here or if you can’t be a part of this one, sign up for one of the many others or even to dedicate-a-race!

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