Map of Pancreatica Walks and Runs

Oral thymidylate synthase inhibitor as an Oral 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. 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.

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Dale O’Brien, MD

The Whipple Procedure in Elderly Patients with Pancreatic Cancer

One of the interesting aspects of the cutting edge of medicine and science as observed over the years is the pendulum swing as new discoveries are made and conclusions rendered, only later to become modified and placed in better context by further research.

A case in point is the increasing trend of research results that sanction the surgical treatment of older patients with pancreatic cancer. There are a number of studies in more recent times that indicate that the Whipple procedure (pancreaticoduodenectomy) can be used to good effect even for patients in their eighties. This is welcome news, as adenocarcinoma of the pancreas tends to be a disease of older patients.

Now comes a more cautionary study by Kosuge and colleagues from the National Cancer Center Hospital in Tokyo, as published this April in Langenbeck’s Archives of Surgery. These researchers compared the surgical and mortality outcomes of 22 patients older than 80 years of age with pancreatic cancer against those of a younger group.

They found that serious post-operative complication occurred in six of the elderly patients with this pancreatic cancer surgery, including an additional perioperative death of one of the elderly patients. These results were significantly worse than those of the younger group. Also, importantly the median survival of the older patients was only 13 months, compared with 82 months for the younger group.

The researchers suggest caution in the selection for pancreatic cancer surgery of patients who are older than 80 years of age.

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Dale O’Brien, MD

Gemzar PLUS Xeloda for Cancer of the Pancreas

An earlier blog entry (February 14th) referenced a study by UK researchers that suggested the substitution of the drug-agent capecitabine (Xeloda) in place of gemcitabine for the treatment of locally advanced pancreatic cancer.  Now comes another study by different UK researchers who looked at coupling gemcitabine together with Xeloda for the treatment of advanced pancreatic cancer.

Hubner and colleagues of the Christie NHS Foundation Trust, in Manchester, UK, in the April edition of the journalPancreas, have published the results of a study whereby the retrospectively reviewed the results of 113 patients with advanced cancer who were treated off-protocol with the combination regiment consisting of gemcitabine and capecitabine (GEMCAP).

They found that the GEMCAP combination appeared to be effective and importantly had reasonable side-effects – was generally tolerable. The researchers reference clinical trials that are additionally ongoing with this combination, and suggest that this off-label use appears reasonably consistent with what to date appears to be occurring in the early clinical trials results.

This combination appears worthy of further study and inquiry.

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Dale O’Brien, MD

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