S-1 seems to be seriously useful against a variety of tumors, & my remote research at Yale, on 5-azaorotic acid (pyrimidine antimetabolite, which he calls "Oxo") was cited in Shirakawa's original paper (misspelling my name "Grant" in the text, but correctly as "Granat" in the reference).
We had given it IV; he incorporated it as PO, leading to significant diminution of the side-effects of 5-FU.
I think we need that oral drug here in the US, for gastric & pancreatic cancer; & probably for colon, although it's fairly equivalent to Xeloda.
I did not continue in research or oncology, but became a practicing Family Physician, still in Private Practice, but very interested in what has become of my humble research years ago. And I have patients who I believe could benefit from the advantages of S-1.
I would especially like to hear from any of the Japanese original researchers.
Pepi Granat, MD
Pepi Granat, MD
Pepi:
You are right: meta-analytic data and systematic review have found it to be inferior to capecitabine (Xeloda), although with no superior survival ooutcomes, but with clinical relevant reduction in toxicity, especially HFS (hand-foot syndrome).
As to approval in the US: back in September 1999, the FDA's ODAC (Oncology Drug Advisory Committee) did review the clinical data on S-1 (in the form of UFT plus leucovorin) and voted unanimously to approve the drug application. (Note that S-1 is a combination of a prodrug of 5-FU, FTO, and two compounds, CDHP (5-chloro-2,4-dihydroxypyridine), aka "gimestat") and OXO (potassium oxonate), aka otastat.
But ODAC's parent, the FDA, continued to have concerns about approving either UFT alone or combined with leucovorin. Technically, at this date, the approvals of both UFT and the combination of UFT with leucovorin are on hold. But this is more mythology than reality: the company - Bristol-Myers Squibb (BMS) has to the present date declined to comment on or clarify its plans for, or the regulatory status, of S-1, and appears to have abandonned approval efforts in the United States. I would agreed with Matthew Herper's market analysis in Forbes that "Most American oncologists don’t think they’ll ever get their hands on UFT".
That is a loss for oncology patients in the Unites States, and I would speculate cautiously, that should additional mature data from comparative Phase III RCTs appear, especially in malignancies beyond just gastric, BMS may be prompted by material gain to reconsider reactivation of FDA approval.
Did you mean "non-inferior" above re: S-1 & capecitabine? (your first statement).
PG
Pepi:
You are quite right, yes "non-inferior" was intended, my typo.
Thank you for catching that.
Kind regards
Constantine