Methods for increasing blood plasma 2′-deoxyuridine (dUrd) and thymidylate synthase inhibition
AssigneeIsofol Medical AB
InventorsGöran U. Carlsson, Bengt Gustavsson, Elisabeth Odin, Yvonne Wettergren, Anders Vedin
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Abstract
The present invention provides methods for increasing plasma dUrd levels comprising the administration of 6R-MTHF. The methods of increasing plasma dUrd increase dUrd levels compared to equimolar concentrations of LV. The present invention also provides methods for increasing TS inhibition comprising the administration of 6R-MTHF. The present invention also provides methods for increasing TS inhibition comprising the administration of 6R-MTHF.
Claims16
A method of increasing plasma concentration of 2′-deoxyuridine (dUrd) in a human subject comprising:
- a. a step of administering 500 mg/m2 5-fluorouracil (5-FU) intravenously as a bolus injection to said human subject;
- b. following (a), a step of administering 30, 60, 120, or 240 mg/m2 [6R]-5, 10-methylene tetrahydrofolate (6R-MTHF) intravenously as one or more bolus injections to said human subject;
- and
- c. optionally administering a therapeutically effective amount of at least one anticancer agent selected from the group consisting of oxaliplatin, irinotecan, and bevacizumab;
- wherein said administration produces an increased plasma concentration of dUrd relative to dUrd plasma concentration in a human subject following administration of an equimolar dose of 5-formyl tetrahydrofolate (LV).
A method of inhibiting thymidylate synthase (TS) in a human subject comprising:
- a. a step of administering 500 mg/m2 5-FU intravenously as a bolus injection to said human subject;
- b. following (a), a step of administering 30, 60, 120, or 240 mg/m2 6R-MTHF intravenously as one or more bolus injections to said human subject;
- and
- c. optionally administering a therapeutically effective amount of at least one anticancer agent selected from the group consisting of oxaliplatin, irinotecan, and bevacizumab;
- wherein said administration produces an increased inhibition of TS relative to TS inhibition in a human subject following administration of an equimolar dose of LV.
Dependencies are inferred from the claim text.