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Last Updated: March 29, 2024

Claims for Patent: 9,463,193


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Summary for Patent: 9,463,193
Title:Individual 5-fluorouracile dose optimization in folfiri treatment
Abstract: The present invention belongs to the field of improved personalized medicine. More precisely, the present invention relates to a method for progressively optimizing the 5-FU dose administered by continuous infusion in patients treated by a FOLFIRI regimen or a similar regimen, based on the 5-FU plasmatic concentration measured during the previous 5-FU continuous infusion and on a herein described decision algorithm. The present invention also relates to a method for treating a cancer patient in which the 5-FU dose administered in continuous infusion in each FOLFIRI or similar treatment cycle is optimized using the decision algorithm according to the invention.
Inventor(s): Gamelin; Erick (Bouchemaine, FR), Boisdron-Celle; Michele (Saint Leger Des Bois, FR), Morel; Alain (Juigne Sur Loire, FR)
Assignee: INSTITUT DE CANCEROLOGIE DE L\'OUEST (Angers, FR) UNIVERSITE D\'ANGERS (Angers, FR)
Application Number:13/121,103
Patent Claims:1. A method for treating a cancer patient in need thereof, said method comprising the steps of: a. determining from a blood sample of a patient suffering from cancer the dose D(n+1) of 5-fluorouracile (5-FU) for the next cycle of treatment (n+1), wherein each treatment cycle n comprises: 0-500 mg/m2 of 5-FU administered in a bolus, 0-600 mg/m2 of folinic acid or a salt thereof, a dose D(n) (in mg/m.sup.2) of 5-FU administered in a continuous infusion of 43 to 49 hours, and 0-500 mg/m.sup.2 of irinotecan; and said blood sample has been taken from said patient in previous treatment cycle n at least 1 hour after the beginning of the 5-FU perfusion and before the end of said perfusion, said method comprising: measuring in vitro the 5-FU plasmatic concentration in the blood sample calculating D(n+1) depending on D(n) using the following decision scheme: if [5-FU]<100 .mu.g/L, then D(n+1)=D(n).times.1.40, if 100<[5-FU]<200 .mu.g/L, then D(n+1)=D(n).times.1.30, if 200<[5-FU]<300 .mu.g/L, then D(n+1)=D(n).times.1.20, if 300<[5-FU]<400 .mu.g/L, then D(n+1)=D(n).times.1.10, if 400<[5-FU]<500 .mu.g/L, then D(n+1)=D(n).times.1.05, if 500<[5-FU]<600 .mu.g/L, then D(n+1)=D(n).times.1.025, if 600<[5-FU]<650 .mu.g/L, then D(n+1)=D(n), if 650<[5-FU]<700 .mu.g/L, then D(n+1)=D(n).times.0.975, if 700<[5-FU]<800 .mu.g/L, then D(n+1)=D(n).times.0.95, if 800<[5-FU]<900 .mu.g/L, then D(n+1)=D(n).times.0.90, if >900 [5-FU], then D(n+1)=D(n).times.0.80, and b. administering the dose D(n+1) calculated in step a) to the patient.

2. The method according to claim 1, wherein the duration of the continuous infusion of 5-FU in each cycle n is about 46 hours.

3. The method according to claim 1, wherein the dose of 5-FU administered in a bolus in each cycle n is about 400 mg/m.sup.2.

4. The method according to claim 1, wherein the dose of folinic acid or salt thereof administered to the patient in each cycle n is about 100 mg/m.sup.2.

5. The method according to claim 1, wherein the dose of irinotecan administered to the patient in each cycle n is comprised between 120 and 300 mg/m.sup.2.

6. The method according to claim 1, wherein the treatment further comprises the administration to the patient in each cycle n of an anticancer monoclonal antibody.

7. The method according to claim 6, wherein said anticancer monoclonal antibody is cetuximab, panitumumab or bevacizumab.

8. The method according to claim 1, wherein the blood sample has been taken in cycle n 15 minutes to 22 hours before the end of the 5-FU continuous infusion.

9. The method according to claim 8, wherein the blood sample has been taken in cycle n 2 to 3 hours before the end of the 5-FU continuous infusion.

10. The method according to claim 1, wherein the blood sample has been taken in cycle n between 1 hour and 5 hours after the beginning of the 5-FU continuous infusion.

11. The method according to claim 1, comprising pre-treatment diagnosis of a possible increased sensitivity of said patient to 5-FU, and wherein the 5-FU dose D(n) administered in a continuous infusion in cycle n is at most about 2500 mg/m.sup.2 and has been determined based on the pre-treatment diagnosis.

12. The method according to claim 11, wherein the diagnosis of a possible hypersensitivity of said patient to 5-FU is performed from at least one biological sample of said patient by combining at least two of the following in vitro tests: a) the analysis of the presence of a significant mutation in DPD gene, b) the measure of uracil plasmatic concentration, and c) the measure of the ratio dihydrouracil plasmatic concentrations/uracil plasmatic concentration (UH.sub.2/U ratio).

13. The method according to claim 12, wherein the three in vitro test have been performed and the initial dose D(n) has been determined using the following decision algorithm: a) If no significant mutation in DPD gene has been detected and uracil plasmatic concentration is less than 15 gg/L, or no significant mutation in DPD gene has been detected and uracil plasmatic concentration is at least 15 p.g/L but the UH2/U ratio is at least 6, then a standard dose D(n) of 2500 mg/m2 is administered to the patient in cycle n; b) In all other cases, if 6<UH2/U ratio, then D(n) is 1750 mg/m.sup.2 if 3<UH2/U ratio<6, then D(n) is 1250 mg/m.sup.2 if 1<UH2/U ratio<3, then D(n) is 750 mg/m.sup.2 if UH.sub.2/U ratio<1 then the patient is preferably not treated with 5-FU.

14. The method according to claim 1, wherein said patient is suffering from colorectal cancer, stomach cancer, hepatic ducts cancer, pancreas cancer, oesophagus cancer, or breast cancer.

Details for Patent 9,463,193

Applicant Tradename Biologic Ingredient Dosage Form BLA Approval Date Patent No. Expiredate
Eli Lilly And Company ERBITUX cetuximab Injection 125084 02/12/2004 ⤷  Try a Trial 2039-02-26
Eli Lilly And Company ERBITUX cetuximab Injection 125084 03/28/2007 ⤷  Try a Trial 2039-02-26
Genentech, Inc. AVASTIN bevacizumab Injection 125085 02/26/2004 ⤷  Try a Trial 2039-02-26
Amgen, Inc. VECTIBIX panitumumab Injection 125147 09/27/2006 ⤷  Try a Trial 2039-02-26
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

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