THERAPEUTIC EFFECT PREDICTION METHOD FOR COLORECTAL CANCER PATIENT IN WHOM EXPRESSION OF TK1 PROTEIN HAS INCREASED

• US 20160082032A1
• Filed: 05/16/2014
• Published: 03/24/2016
• Est. Priority Date: 05/17/2013
• Status: Abandoned Application

• Current Assignee: Taiho Pharmaceutical Company Limited (Otsuka Holdings Company Limited), Taiho Pharmaceutical Co., Ltd.
• Original Assignee: Taiho Pharmaceutical Company Limited (Otsuka Holdings Company Limited)
• Inventors: SAKAMOTO, Kazuki, ITO, Masanobu
• Application Number:
  US14/891,395
• Publication Number:
  US 20160082032A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/513 having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• CPC Class Codes: A61K 31/7072 having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: G01N 2333/91205 Phosphotransferases in general
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/57419 of colon

Abstract

The present invention provides a method for predicting the therapeutic effect of chemotherapy using an antitumor agent containing trifluridine and tipiracil hydrochloride at a molar ratio of 1:0.5 on a colorectal cancer patient, the method comprising the following steps (1) to (3). As the means for solving the problem, the following invention is provided: a method comprising (1) detecting the expression of TK1 protein by an immunohistochemical method in tumor cells contained in a biological sample obtained from the patient; (2) based on the detection results obtained in step (1), classifying the tumor cells into positive cells and negative cells, and calculating the percentage of positive cells in the tumor cells; and (3) based on the calculation results obtained in step (2), predicting that when the percentage is 30% or more, the patient is likely to sufficiently respond to chemotherapy using the antitumor agent containing trifluridine and tipiracil hydrochloride at a molar ratio of 1:0.5.

Claims

1. A method for predicting a therapeutic effect of chemotherapy using an antitumor agent containing trifluridine and tipiracil hydrochloride at a molar ratio of 1:

0.5 on a colorectal cancer patient, the method comprising the following steps (1) to (3);

(1) detecting the expression of TK1 protein by an immunohistochemical method in tumor cells contained in a biological sample obtained from the patient;

(2) based on the detection results obtained in step (1), classifying the tumor cells into positive cells and negative cells, and calculating the percentage of positive cells in the tumor cells; and

(3) based on the calculation results obtained in step (2), predicting that when the percentage is 30% or more, the patient is likely to sufficiently respond to the chemotherapy using the antitumor agent containing trifluridine and tipiracil hydrochloride at a molar ratio of 1;

0.5.

2. The method according to claim 1, wherein the positive cells are evaluated as 2+ or 3+ based on staining intensity.

3. The method according to claim 1, wherein the colorectal cancer patient is refractory or intolerant to standard therapy.

4. An antitumor agent containing trifluridine and tipiracil hydrochloride at a molar ratio of 1:

0.5 for a colorectal cancer patient, wherein the patient is predicted to be likely to sufficiently respond to chemotherapy using the antitumor agent, by a method comprising the following steps (1) to (3);

(1) detecting the expression of TK1 protein by an immunohistochemical method in tumor cells contained in a biological sample obtained from the patient;

(2) based on the detection results obtained in step (1), classifying the tumor cells into positive cells and negative cells, and calculating the percentage of positive cells in the tumor cells; and

(3) based on the calculation results obtained in step (2), predicting that when the percentage is 30% or more, the patient is likely to sufficiently respond to the chemotherapy using the antitumor agent containing trifluridine and tipiracil hydrochloride at a molar ratio of 1;

0.5.

5. A kit for predicting a therapeutic effect of chemotherapy using an antitumor agent containing trifluridine and tipiracil hydrochloride at a molar ratio of 1:

0.5 on a colorectal cancer patient, the kit comprising an antibody that specifically recognizes TK1 protein as a reagent, wherein the therapeutic effect is predicted by the following steps (1) to (3);

(1) detecting the expression of TK1 protein by an immunohistochemical staining method in tumor cells contained in a biological sample obtained from the patient;

(2) based on the detection results obtained in step (1), classifying the tumor cells into positive cells and negative cells, and calculating the percentage of positive cells in the tumor cells; and

(3) based on the calculation results obtained in step (2), predicting that when the percentage is 30% or more, the patient is likely to sufficiently respond to the chemotherapy using the antitumor agent containing trifluridine and tipiracil hydrochloride at a molar ratio of 1;

0.5.

6. A method for treating a colorectal cancer patient comprising the following steps (1) to (4):

(1) detecting the expression of TK1 protein by an immunohistochemical staining method in tumor cells contained in a biological sample obtained from the patient;

(2) based on the detection results obtained in step (1), classifying the tumor cells into positive cells and negative cells, and calculating the percentage of positive cells in the tumor cells;

(3) based on the calculation results obtained in step (2), predicting that when the percentage is 30% or more, the patient is likely to sufficiently respond to chemotherapy using an antitumor agent containing trifluridine and tipiracil hydrochloride at a molar ratio of 1;

0.5; and

(4) administering the antitumor agent to the patient who is predicted to be likely to sufficiently respond to the chemotherapy in step (3).

7. An antitumor agent containing trifluridine and tipiracil hydrochloride at a molar ratio of 1:

0.5, wherein the antitumor agent is for use in the treatment of a colorectal cancer patient who is predicted to be likely to sufficiently respond to chemotherapy using the antitumor agent, by a method comprising the following steps (1) to (3);

(1) detecting the expression of TK1 protein by an immunohistochemical method in tumor cells contained in a biological sample obtained from the patient;

(2) based on the detection results obtained in step (1), classifying the tumor cells into positive cells and negative cells, and calculating the percentage of positive cells in the tumor cells; and

(3) based on the calculation results obtained in step (2), predicting that when the percentage is 30% or more, the patient is likely to sufficiently respond to the chemotherapy using the antitumor agent containing trifluridine and tipiracil hydrochloride at a molar ratio of 1;

0.5.