Antitumor agent
An antitumor agent containing, in combination, at least one kind of antitumor agent selected from the group consisting of an antitumor agent that forms a cross-link with DNA and shows an antitumor effect, an antimetabolite antitumor agent and a taxane antitumor agent, and a histone deacetylase inhibitor. According to the present invention, an antitumor agent causing reduced side effects and having a superior antitumor activity can be provided.
1 . A method of treating a subject comprising
administering to the subject
a histone deacetylase inhibitor in combination with
at least one kind of antitumor agent selected from the group consisting of an antitumor agent that forms a cross-link with DNA and shows an antitumor effect, an antimetabolite antitumor agent, and a taxane antitumor agent.
2 . The method of claim 1 , wherein the histone deacetylase inhibitor is a compound represented by the formula (I):
its reduction product, an analog, a prodrug or a pharmaceutically acceptable salt thereof.
3 . The method of claim 1 , wherein the histone deacetylase inhibitor is FK228 or a pharmaceutically acceptable salt thereof.
4 . The method of claim 1 , wherein the histone deacetylase inhibitor is SAHA or a pharmaceutically acceptable salt thereof.
5 . The method of claim 2 , wherein the antitumor agent that forms a cross-link with DNA and shows an antitumor effect is a platinum compound antitumor agent or an alkylating antitumor agent.
6 . The method of claim 5 , wherein the antitumor agent is cisplatin.
7 . The method of claim 2 , wherein the antimetabolite antitumor agent is 5-fluorouracil.
8 . The method of claim 2 , wherein the taxane antitumor agent is at least one of paclitaxel and docetaxel.
9 . The method of claim 1 , which comprises administering at least one antitumor agent for lung cancer, malignant lymphoma, cancer of digestive organ, breast cancer, ovarian cancer, musculoskeletal sarcoma, bladder cancer, leukemia, kidney cancer or prostate cancer.
10 . A method for enhancing the antitumor effect for at least one kind of antitumor agent selected from the group consisting of an antitumor agent that forms a cross-link with DNA and shows an antitumor effect, an antimetabolite antitumor agent and a taxane antitumor agent, which comprises:
administering a histone deacetylase inhibitor to a subject simultaneously with, or before or after administration of said antitumor agent.
11 . The method of claim 10 , wherein the histone deacetylase inhibitor is a compound represented by the formula (I)
its reduction product, analogs, prodrugs or a pharmaceutically acceptable salt thereof.
12 . The method of claim 10 , wherein the histone deacetylase inhibitor is FK228 or a pharmaceutically acceptable salt thereof.
13 . The method of claim 10 , wherein the histone deacetylase inhibitor is SAHA or a pharmaceutically acceptable salt thereof.
14 . The method of claim 11 , wherein the antitumor agent that forms a cross-link with DNA and shows an antitumor effect is a platinum compound antitumor agent or an alkylating antitumor agent.
15 . The method of claim 14 , wherein the antitumor agent is cisplatin.
16 . The method of claim 11 , wherein the antitumor agent is 5-fluorouracil.
17 . The method of claim 11 , wherein the antitumor agent is at least one of paclitaxel and docetaxel.
18 . The method of claim 10 , which is an antitumor effect enhancer for lung cancer, malignant lymphoma, cancer of digestive organ, breast cancer, ovarian cancer, musculoskeletal sarcoma, bladder cancer, leukemia, kidney cancer or prostate cancer.
19 . An antitumor agent comprising, in combination,
at least one kind of antitumor agent selected from the group consisting of an antitumor agent that forms a cross-link with DNA and shows an antitumor effect, an antimetabolite antitumor agent and a taxane antitumor agent, and
a histone deacetylase inhibitor.
20 . The antitumor agent of claim 19 , wherein the histone deacetylase inhibitor is a compound represented by the formula (I):
its reduction product, an analog, a prodrug or a pharmaceutically acceptable salt thereof.
21 . The antitumor agent of claim 20 , wherein the antitumor agent that forms a cross-link with DNA and shows an antitumor effect is a platinum compound antitumor agent or an alkylating antitumor agent.
22 . The antitumor agent of claim 21 , wherein the antitumor agent is cisplatin.
23 . The antitumor agent of claim 20 , wherein the antitumor agent is 5-fluorouracil.
24 . The antitumor agent of claim 20 , wherein the antitumor agent is at least one of paclitaxel and docetaxel.
25 . The antitumor agent of claim 19 , which is formulated as, or in a dosage suitable as, an antitumor agent for lung cancer, malignant lymphoma, cancer of digestive organ, breast cancer, ovarian cancer, musculoskeletal sarcoma, bladder cancer, leukemia, kidney cancer or prostate cancer.
26 . An antitumor effect enhancer for at least one kind of antitumor agent selected from the group consisting of an antitumor agent that forms a cross-link with DNA and shows an antitumor effect, an antimetabolite antitumor agent and a taxane antitumor agent, which comprises
a histone deacetylase inhibitor in a form or dosage suitable for enhancing said antitumor agent.
27 . The enhancer of claim 26 , wherein the histone deacetylase inhibitor is a compound represented by the formula (I):
its reduction product, analogs, prodrugs or a pharmaceutically acceptable salt thereof.
28 . The enhancer of claim 27 , wherein the antitumor agent that forms a cross-link with DNA and shows an antitumor effect is a platinum compound antitumor agent or an alkylating antitumor agent.
29 . The enhancer of claim 28 , wherein the antitumor agent is cisplatin.
30 . The enhancer of claim 27 , wherein the antitumor agent is 5-fluorouracil.
31 . The enhancer of claim 27 , wherein the antitumor agent is at least one of paclitaxel and docetaxel.
32 . The enhancer of claim 26 , which is formulated as, or in a dosage suitable as, an antitumor effect enhancer for lung cancer, malignant lymphoma, cancer of, digestive organ, breast cancer, ovarian cancer, musculoskeletal sarcoma, bladder cancer, leukemia, kidney cancer or prostate cancer.
33 . A commercial package comprising:
a concomitant agent comprising at least one kind of antitumor agent selected from the group consisting of an antitumor agent that forms a cross-link with DNA and shows an antitumor effect, an antimetabolite antitumor agent and a taxane antitumor agent, and
a written matter associated therewith, the written matter stating that the concomitant agent can or should be used as an antitumor agent.
34 . The commercial package of claim 33 , wherein the histone deacetylase inhibitor is a compound represented by the formula (I):
its reduction product, an analog, a prodrug or a pharmaceutically acceptable salt thereof.
35 . The commercial package of claim 34 , wherein the antitumor agent that forms a cross-link with DNA and shows an antitumor effect is a platinum compound antitumor agent or an alkylating antitumor agent.
36 . The commercial package of claim 35 , wherein the antitumor agent is cisplatin.
37 . The commercial package of claim 34 , wherein the antitumor agent is 5-fluorouracil.
38 . The commercial package of claim 34 , wherein the antitumor agent is at least one of paclitaxel and docetaxel.
39 . A commercial package comprising:
a preparation containing a histone deacetylase inhibitor and
a written matter associated therewith, the written matter stating that the preparation can or should be used for enhancing an antitumor effect of at least one kind of antitumor agent selected from the group consisting of an antitumor agent that forms a cross-link with DNA and shows an antitumor effect, an antimetabolite antitumor agent and a taxane antitumor agent.
40 . The commercial package of claim 39 , wherein the histone deacetylase inhibitor is a compound represented by the formula (I):
its reduction product, an analog, a prodrug or a pharmaceutically acceptable salt thereof.
41 . The commercial package of claim 40 , wherein the antitumor agent that forms a cross-link with DNA and shows an antitumor effect is a platinum compound ariLitumor agent or an alkylating antitumor agent.
42 . The commercial package of claim 41 , wherein the antitumor agent is cisplatin.
43 . The commercial package of claim 40 , wherein the antitumor agent is 5-fluorouracil.
44 . The commercial package of claim 40 , wherein the antitumor agent is at least one of paclitaxel and docetaxel.