Treatment Of RB-Negative Tumors Using Topoisomerase Inhibitors In Combination With Cyclin Dependent Kinase 4/6 Inhibitors
This invention is in the area of improved therapeutic combinations for and methods of treating selected retinoblastoma (Rb)-negative cancers and Rb-negative abnormal cellular proliferative disorders using particular topoisomerase inhibitors and specific cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. In one aspect, the improved treatment of select Rb-negative cancers is disclosed using specific compounds disclosed herein in combination with a topoisomerase I inhibitor.
1 . A method for treating a host having triple negative breast cancer comprising administering an effective amount of a topoisomerase inhibitor selected from topotecan, etirinotecan pegol, belotecan, cositecan, and irinotecan and a CDK 4/6 inhibitor compound selected from:
or a pharmaceutically acceptable salt therein.
2 . The method of claim 1 , wherein the host is a human.
3 . The method of claim 2 , wherein the CDK 4/6 inhibitor compound is Compound Q or its pharmaceutically acceptable salt.
4 . The method of claim 2 , wherein the CDK 4/6 inhibitor compound is Compound T or its pharmaceutically acceptable salt.
5 . The method of claim 2 , wherein the CDK 4/6 inhibitor compound is Compound U or its pharmaceutically acceptable salt.
6 . The method of claim 2 , wherein the CDK 4/6 inhibitor compound is Compound GG or its pharmaceutically acceptable salt.
7 . The method of claim 2 , wherein the CDK 4/6 inhibitor compound is Compound X or its pharmaceutically acceptable salt.
8 . The method of claim 2 , wherein the CDK 4/6 inhibitor compound is Compound BB or its pharmaceutically acceptable salt.
9 . The method of claim 2 , wherein the at least one chemotherapeutic agent is topotecan.
10 . The method of claim 2 , wherein the at least one chemotherapeutic agent is irinotecan.
11 . The method of claim 2 , wherein the at least one chemotherapeutic agent is etirinotecan pegol.
12 . The method of claim 2 , wherein the at least one chemotherapeutic agent is belotecan.
13 . The method of claim 2 , wherein the at least one chemotherapeutic agent is cositecan.
14 . A method for treating a host having RB-negative cervical cancer comprising administering an effective amount of a chemotherapeutic agent selected from topotecan, etirinotecan pegol, belotecan, cositecan, and irinotecan and a CDK 4/6 inhibitor compound selected from:
or a pharmaceutically acceptable salt therein.
15 . The method of claim 14 , wherein the host is a human.
16 . The method of claim 15 , wherein the CDK 4/6 inhibitor compound is Compound Q or its pharmaceutically acceptable salt.
17 . The method of claim 15 , wherein the CDK 4/6 inhibitor compound is Compound T or its pharmaceutically acceptable salt.
18 . The method of claim 15 , wherein the CDK 4/6 inhibitor compound is Compound U or its pharmaceutically acceptable salt.
19 . The method of claim 15 , wherein the CDK 4/6 inhibitor compound is Compound GG or its pharmaceutically acceptable salt.
20 . The method of claim 15 , wherein the CDK 4/6 inhibitor compound is Compound X or its pharmaceutically acceptable salt.
21 . The method of claim 15 , wherein the CDK 4/6 inhibitor compound is Compound BB or its pharmaceutically acceptable salt.
22 . The method of claim 15 , wherein the at least one chemotherapeutic agent is topotecan.
23 . The method of claim 15 , wherein the at least one chemotherapeutic agent is irinotecan.
24 . A method for treating a host having small cell lung cancer comprising administering an effective amount of a chemotherapeutic agent selected from belotecan, etirinotecan pegol, and cositecan and a CDK 4/6 inhibitor compound selected from:
or a pharmaceutically acceptable salt therein.
25 . The method of claim 24 , wherein the host is a human.
26 . The method of claim 25 , wherein the CDK 4/6 inhibitor compound is Compound Q or its pharmaceutically acceptable salt.
27 . The method of claim 25 , wherein the CDK 4/6 inhibitor compound is Compound T or its pharmaceutically acceptable salt.
28 . The method of claim 25 , wherein the CDK 4/6 inhibitor compound is Compound U or its pharmaceutically acceptable salt.
29 . The method of claim 25 , wherein the CDK 4/6 inhibitor compound is Compound GG or its pharmaceutically acceptable salt.
30 . The method of claim 25 , wherein the CDK 4/6 inhibitor compound is Compound X or its pharmaceutically acceptable salt.
31 . The method of claim 25 , wherein the CDK 4/6 inhibitor compound is Compound BB or its pharmaceutically acceptable salt.
32 . The method of claim 25 , wherein the at least one chemotherapeutic agent is etirinotecan pegol.
33 . The method of claim 25 , wherein the at least one chemotherapeutic agent is belotecan.
34 . The method of claim 25 , wherein the at least one chemotherapeutic agent is cositecan.