THERAPEUTIC REGIMENS FOR TREATMENT OF CANCER USING ERIBULIN AND SELECTIVE CDK4/6 INHIBITOR COMBINATIONS
The present invention provides methods and compositions for treating cancers with a combination of eribulin and a selective CDK4/6 inhibitor, wherein the selective CDK4/6 inhibitor reduces eribulin's effects on myelosuppression and/or myeloablation without reducing the efficacy of eribulin therapy.
1 . A method for treating cancer in a human comprising:
administrating to the human an effective amount of a selective CDK4/6 inhibitor; and
administering to the human an effective amount of eribulin, or a pharmaceutically acceptable salt thereof;
wherein the CDK4/6 inhibitor is administered 4 hours or less prior to administration of eribulin;
and wherein the selective CDK4/6 inhibitor is
or or a pharmaceutically acceptable salt thereof.
2 . The method of claim 1 , wherein the pharmaceutically acceptable salt of eribulin is eribulin mesylate.
3 . The method of claim 1 , wherein the cancer is selected from the group consisting of breast cancer, unresectable/metastatic liposarcoma, non-small cell lung cancer, prostate cancer, pancreatic cancer, colorectal cancer, bladder cancer, osteosarcoma, leiomyosarcoma, ovarian cancer, cervical cancer, colon cancer, head and neck cancer, sarcoma, relapsed/refractory rhabdomyosarcoma, non-rhabdomyosarcoma soft tissue sarcoma, Ewing sarcoma, angiosarcoma, epithelioid hemangioendothelioma, and urothelial cell cancer.
4 . The method of claim 3 , wherein the breast cancer is selected from the group consisting of metastatic breast cancer, triple-negative breast cancer, triple-positive breast cancer, HER2-negative breast cancer, HER2-positive breast cancer, estrogen receptor-positive breast cancer, estrogen receptor-negative breast cancer, progesterone receptor-positive breast cancer, progesterone receptor negative breast cancer, ductal carcinoma in situ (OCiS), invasive ductal carcinoma, invasive lobular carcinoma, inflammatory breast cancer, Paget disease of the nipple, phyllodes tumor, and a hormone responsive cancer.
5 . The method of claim 1 , wherein the cancer is a CDK4/6-replication dependent cancer.
6 . The method of claim 1 , wherein the cancer is a CDK4/6 replication independent cancer.
7 . The method of claim 1 , wherein the human is administered the CDK4/6 inhibitor about 30 minutes or less prior to administration of eribulin, or its pharmaceutically acceptable salt.
8 . The method of claim 1 , wherein the eribulin is administered on days 1 and 8 of a 21-day chemotherapeutic cycle, and the CDK4/6 inhibitor is administered on days 1 and 8 of a 21-day chemotherapeutic cycle.
9 . The method of claim 1 , wherein the eribulin is administered on days 1, 8, and 15 of a 28-day chemotherapeutic cycle, and the CDK4/6 inhibitor is administered on days 1, 8, and 15 of a 28-day chemotherapeutic cycle.
10 . The method of claim 4 , further comprising the administration of an anti-hormonal agent, wherein the anti-hormonal agent is selected from the group consisting of a SERM (selective estrogen receptor modulator), a SERD (selective estrogen receptor degrader), a complete estrogen receptor degrader, or another form of partial or complete estrogen antagonist, selective androgen receptor modulator, a selective androgen receptor degrader, a complete androgen receptor degrader, and another form of partial or complete androgen antagonist.
11 . The method of claim 10 , wherein the anti-hormonal agent is selected from the group consisting of fulvestrant, tamoxifen, anastrozole, letrozole, exemestane, goserelin, and leuprolide.
12 . A method for reducing myelosuppression in a human receiving eribulin for the treatment of a cancer comprising:
administrating to the human an effective amount of a selective CDK4/6 inhibitor; and
administering to the human an effective amount of eribulin, or a pharmaceutically acceptable salt thereof;
wherein the CDK4/6 inhibitor is administered 4 hours or less prior to administration of eribulin;
and wherein the selective CDK4/6 inhibitor is
or or a pharmaceutically acceptable salt thereof.
13 . The method of claim 12 , wherein the pharmaceutically acceptable salt of eribulin is eribulin mesylate.
14 . The method of claim 12 , wherein the cancer is selected from the group consisting of breast cancer, unresectable/metastatic liposarcoma, non-small cell lung cancer, prostate cancer, pancreatic cancer, colorectal cancer, bladder cancer, osteosarcoma, leiomyosarcoma, ovarian cancer, cervical cancer, colon cancer, head and neck cancer, sarcoma, relapsed/refractory rhabdomyosarcoma, non-rhabdomyosarcoma soft tissue sarcoma, Ewing sarcoma, angiosarcoma, epithelioid hemangioendothelioma, and urothelial cell cancer.
15 . The method of claim 14 , wherein the breast cancer is selected from the group consisting of metastatic breast cancer, triple-negative breast cancer, triple-positive breast cancer, HER2-negative breast cancer, HER2-positive breast cancer, estrogen receptor-positive breast cancer, estrogen receptor-negative breast cancer, progesterone receptor-positive breast cancer, progesterone receptor negative breast cancer, ductal carcinoma in situ (OCiS), invasive ductal carcinoma, invasive lobular carcinoma, inflammatory breast cancer, Paget disease of the nipple, phyllodes tumor, and a hormone responsive cancer.
16 . The method of claim 12 , wherein the cancer is a CDK4/6-replication dependent cancer.
17 . The method of claim 12 , wherein the cancer is a CDK4/6 replication independent cancer.
18 . The method of claim 12 , wherein the human is administered the CDK4/6 inhibitor about 30 minutes or less prior to administration of eribulin, or its pharmaceutically acceptable salt.
19 . The method of claim 12 , wherein the eribulin is administered on days 1 and 8 of a 21-day chemotherapeutic cycle, and the CDK4/6 inhibitor is administered on days 1 and 8 of a 21-day chemotherapeutic cycle.
20 . The method of claim 12 , wherein the eribulin is administered on days 1, 8, and 15 of a 28-day chemotherapeutic cycle, and the CDK4/6 inhibitor is administered on days 1, 8, and 15 of a 28-day chemotherapeutic cycle.
21 . The method of claim 15 , further comprising the administration of an anti-hormonal agent, wherein the anti-hormonal agent is selected from the group consisting of a SERM (selective estrogen receptor modulator), a SERD (selective estrogen receptor degrader), a complete estrogen receptor degrader, or another form of partial or complete estrogen antagonist, selective androgen receptor modulator, a selective androgen receptor degrader, a complete androgen receptor degrader, and another form of partial or complete androgen antagonist.
22 . The method of claim 21 , wherein the anti-hormonal agent is selected from the group consisting of fulvestrant, tamoxifen, anastrozole, letrozole, exemestane, goserelin, leuprolide, megestrol acetate and toremifene.