Hspc-sparing treatments for rb-positive abnormal cellular proliferation

Abstract

This invention is in the area of improved compounds for and methods of treating selected RB-positive cancers and other Rb-positive abnormal cellular proliferative disorders while minimizing the deleterious effects on healthy cells, for example healthy Hematopoietic Stem Cells and Progenitor Cells (HSPCs), associated with current treatment modalities. In one aspect, improved treatment of select RB-positive cancers is disclosed using specific compounds disclosed herein. In certain embodiments, the compounds described herein act as highly selective and, in certain embodiments, short, transiently-acting cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors when administered to subjects.

What is claimed is: 
     
         1 .- 16 . (canceled) 
     
     
         17 . A method for treating retinoblastoma (Rb)-positive uterine cancer in a human comprising administering to the human an effective amount of a selective cyclin dependent kinase 4/6 (CDK4/6) inhibitor compound of structure: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein the CDK4/6 inhibitor is administered to the human at least once a day for 24 or more continuous days. 
     
     
         18 . The method of  claim 17 , wherein the selective CDK4/6 inhibitor is administered orally. 
     
     
         19 . The method of  claim 17 , wherein the selective CDK4/6 inhibitor is administered to the human at least once a day for 28 or more continuous days. 
     
     
         20 . The method of  claim 17 , wherein the selective CDK4/6 inhibitor is administered to the human at least once a day for 35 or more continuous days. 
     
     
         21 . The method of  claim 17 , wherein the selective CDK4/6 inhibitor is administered to the human twice a day. 
     
     
         22 . The method of  claim 19 , wherein the selective CDK4/6 inhibitor is administered to the human twice a day. 
     
     
         23 . The method of  claim 20 , wherein the selective CDK4/6 inhibitor is administered to the human twice a day. 
     
     
         24 . The method of  claim 17 , further comprising administering to the human at least one chemotherapeutic agent. 
     
     
         25 . The method of  claim 24 , wherein the chemotherapeutic agent is selected from the group consisting of anastrozole, carboplatin, cisplatin, docetaxel, doxorubicin, everolimus, ifosfamide, goserelin, letrozole, leuprolide acetate, medroxyprogesterone acetate, megestrol acetate, paclitaxel, ridaforolimus, tamoxifen, temsirolimus, toremifene, trastuzumab, and a combination thereof. 
     
     
         26 . The method of  claim 25 , wherein the chemotherapeutic agent is tamoxifen. 
     
     
         27 . The method of  claim 25 , wherein the chemotherapeutic agent is letrozole. 
     
     
         28 . A method for treating retinoblastoma (Rb)-positive endometrial cancer in a human comprising administering to the human an effective amount of a selective cyclin dependent kinase 4/6 (CDK4/6) inhibitor compound of structure: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein the CDK4/6 inhibitor is administered to the human at least once a day for 24 or more continuous days. 
     
     
         29 . The method of  claim 28 , wherein the selective CDK4/6 inhibitor is administered orally. 
     
     
         30 . The method of  claim 28 , wherein the selective CDK4/6 inhibitor is administered to the human at least once a day for 28 or more continuous days. 
     
     
         31 . The method of  claim 28 , wherein the selective CDK4/6 inhibitor is administered to the human at least once a day for 35 or more continuous days. 
     
     
         32 . The method of  claim 28 , wherein the selective CDK4/6 inhibitor is administered to the human twice a day. 
     
     
         33 . The method of  claim 30 , wherein the selective CDK4/6 inhibitor is administered to the human twice a day. 
     
     
         34 . The method of  claim 31 , wherein the selective CDK4/6 inhibitor is administered to the human twice a day. 
     
     
         35 . The method of  claim 28 , further comprising administering to the human at least one chemotherapeutic agent. 
     
     
         36 . The method of  claim 35 , wherein the chemotherapeutic agent is selected from the group consisting of anastrozole, carboplatin, cisplatin, docetaxel, doxorubicin, everolimus, ifosfamide, goserelin, letrozole, leuprolide acetate, medroxyprogesterone acetate, megestrol acetate, paclitaxel, ridaforolimus, tamoxifen, temsirolimus, toremifene, trastuzumab, and a combination thereof. 
     
     
         37 . The method of  claim 36 , wherein the chemotherapeutic agent is tamoxifen. 
     
     
         38 . The method of  claim 36 , wherein the chemotherapeutic agent is letrozole.