Treatment of solid tumors with rapamycin derivatives

Abstract

The present invention is directed to the use of rapamycin derivatives for use in treating solid tumors, optionally in combination with a chemotherapeutic agent.

1 . A method for inhibiting growth of solid tumors of the breast in a subject having a solid breast tumor, said method comprising: administering to said subject a therapeutically effective amount of 40-O-(2-hydroxyethyl)-rapamycin, having the structure of a compound of formula I 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is CH 3 , 
         R 2  is —CH 2 —CH 2 —OH, and 
         X is ═O, 
         wherein said compound of formula I is adminstered concomitantly or sequentially with vinorelbine and trastuzumab. 
       
     
     
         2 . The method of  claim 1  wherein the solid tumor of the breast has metastasized. 
     
     
         3 . The method of  claim 1  wherein the compound of formula I is administered orally. 
     
     
         4 . The method of  claim 1  wherein the compound of formula I is administered at a daily dose range of from about 0.1 to 25 mg, as a single dose or in divided doses. 
     
     
         5 . The method of  claim 1  wherein the compound of formula I is administered in a unit dosage form of from about 0.05 to 12.5 mg. 
     
     
         6 . The method of  claim 5  wherein the compound of formula I is administered in a unit dosage form of from about 0.25 to 10 mg. 
     
     
         7 . The method of  claim 6  wherein the compound of formula I is administered in a unit dosage form of 10 mg. 
     
     
         8 . The method of  claim 1  wherein the trastuzumab is administered in a dosage range from about 1 to 4 mg/m 2 /week. 
     
     
         9 . The method of  claim 1  wherein the vinorelbine is administered in a dosage range from about 10 to 50 mg/m 2  day. 
     
     
         10 . A method for treating solid tumors of the breast in a subject having a solid breast tumor, said method comprising: administering to said subject a therapeutically effective amount of 40-O-(2-hydroxyethyl)-rapamycin, having the structure of a compound of formula I 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is CH 3 , 
         R 2  is —CH 2 —CH 2 —OH, and 
         X is ═O, 
         wherein said compound of formula I is adminstered concomitantly or sequentially with vinorelbine and trastuzumab. 
       
     
     
         11 . The method of  claim 10  wherein the solid tumor of the breast has metastasized. 
     
     
         12 . The method of  claim 10  wherein the compound of formula I is administered orally. 
     
     
         13 . The method of  claim 10  wherein the compound of formula I is administered at a daily dose range of from about 0.1 to 25 mg, as a single dose or in divided doses. 
     
     
         14 . The method of  claim 10  wherein the compound of formula I is administered in a unit dosage form of from about 0.05 to 12.5 mg. 
     
     
         15 . The method of  claim 14  wherein the compound of formula I is administered in a unit dosage form of from about 0.25 to 10 mg. 
     
     
         16 . The method of  claim 15  wherein the compound of formula I is administered in a unit dosage form of 10 mg. 
     
     
         17 . The method of  claim 10  wherein the trastuzumab is administered in a dosage range from about 1 to 4 mg/m 2 /week. 
     
     
         18 . The method of  claim 10  wherein the vinorelbine is administered in a dosage range from about 10 to 50 mg/m 2 day.