Method and composition for the treatment of cancer

Abstract

We have discovered that the administration of a G1 and/or S phase drug such as β-lapachone in combination with a G2/M drug such as a taxane derivative such as paclitaxel resulted in a unexpected greater than additive (i.e., synergistic) reduction in the number of tumors (and tumor volume) as compared with the administration of these agents alone. In addition, no signs of toxicity or weight loss were observed. The present invention relates to a method for treating a mammalian tumor using combinations such as a taxane derivative, preferably paclitaxel, and a β-lapachone, or a derivative or analog thereof.

1 - 14 . (canceled)  
     
     
         15 . A method of treating a solid tumor or tumors in a mammal in need thereof, the method comprising: 
 a) administering to the mammal an effective amount of a first compound comprising β-lapachone as the active ingredient; and    b) administering to the mammal an effective amount of a G2/M phase drug.    
     
     
         16 . The method of  claim 15 , wherein the G2/M phase drug is selected from the group consisting of microtubule targeting and topoisomerase poison drugs.  
     
     
         17 . The method of  claim 16 , wherein the microtubule targeting drug is selected from the group consisting of paclitaxel, docetaxel, vincristin, vinblastin, nocodazole, epothilones and navelbine.  
     
     
         18 . The method of  claim 16 , wherein the topoisomerase poison drug is selected from the group consisting of teniposide, etoposide, adriamycin, camptothecin, daunorubicin, dactinomycin, mitoxantrone, amsacrine, epirubicin and idarubicin.  
     
     
         19 . The method of  claim 15 , wherein the G2/M phase drug is a taxane derivative.  
     
     
         20 . The method of  claim 19 , wherein the taxane derivative is paclitaxel.  
     
     
         21 . The method of  claim 15 , wherein the G2/M phase drug is administered after the first compound.  
     
     
         22 . The method of  claim 15 , wherein the G2/M phase drug is administered within about 24 hours after the first compound is administered.  
     
     
         23 . The method of  claim 20 , wherein the paclitaxel is administered intravenously.  
     
     
         24 . The method of  claim 20 , wherein the paclitaxel is administered intravenously after administration of the first compound.  
     
     
         25 . The method of  claim 15 , wherein the solid tumor or tumors in the mammal are formed as the result of melanoma.  
     
     
         26 . The method of  claim 15 , wherein the solid tumor or tumors in the mammal are formed as the result of colon cancer.  
     
     
         27 . The method of  claim 15 , wherein the solid tumor or tumors in the mammal are formed as the result of prostate cancer.  
     
     
         28 . The method of  claim 15 , wherein the solid tumor or tumors in the mammal are formed as the result of lung cancer.  
     
     
         29 . The method of  claim 15 , wherein the solid tumor or tumors in the mammal are formed as the result of pancreatic cancer.  
     
     
         30 . The method of  claim 15 , wherein the solid tumor or tumors in the mammal are formed as the result of ovarian cancer.  
     
     
         31 . The method of  claim 15 , wherein the solid tumor or tumors in the mammal are formed as the result of breast cancer.  
     
     
         32 . A pharmaceutical composition comprising β-lapachone and paclitaxel and a pharmaceutically acceptable carrier.