Methods for modulating tumor growth and metastasis

Abstract

Methods and pharmaceutical compositions for modulating tumor growth or metastasis are provided.

1 . A method for modulating tumor growth or metastasis in an animal in need thereof, comprising sequential or simultaneous administration of carboplatin and a combretastatin A-4 phosphate prodrug salt in amounts effective therefor.  
     
     
         2 . A method for modulating tumor growth or metastasis in an animal in need thereof, comprising administration of a combretastatin A-4 phosphate prodrug salt and carboplatin, and in amounts effective therefore, wherein said combretastatin A-4 phosphate prodrug salt is administered in a time relative to administration of carboplatin sufficient to modulate blood flow to said tumor to provide a time-dependent effective tumor concentration of carboplatin.  
     
     
         3 . The method of  claim 1  or  2 , wherein said carboplatin is administered simultaneously with said combretastatin A-4 phosphate prodrug salt.  
     
     
         4 . The method of  claim 1  or  2 , wherein said carboplatin is administered at least 24 hours prior to said combretastatin A-4 phosphate prodrug salt.  
     
     
         5 . The method of  claim 1  or  2 , wherein said carboplatin is administered at least 3 hours prior to said combretastatin A-4 phosphate prodrug salt.  
     
     
         6 . The method of  claim 1  or  2 , wherein said carboplatin is administered within 24 hours after the administration of the combretastatin A-4 phosphate prodrug salt.  
     
     
         7 . The method of  claim 1  or  2 , wherein said carboplatin is administered within 3 hours after the administration of the combretastatin A-4 phosphate prodrug salt.  
     
     
         8 . The method of  claim 1  or  2 , wherein carboplatin comprises a unit dosage form between AUC 4 and AUC 6.  
     
     
         9 . The method of  claim 1  or  2 , wherein said combretastatin A-4 phosphate prodrug salt comprises a unit dosage form of between 45 and 63 mg/kg.  
     
     
         10 . The method of  claim 1  or  2 , wherein said method further comprises the administration of radiotherapy to the animal.  
     
     
         11 . The method of  claim 1  or  2 , wherein said tumor is selected from the group consisting of a melanoma, an ovarian tumor, a cervical tumor, a breast tumor, small cell lung tumor, a non-small cell lung tumor, a fallopian tube tumor, and a primary tumor of the peritoneum.  
     
     
         12 . The method of any one of the preceding claims, wherein the animal is a human.  
     
     
         13 . A pharmaceutical composition for modulating tumor growth or metastasis in an animal in need thereof, comprising carboplatin and a combretastatin A-4 phosphate prodrug salt in amounts effective therefore in a pharmaceutically acceptable carrier.  
     
     
         14 . The pharmaceutical composition of  claim 13 , wherein said carboplatin comprises a unit dosage form between AUC 4 and AUC 6.  
     
     
         15 . The pharmaceutical composition of  claim 13 , wherein said combretastatin A-4 phosphate prodrug salt comprises a unit dosage form of between 45 and 63 mg/kg.  
     
     
         16 . The pharmaceutical composition of  claim 13 , wherein said tumor is selected from the group consisting of a melanoma, an ovarian tumor, a cervical tumor, a breast tumor, small cell lung tumor, a non-small cell lung tumor, a fallopian tube tumor, and a primary tumor of the peritoneum.  
     
     
         17 . The pharmaceutical composition of  claim 13 , wherein said animal is a human.