Methods of treatment of a bcl-2 disorder using bcl-2 antisense oligomers

Abstract

The present invention is directed to the use of bcl-2 antisense oligomers to treat and prevent bcl-2 related disorders. These disorders include cancers, tumors, carcinomas and cell-proliferative related disorders. In one embodiment of the invention, a bcl-2 antisense oligomer is administered at high doses. The present invention is also directed to a method of preventing or treating a bcl-2 related disorder, in particular cancer, comprising administering a bcl-2 antisense oligomer for short periods of time. The present invention is further drawn to the use of bcl-2 antisense oligomers to increase the sensitivity of a subject to cancer therapeutics. The present invention also relates to pharmaceutical compositions comprising one or more bcl-2 antisense oligomers, which may comprise one or more cancer therapeutic agents.

1 . A method for treating cancer in a human comprising administering to a human, in which such treatment is desired, a bcl-2 antisense oligonucleotide at a dose of 8-9 mg/kg/day, 9-10 mg/kg/day or 10-50 mg/kg/day for 1-10 days, and further comprising administering one or more cancer therapeutics. 
   
   
       2 . The method of  claim 1 , wherein a daily dose is administered by injection. 
   
   
       3 . The method of  claim 2 , wherein the daily dose is administered in a single bolus administration. 
   
   
       4 . The method of  claim 2 , wherein the daily dose is divided into several partial administrations. 
   
   
       5 . The method of  claim 2 , wherein the daily dose is administered in multiple subcutaneous injections. 
   
   
       6 . The method of  claim 1 , wherein a daily dose is administered by intravenous infusion. 
   
   
       7 . The method of  claim 1  further comprising a treatment cycle consisting of 2-13 days. 
   
   
       8 . The method of  claim 7  further comprising a treatment cycle consisting of 10-13 days, 7-9 days or 5-6 days. 
   
   
       9 . The method of  claim 1 , wherein the dose is administered prior to, subsequently to or concurrently with the cancer therapeutic. 
   
   
       10 . The method of  claim 1 , wherein the dose is administered for 2 to 7 days or 3 to 4 days. 
   
   
       11 . A composition for bolus administration to a human comprising 8-9 mg/kg, 9-10 mg/kg or 10-50 mg/kg of a bcl-2 antisense oligomer and a pharmaceutically acceptable carrier in a single-dose vial. 
   
   
       12 . The composition of  claim 11  which is formulated for injection. 
   
   
       13 . The composition of  claim 11  which is formulated for intravenous administration. 
   
   
       14 . The composition of  claim 11  wherein the composition comprises 10-50 mg/kg/day of the bcl-2 antisense oligomer.