Compositions, Devices and Methods of Use Thereof for the Treatment of Cancers

Abstract

The use of GLP-1 receptor agonists, such as glucagon-like peptide-1 (GLP-1) or exenatide, for the treatment of cancer is described. The GLP-1 receptor agonists are typically delivered using an implanted osmotic delivery device that provides for continuous delivery of the GLP-1 receptor agonist for at least one month. Additional beneficial agents, such as anticancer agents, can also be administered.

1 . A method of treating cancer in a subject in need of such treatment, comprising administering a GLP-1 receptor agonist to the subject. 
     
     
         2 . The method of  claim 1 , wherein the GLP-1 receptor agonist is a peptide, polypeptide or protein. 
     
     
         3 . The method of  claim 2 , wherein the GLP-1 receptor agonist is a glucagon-like peptide-1 (GLP-1), a derivative of GLP-1, or an analog of GLP-1. 
     
     
         4 . The method of  claim 3 , wherein the GLP-1 receptor agonist is GLP(7-36)amide comprising the sequence of SEQ ID NO:1. 
     
     
         5 . The method of  claim 3 , wherein the GLP-1 receptor agonist is selected from the group consisting of liraglutide, albiglutide, semaglutide and taspoglutide. 
     
     
         6 . The method of  claim 2 , wherein the GLP-1 receptor agonist is exenatide, a derivative of exenatide, or an analog of exenatide. 
     
     
         7 . The method of  claim 6 , wherein the GLP-1 receptor agonist is synthetic exenatide peptide comprising the sequence of SEQ ID NO:2. 
     
     
         8 . The method of  claim 6 , wherein the GLP-1 receptor agonist is lixisenatide. 
     
     
         9 . The method of  claim 1 , wherein the GLP-1 receptor agonist is provided in a suspension formulation comprising:
 (a) a particle formulation comprising the GLP-1 receptor agonist; and   (b) a vehicle formulation,   wherein the particle formulation is dispersed in the vehicle.   
     
     
         10 . The method of  claim 9 , wherein (a) the particle formulation additionally comprises a disaccharide, methionine and a buffer and (b) the vehicle formulation is a non-aqueous, single-phase suspension vehicle comprising one or more pyrrolidone polymers and one or more solvents selected from the group consisting of lauryl lactate, lauryl alcohol, benzyl benzoate, and mixtures thereof;
 wherein the suspension vehicle exhibits viscous fluid characteristics, and the particle formulation is dispersed in the vehicle.   
     
     
         11 . The method of  claim 10 , wherein the buffer is selected from the group consisting of citrate, histidine, succinate, and mixtures thereof. 
     
     
         12 . The method of  claim 10 , wherein the disaccharide is selected from the group consisting of lactose, sucrose, trehalose, cellobiose, and mixtures thereof. 
     
     
         13 . The method of  claim 10 , wherein the particle formulation is a spray dried preparation of particles. 
     
     
         14 . The method of  claim 10 , wherein the vehicle consists essentially of polyvinylpyrrolidone and benzyl benzoate. 
     
     
         15 . The method of  claim 14 , wherein the vehicle is about 50% solvent and about 50% polymer. 
     
     
         16 . The method of  claim 10 , wherein the suspension formulation has an overall moisture content of less than or equal to about 10 wt %. 
     
     
         17 . The method of  claim 9 , wherein the CLP-1 receptor agonist is delivered using an implantable osmotic delivery device. 
     
     
         18 . The method of  claim 1 , wherein the GLP-1 receptor agonist is provided in an injectable formulation. 
     
     
         19 . The method of  claim 1 , wherein one or more beneficial agent in addition to the GLP-1 receptor agonist is delivered to the subject, and the beneficial agent is an anticancer agent, a chemotherapeutic agent, or an antidiabetic agent. 
     
     
         20 . The method of  claim 19 , wherein the additional beneficial agent is delivered using an implantable osmotic delivery device.