Treatment of Epithelial Cysts by Intracystic Injection of Antineoplastic Particles

Abstract

Disclosed herein are methods for treating epithelial cysts including pancreatic cysts in a subject by intracystic injection of compositions comprising antineoplastic particles, including taxane particles such as paclitaxel particles and docetaxel particles.

1 . A method for treating an epithelial cyst, the method comprising injecting a composition comprising an effective amount of antineoplastic particles directly into the cyst, thereby treating the epithelial cyst, wherein the particles have a mean particle size (number) of from 0.1 microns to 5 microns. 
     
     
         2 . The method of  claim 1 , wherein the composition further comprises a liquid carrier, and wherein the composition comprises a suspension of the antineoplastic particles dispersed in the carrier. 
     
     
         3 . The method of  claim 2 , wherein the carrier is an aqueous carrier. 
     
     
         4 . The method of  claim 3 , wherein the aqueous carrier comprises 0.9% saline solution. 
     
     
         5 . The method of  claim 3 , wherein the aqueous carrier comprises a surfactant. 
     
     
         6 . The method of  claim 5 , wherein the surfactant is a polysorbate. 
     
     
         7 . The method of  claim 6 , wherein the polysorbate is polysorbate 80, and wherein the polysorbate 80 is present in the aqueous carrier at a concentration of between about 0.01% v/v and about 1% v/v. 
     
     
         8 . The method of  claim 3 , wherein the composition further comprises a diluent, wherein the carrier and the diluent form a mixture, and wherein the composition is a suspension of the antineoplastic particles dispersed in the carrier/diluent mixture. 
     
     
         9 . The method of  claim 8 , wherein the diluent is a 0.9% saline solution. 
     
     
         10 . The method of  claim 1 , wherein the antineoplastic particles are taxane particles. 
     
     
         11 . The method of  claim 10 , wherein the taxane particles comprise at least 95% of the taxane, wherein the taxane particles have a mean particle size (number) of from 0.1 microns to 1.5 microns, and wherein the composition and taxane particles exclude albumin. 
     
     
         12 . The method of  claim 10 , wherein the concentration of taxane particles in the composition is between about 6 mg/mL and about 15 mg/mL. 
     
     
         13 . The method of  claim 10 , wherein the taxane particles are paclitaxel particles. 
     
     
         14 . The method of  claim 13 , wherein the paclitaxel particles have a specific surface area (SSA) of at least 18 m 2 /g. 
     
     
         15 . The method of  claim 13 , wherein the paclitaxel particles have a bulk density (not-tapped) of 0.05 g/cm 3  to 0.15 g/cm 3 . 
     
     
         16 . The method of  claim 10 , wherein the taxane particles are docetaxel particles. 
     
     
         17 . The method of  claim 16 , wherein the docetaxel particles have a specific surface area (SSA) of at least 18 m 2 /g. 
     
     
         18 . The method of  claim 16 , wherein the docetaxel particles have a bulk density (not-tapped) of 0.05 g/cm 3  to 0.15 g/cm 3 . 
     
     
         19 . The method of  claim 1 , wherein the cyst fluid is withdrawn from the cyst prior to injecting the composition. 
     
     
         20 . The method of  claim 19 , wherein the volume of the composition injected into the cyst is equal to the volume of cyst fluid removed from the cyst. 
     
     
         21 . The method of  claim 1 , wherein the epithelial cyst is a pancreatic cyst. 
     
     
         22 . The method of  claim 21 , wherein the pancreatic cyst is a mucinous pancreatic cyst. 
     
     
         23 . The method of  claim 1 , wherein the injection of the composition is conducted by endoscopic ultrasound-guided fine needle injection (EUS-FNI). 
     
     
         24 . The method of  claim 1 , wherein the epithelial cyst is reduced in volume/size, has reduced growth rate, is eliminated, or is ablated after injection of the composition, and/or wherein the pain associated with the cyst is reduced. 
     
     
         25 . The method of  claim 1 , wherein the epithelial cyst is benign. 
     
     
         26 . A kit comprising:
 (a) a first vial comprising taxane particles;   (b) a second vial comprising a pharmaceutically acceptable aqueous carrier and a surfactant; and   (c) instructions for reconstituting the taxane particles into a suspension useful for intracystic injection by: combining the contents of the first vial and the second vial to form the suspension and optionally diluting the suspension with a diluent.   
     
     
         27 .- 36 . (canceled) 
     
     
         37 . A method of administering a composition comprising antineoplastic particles to an epithelial cyst of a subject, the method comprising injecting the composition into the cyst using endoscopic ultrasound guided-fine needle injection, wherein the antineoplastic particles have a mean particle size (number) of from 0.1 microns to 5 microns, and wherein the antineoplastic particles are crystalline particles. 
     
     
         38 . The method of  claim 37 , wherein the antineoplastic particles have a mean particle size (number) of from 0.3 microns to 5 microns. 
     
     
         39 . The method of  claim 37 , wherein the antineoplastic particles are taxane particles.