Methods for treatment of bladder cancer with gemcitabine

Abstract

Drug delivery devices and methods are provided for administering gemcitabine to a patient in need of treatment of bladder cancer by intravesically administering gemcitabine into the bladder of the patient to achieve a sustained concentration of the gemcitabine in urine in the bladder sufficient to produce a therapeutically effective concentration of the gemcitabine in the tissues of the bladder. In embodiments, the local administration into the patient's bladder is at a mean average amount of from 1 mg/day to about 300 mg/day of the gemcitabine (FBE).

We claim: 
     
         1 . A method for treating non-muscle invasive bladder cancer (NMIBC) in a human patient, comprising:
 deploying into the patient's bladder an intravesical drug delivery device which comprises gemcitabine; and   releasing the gemcitabine from the intravesical drug delivery device into the patient's bladder to produce a therapeutic concentration of the gemcitabine in bladder tissues effective to treat NMIBC in the patient,   wherein the gemcitabine is released continuously into the patient's bladder, at a mean average amount of from 10 mg/day to 50 mg/day of the gemcitabine free base equivalent (FBE) over a treatment period of from 7 day to 21 days, and   wherein the intravesical device releases the gemcitabine in a manner that produces gemcitabine urine concentrations in the bladder that are well tolerated by the urothelium.   
     
     
         2 . The method of  claim 1 , wherein the intravesical drug delivery device comprises a housing which contains and controls release of the gemcitabine. 
     
     
         3 . The method of  claim 2 , wherein the housing comprises a release orifice in communication with a drug reservoir in which the gemcitabine is contained along with an osmotic agent. 
     
     
         4 . A method for treating non-muscle invasive bladder cancer (NMIBC) in a human patient, comprising:
 deploying into the patient's bladder an intravesical drug delivery device which comprises gemcitabine; and   releasing the gemcitabine from the intravesical drug delivery device into the patient's bladder to produce a therapeutic concentration of the gemcitabine in bladder tissues effective to treat NMIBC in the patient,   wherein the gemcitabine is released continuously into the patient's bladder, at a mean average amount of from 10 mg/day to 50 mg/day of the gemcitabine (FBE) over a treatment period of 14 days to 21 days, and   wherein the intravesical device releases the gemcitabine in a manner that produces gemcitabine urine concentrations in the bladder that are well tolerated by the urothelium.   
     
     
         5 . The method of  claim 4 , wherein the intravesical drug delivery device comprises a housing which contains and controls release of the gemcitabine. 
     
     
         6 . The method of  claim 5 , wherein the housing comprises a laser-drilled release orifice in communication with a drug reservoir in which the gemcitabine is contained along with an osmotic agent and a viscosity enhancing agent. 
     
     
         7 . A method for treating non-muscle invasive bladder cancer (NMIBC) in a human patient, comprising:
 deploying into the patient's bladder an intravesical drug delivery device which comprises gemcitabine; and   releasing the gemcitabine from the intravesical drug delivery device into the patient's bladder to produce a therapeutic concentration of the gemcitabine in bladder tissues effective to treat NMIBC in the patient,   wherein the gemcitabine is released continuously into the patient's bladder, at a mean average amount of about 10 mg/day of the gemcitabine (FBE) over a treatment period of from 7 days to 21 days, and   wherein the intravesical device releases the gemcitabine in a manner that produces gemcitabine urine concentrations in the bladder that are well tolerated by the urothelium.   
     
     
         8 . The method of  claim 9 , wherein the intravesical drug delivery device comprises a housing which contains and controls release of the gemcitabine. 
     
     
         9 . The method of  claim 8 , wherein the housing comprises a release orifice in communication with a drug reservoir in which the gemcitabine is contained along with an osmotic agent. 
     
     
         10 . The method of  claim 8 , wherein the housing comprises a laser-drilled release orifice in communication with a drug reservoir in which the gemcitabine is contained along with an osmotic agent and a viscosity enhancing agent. 
     
     
         11 . A method for treating non-muscle invasive bladder cancer (NMIBC) in a human patient, comprising:
 deploying into the patient's bladder an intravesical drug delivery device which comprises gemcitabine HCl; and   releasing the gemcitabine from the intravesical drug delivery device into the patient's bladder to produce a therapeutic concentration of the gemcitabine in bladder tissues effective to treat NMIBC in the patient,   wherein the gemcitabine is released continuously into the patient's bladder, at a mean average amount of from 10 mg/day to 50 mg/day of the gemcitabine (FBE) over a treatment period of 7 days to 21 days, and   wherein the intravesical device releases the gemcitabine by osmotic pressure in a manner that produces gemcitabine urine concentrations in the bladder that are well tolerated by the urothelium.   
     
     
         12 . The method of  claim 11 , wherein the intravesical drug delivery device comprises a housing which contains and controls release of the gemcitabine through a laser-drilled release orifice in communication with a drug reservoir in which the gemcitabine is contained. 
     
     
         13 . The method of  claim 12 , wherein the drug reservoir further comprises an osmotic agent. 
     
     
         14 . The method of  claim 12 , wherein the drug reservoir further comprises an osmotic agent and a viscosity enhancing agent. 
     
     
         15 . The method of  claim 12 , wherein the laser-drilled release orifice is a 150-micron orifice.