Novel antitumoral use of cabazitaxel

Abstract

The invention relates to a compound of formula: which may be in base form or in the form of a hydrate or a solvate, in combination with prednisone or prednisolone, for its use as a medicament in the treatment of prostate cancer, particularly metastatic prostate cancer, especially for patients who are not catered for by a taxane-based treatment.

What is claimed is: 
     
         1 . A method for treating prostate cancer in a patient in need thereof comprising administering to said patient a compound of formula 
       
         
           
           
               
               
           
         
       
       which may be in base form or in the form of a hydrate or a solvate, in combination with prednisone or prednisolone. 
     
     
         2 . The method according to  claim 1 , where the treated patients are not catered for by a taxane-based treatment. 
     
     
         3 . The method according to  claim 1 , where the patients treated have been previously treated with a docetaxel-based regimen. 
     
     
         4 . The method according to  claim 1 , where the prostate cancer is an advanced metastatic disease. 
     
     
         5 . The method according to  claim 1 , where the prostate cancer is a castration resistant prostate cancer or hormone-refractory prostate cancer. 
     
     
         6 . The method according to  claim 1 , where the compound is in the form of an acetone solvate. 
     
     
         7 . The method according to  claim 6 , in which the acetone solvate contains between 5% and 8% by weight of acetone. 
     
     
         8 . The method according to  claim 1 , where the compound is administered at a dose of between 15 and 25 mg/m 2 , the prednisone or prednisolone being administered at a dose of 10 mg/day. 
     
     
         9 . The method according to  claim 8 , where the compound is administered at a dose of 25 mg/m 2 . 
     
     
         10 . The method according to  claim 1 , comprising repeating the administration of such compound as a new cycle every 3 weeks. 
     
     
         11 . The method according to  claim 10 , wherein the median number of cycles is 6. 
     
     
         12 . The method according to  claim 1 , where the compound is administered in combination with prednisone for the treatment of patients with castration resistant metastatic prostate cancer or hormone-refractory prostate cancer and who have been previously treated with docetaxel based regimen. 
     
     
         13 . The method according to  claim 12 , where the compound is cabazitaxel. 
     
     
         14 . The method according to  claim 1 , wherein said compound is administered in an amount to provide an AUC of about 991 ng·h/mL (CV 34%). 
     
     
         15 . The method according to  claim 1 , wherein said compound is administered in an amount to provide an C max  of about 226 ng·h/mL (CV 107%). 
     
     
         16 . The method according to  claim 1  wherein said compound is administered in an amount to provide a plasma clearance of 48.5 L/h (CV 39%). 
     
     
         17 . The method according to  claim 1 , further comprising monitoring blood counts and measuring neutrophil levels in the patient. 
     
     
         18 . The method according to  claim 17 , wherein said monitoring comprises taking a blood sample from the patient. 
     
     
         19 . The method according to  claim 18 , further comprising discontinuing cabazitaxel treatment in a patient with a neutrophil count of ≦1,500 cells/mm 3 . 
     
     
         20 . A pharmaceutical composition comprising a compound as defined in  claim 1 . 
     
     
         21 . A method of reducing the risk of neutropenia complications in a patient with prostate cancer being treated with a compound as defined in  claim 1 , comprising monitoring blood counts in the patient at regular intervals during treatment of the patient; reducing the dose of the compound if the patient experiences febrile neutropenia or prolonged neutropenia; discontinuing the treatment if the patient's neutrophil count is ≦1,500 cells/mm 3 ; and optionally restarting the treatment when the patient's neutrophil counts recover to a level ≧1,500 cells/mm 3 . 
     
     
         22 . The method according to  claim 21 , further comprising administering G-CSF to a patient prior to the compound administration, wherein said patient is considered to be at increased risk for neutropenia complications. 
     
     
         23 . A method of reducing the risk of a severe hypersensitivity reaction in a patient with prostate cancer being treated with a compound as defined in  claim 1  comprising administering to the patient a medication to prevent hypersensitivity prior to the administration of cabazitaxel. 
     
     
         24 . A method of increasing the survival of a patient with hormone refractory metastatic prostate cancer, comprising administering a clinically proven effective amount of a compound as defined in  claim 1  to the patient in combination with prednisone or prednisolone. 
     
     
         25 . An article of manufacture comprising:
 a) a packaging material;   b) cabazitaxel, and   c) a label or package insert contained within the packaging material indicating that cabazitaxel should not be given to patients with neutrophil counts of ≦1,500 cells/mm 3 .   
     
     
         26 . An article of manufacture comprising:
 a) a packaging material;   b) cabazitaxel, and   c) a label or package insert contained within the packaging material indicating that severe hypersensitivity reactions can occur.   
     
     
         27 . A package comprising cabazitaxel and a label, said label comprising one or more messages that:
 a) the efficacy and safety of cabazitaxel in combination with prednisone were evaluated in patients with hormone refractory metastatic prostate cancer previously treated with a docetaxel containing regimen;   b) a total of 755 patients were randomized to receive either cabazitaxel 25 mg/m 3  every 3 weeks for a maximum of 10 cycles with prednisone mg orally daily, or to receive mitoxantrone 12 mg/m 2  intravenously every 3 weeks for a maximum of 10 cycles with prednisone 10 mg orally daily; or   c) the median number of cycles was 6 in the cabazitaxel group and 4 in the mitoxantrone group.   
     
     
         28 . A package comprising cabazitaxel and a label, said label comprising one or more messages that:
 a) neutropenic deaths have been reported;   b) frequent blood counts should be obtained to monitor for neutropenia; or   c) cabazitaxel should not be given if neutrophil counts are ≦1,500 cells/mm 3 .   
     
     
         29 . A package comprising cabazitaxel and a label said label comprising a printed statement which informs a reader that the mean C max  of cabazitaxel in patients with metastatic prostate cancer was 226 ng/mL (CV 107%). 
     
     
         30 . A package comprising cabazitaxel and a label, said label comprising a printed statement which informs a reader that the mean AUC of cabazitaxel in patients with metastatic prostate cancer was 991 ng·h/mL (CV 34%). 
     
     
         31 . A package comprising cabazitaxel and a label, said label comprising a printed statement which informs a reader that cabazitaxel has a plasma clearance of 48.5 L/h (CV 39%). 
     
     
         32 . A method of promoting the use of cabazitaxel, the method comprising the step of conveying to a recipient at least one message selected from:
 a) neutropenic deaths have been reported;   b) frequent blood counts should be obtained to monitor for neutropenia;   c) cabazitaxel should not be given if neutrophil counts are ≦1,500 cells/mm 3 ;   d) severe hypersensitivity can occur;   e) severe hypersensitivity can occur and may include generalized rash/erythema, hypotension and brochospasm;   f) discontinue cabazitaxel immediately if severe reactions occur;   g) discontinue cabazitaxel immediately if severe reactions occur and administer appropriate therapy; or   h) cabazitaxel is contraindicated in patients with a history of severe hypersensitivity reactions to cabazitaxel or drugs formulated with polysorbate 80.   
     
     
         33 . A method of providing cabazitaxel, wherein said cabazitaxel is provided along with information indicating that:
 a) neutropenic deaths have been reported;   b) frequent blood counts should be obtained to monitor for neutropenia;   c) cabazitaxel should not be given if neutrophil counts are ≦1,500 cells/mm 3 ;   d) severe hypersensitivity can occur;   e) severe hypersensitivity can occur and may include generalized rash/erythema, hypotension and brochospasm;   f) discontinue cabazitaxel immediately if severe reactions occur;   g) discontinue cabazitaxel immediately if severe reactions occur and administer appropriate therapy; or   h) cabazitaxel is contraindicated in patients with a history of severe hypersensitivity reactions to cabazitaxel or drugs formulated with polysorbate 80.