NOVEL ANTITUMORAL USE OF CABAZITAXEL
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.
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.