Cabazitaxel

835.93238

835.93

1308068-626-2

51F690397J

761432

DTXSID40171389

C66937

L01CD|L01CD04|L - Antineoplastic and immunomodulating agents

29329990

202

2.7

Solid

1.31

870.7±65.0 °C(Predicted)

480.4±34.3 °C

1.592

24/25

P201, P202, P260, P261, P263, P264, P270, P271, P272, P280, P281, P301+P312, P302+P352, P304+P340, P305+P351+P338, P308+P313, P310, P312, P314, P321, P322, P330, P332+P313, P333+P313, P361, P362, P363, P403+P233, P405, P501

H302

|Danger|H302 (80%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P260, P261, P263, P264, P270, P271, P272, P273, P280, P281, P301+P312, P302+P352, P304+P340, P305+P351+P338, P308+P313, P310, P312, P314, P321, P322, P330, P332+P313, P333+P313, P361, P362, P363, P391, P403+P233, P405, and P501|Aggregated GHS information provided by 5 companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Cabazitaxel may cause serious side effects including neutropenia, hypersensitivity reactions, gastrointestinal symptoms, and renal failure. Anticipated complications of overdose include exacerbation of adverse reactions such as bone marrow suppression and gastrointestinal disorders. Cabazitaxel penetrates the blood-brain barrier. LD50, rat = 500 mg/kg

In the clinical trials and open label studies of cabazitaxel in metastatic prostate cancer, serum enzyme elevations were usually not mentioned and hepatic adverse events did not appear in lists of serious adverse events. The product label for cabazitaxel states that elevations of serum ALT and AST above 5 times ULN occur in less than 1% of treated patients. Cabazitaxel has not been linked convincingly to instances of idiosyncratic, clinically apparent liver injury with jaundice.

Cabazitaxel is mainly bound to human serum albumin (82%) and lipoproteins (88% for HDL, 70% for LDL, and 56% for VLDL).

For treatment of patients with hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing treatment regimen.|FDA Label|Jevtana in combination with prednisone or prednisolone is indicated for the treatment of patients with hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen.|Treatment of prostate cancer|Treatment of patients with hormone refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen.|Drug: Cabazitaxel

Cabazitaxel is a taxane and antineoplastic agent which is currently used in the therapy of castration-resistant metastatic prostate cancer after failure of docetaxel. Therapy with cabazitaxel has been associated with a low rate of serum enzyme elevations, but has not been linked to cases of clinically apparent acute liver injury, although it can cause severe hypersensitivity infusion reactions which in some instances can be associated with acute liver injury.

Antineoplastic Agents

Cabaitaxel has anti-tumour properties and is effective against docetaxel-sensitive and -insensitive tumours.

After an intravenous dose of cabazitaxel 25 mg/m2 every three weeks to a population of 170 patients with solid tumors, the mean Cmax in patients with metastatic prostate cancer was 226 ng/mL (CV 107%) and was reached at the end of the one-hour infusion (Tmax). The mean AUC in patients with metastatic prostate cancer was 991 ng.h/mL (CV 34%). Administration with prednisone or prednisolone do not effect the pharmacokinetic profile of cabazitaxel.|After a one-hour intravenous infusion [14C]-cabazitaxel 25 mg/m2, approximately 80% of the administered dose was eliminated within 2 weeks. Cabazitaxel is mainly excreted in the feces as numerous metabolites (76% of the dose); while renal excretion of cabazitaxel and metabolites account for 3.7% of the dose (2.3% as unchanged drug in urine).|The volume of distribution (Vss) was 4,864 L (2,643 L/m2 for a patient with a median BSA of 1.84 m2) at steady state. Compared to other taxanes, penetrates the CNS to a greater extent.|Cabazitaxel has a plasma clearance of 48.5 L/h (CV 39%; 26.4 L/h/m2 for a patient with a median BSA of 1.84 m2) in patients with metastatic prostate cancer.

Cabazitaxel is extensively metabolized in the liver (>95%), mainly by the CYP3A4/5 isoenzyme (80% to 90%), and to a lesser extent by CYP2C8 which results in 20 different metabolites. Two of these metabolites are active demethylated derivatives of cabaxitaxel and referred to as RPR112698 and RPR123142 respectively. Docetaxel is another metabolite of cabazitaxel. Cabazitaxel is the main circulating moiety in human plasma.

Following a one-hour intravenous infusion, plasma concentrations of cabazitaxel can be described by a three-compartment pharmacokinetic model with α-, β-, and γ- half-lives of 4 minutes, 2 hours, and 95 hours, respectively.

Cabazitaxel is a microtubule inhibitor. Cabazitaxel binds to tubulin and promotes its assembly into microtubules while simultaneously inhibiting disassembly. This leads to the stabilization of microtubules, which results in the interference of mitotic and interphase cellular functions. The cell is then unable to progress further into the cell cycle, being stalled at metaphase, thus triggering apoptosis of the cancer cell.

cabazitaxel

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