What is Cabazitaxel?
Cabazitaxel, a second-line drug for prostate cancer treatment, is a next-generation synthetic paclitaxel antitumor agent that was launched in the United States in 2010 and in Europe in 2011.
The use of cabazitaxel in the second-line treatment of castration-resistant prostate cancer (CRPC) is a landmark because it extends survival in patients with CRPC who have developed resistance to docetaxel.
A phase III clinical registry study led by the Tropic team involving 146 medical centers in 26 countries enrolled 755 patients with destructive-resistant prostate cancer who progressed during and after treatment with docetaxel-based regimens, divided into treatment (cabazitaxel + prednisone) and control groups (mitoxantrone + prednisone).
The results found that the treatment group compared with the control group:
- The risk of patient death was reduced by 28%;
- 25% lower risk of disease progression;
- PSA efficiency was higher (39.2% versus 17.8%).
It was based on the results of this study that the FDA approved cabazitaxel for the treatment of patients with debulking-resistant prostate cancer.
The most authoritative international guidelines for the treatment of prostate cancer, the European Association of Urology (EAU) guidelines and the US NCCN (national comprehensive cancer network) guidelines both recommend cabazitaxel as second-line treatment for debulking-resistant prostate cancer.
What is the antitumor mechanism of cabazitaxel?
Cabataxel is a microtubule inhibitor that promotes the assembly of microtubules by binding to microtubule proteins, while preventing the disassembly of these already assembled microtubules, which leads to microtubule stabilization and thus inhibits mitotic and interphase cellular function.
Studies have shown that cabazitaxel has activity against docetaxel-sensitive tumors and anti-tumor activity against tumor models that include docetaxel-insensitive chemotherapy.
In addition, by altering cell cycle regulators, such as cell cycle protein A and cell cycle protein B1, cabazitaxel induces cell cycle arrest, inhibits proliferation, and causes apoptosis, while the expression of transcriptional regulators and epidermal growth factor receptors in tumor cells is also inhibited.
What are the adverse effects associated with cabazitaxel treatment?
The most common adverse reaction to cabazitaxel is anemia. More serious adverse reactions include neutropenia, allergic reactions, gastrointestinal symptoms, and renal failure.
Blood counts need to be monitored frequently during cabazitaxel treatment to determine if granulocyte-colony stimulating factor (G-CSF) needs to be initiated and the dose adjusted to prevent serious consequences of neutropenia.
Carbataxel also has the potential to cause severe allergic reactions, and corticosteroids and H2 receptor antagonists may be given prior to dosing. If there are signs of an allergic reaction during administration, the infusion should be stopped immediately.
If severe gastrointestinal symptoms occur, such as nausea, vomiting, or diarrhea, an antiemetic may be used or the dose of the drug may be adjusted; the cause should first be identified in patients who develop renal failure.
Elderly patients ≥65 years of age are more likely to have disease progression or certain serious adverse reactions, including neutropenia and febrile neutropenia leading to fatal consequences, and need to be monitored closely; impaired hepatic function may increase cabazitaxel concentrations and therefore should not receive cabazitaxel therapy.
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