Generic Name: Cabazitaxel
Brand Names: Various around the world
What is Cabazitaxel?
Cabazitaxel is an anticancer drug that belongs to the taxane category. Cabazitaxel side effects and uses will be discussed in detail below in the text. Some of the known commercial preparations that contain the active substance cabazitaxel are Jevtana, Cabazitax, and Cabazitec.
In 1986, scientists at Sanofi-Aventis, a pharmaceutical company, made the discovery of cabacizataxel. In the US, it was initially licenced for medical use in 2010. We shall examine data and information regarding Cabazitaxel in this article from scientific journals and medical research, including publications by Mita et al. in Clinical Cancer Research, Vrignaud et al. in Drug Design, Development and Therapy, and Galsky et al. in Nature Reviews Drug Discovery.
Therapeutic category
Cabazitaxel is a member of the taxanes class of antineoplastic medications. A class of natural substances discovered in plants belonging to the genus Taxus are the source of taxanes, a class of anticancer medications (fir). In this class, other well-known medications include docetaxel (Taxotere) and paclitaxel (Taxol).
Chemical structure and properties
The natural taxane 10-deacetylbaccatin III, which was extracted from the leaves of European Scots pine (Taxus baccata), is the semisynthetic derivative known as cabacizataxel. Its molecular weight is 835.93 g/mol and its formula is C45H57NO14. White to off-white crystalline powder, cabacitaxel is essentially insoluble in water.
Mechanism of action
Similar to other taxanes, capazitel acts by maintaining the stability of microtubules, which are important cytoskeleton elements necessary for fundamental cellular processes like cell division. It binds to tubulin and inhibits tubulin dimer disintegration while promoting tubulin dimer assembly into stable microtubules. This finally results in cell death (Vrignaud et al., “Cabazitaxel: A novel taxane for metastatic castration-resistant prostate cancer-current implications and future prospects”). It also causes microtubule stabilisation and cell cycle arrest in the G2/M phase.
Capazitel Use
Patients with metastatic castration-resistant prostate cancer who have already had treatment with a regimen comprising docetaxel may benefit from using cabotaxel in conjunction with prednisone or prednisolone. Additionally, it has being investigated as a treatment for non-small cell lung cancer and breast cancer, among other solid tumours (Abidi, “Cabazitaxel: more than a new taxane for metastatic castrate-resistant prostate cancer?”).
Warnings
Strong chemotherapy medication like capazitaxel should only be used under the guidance of a qualified oncologist. Throughout treatment, patients should be continuously observed and advised of any potential side effects. Cabazitaxel has been linked to severe hypersensitivity events, including anaphylaxis. Rash, itching, dyspnea, and facial or neck edoema are possible symptoms. In the event of serious reactions, treatment should be discontinued right away.
Precautions before taking Cabazitaxel
Patients should inform their doctor before beginning cabazitaxel treatment if they have a history of taxane allergies, liver or kidney issues, bone marrow diseases, or if they are already taking any other medications that may interfere with cabazitaxel. Cabazitaxel. Effective contraception should be used during and for three months following cabazitaxel treatment by both men and women who are or may become pregnant (Mita et al.).
Contraindications
Patients who have a history of cabazitaxel, other taxanes, or any of the drug’s excipients hypersensitivity should not take cabazitaxel. It should not be administered in conjunction with vaccines that include live or attenuated pathogens, or to patients who have a neutrophil count of less than 1,500 cells/mm3 or significant liver failure.
What to avoid
When using cabazitaxel, patients should refrain from ingesting grapefruit juice or grapefruit-based items since this could raise the drug’s blood levels and increase the chance of side effects. Additionally, they must refrain from receiving live or attenuated vaccinations for three months following treatment. The possibility of treatment-induced weariness and dizziness makes it necessary to minimise sun exposure and mentally demanding activities like driving.
Dosage and administration of Cabazitaxel
Every three weeks, a one-hour intravenous infusion of 25 mg/m2 of cabazitaxel is advised in conjunction with 10 mg of oral prednisone or prednisolone. At the treating physician’s discretion, patients may require intensive supportive care and antiemetic prophylaxis. Depending on the patient’s tolerance, dose modifications can be required (Vrignaud et al.).
Routes and methods of administration
Only intravenous infusion is used to provide cabotazitaxel. Cabazitaxel concentration needs to be diluted with either 0.9% sodium chloride solution or 5% glucose solution to the proper volume before being administered. Using an infusion set with an incorporated 0.22 micrometre filter, the prepared infusion should be given over the course of an hour. If cabazitaxel seeps outside the vein, it might cause severe tissue irritation, hence appropriate care should be taken to prevent extravasation.
What to do if I miss a dose of the drug Cabazitaxel?
A patient should call their doctor right away to get advice if they forget to take their cabazitaxel dosage. In general, the dose can be administered right away if it has been less than three hours after the planned dose. However, the dose is typically skipped and the subsequent dose is administered according to the regular schedule if more than three hours have elapsed. It is not appropriate to administer two doses to make up for a missing one. Patients should try their best to follow the recommended dosing schedule as missing doses can decrease the effectiveness of treatment.
Overdose
When cabazitaxel is overdosed, side effects such gastrointestinal toxicity, neurotoxicity, and bone marrow suppression may get worse. Cabazitaxel overdose does not currently have a particular antidote available. Supportive interventions include regular vital sign monitoring, hydration and electrolyte delivery, and, if necessary, the administration of antiemetics and granulocyte growth factors are also part of management. Patients who overdose should have the proper supportive care and be continuously watched for any indicators of toxicity (Mita et al.).
Cabazitaxel Side effects
The most common side effects of cabazitaxel include:
Thrombocytopenia, anaemia, and neutropenia
vomiting, nausea, and diarrhoea
Weakness and exhaustion
Peripheral neuropathy (pain, tingling, and numbness in the limbs)
Constipation
arthralgia and myalgia
Alopecia
Serious infections, haemorrhage, allergic responses, hypersensitivity reactions, and liver or kidney failure are examples of more severe side effects. If a patient experiences a high fever, chills, extreme weakness, bruising or bleeding, severe diarrhoea, or a severe rash, they should contact their doctor very away. There have also been reports of less common but potentially fatal adverse effects such posterior reversible encephalopathy syndrome and interstitial lung disease (Galsky et al.).
Cabazitaxel Interactions
Interactions between drugs
The primary cytochrome P450 enzyme responsible for the metabolism of capazitaxel is CYP3A4. Strong CYP3A4 inhibitors can raise blood levels of cabazitaxel and increase the risk of side effects. Examples of these inhibitors include grapefruit juice, ketoconazole, itraconazole, and clarithromycin. Inducers of CYP3A4 that can lower cabazitaxel levels and effectiveness include phenytoin, carbamazepine, and rifampicin. It is best to avoid using these medications concurrently with cabazitaxel (Vrignaud et al.).
Additionally, people taking anticoagulants like warfarin may be at higher risk of bleeding when using capazitaxel. When receiving cabazitaxel therapy, patients who are on anticoagulation may need more frequent monitoring and dose adjustments.
Drug-food interactions
When taking cabazitaxel, it is best to avoid consuming grapefruit juice or grapefruit-based items since they may raise the drug’s blood levels and increase the chance of side effects. Cabazitaxel is not known to interact with any other foods in a way that is clinically meaningful. Before making significant dietary changes while taking this medicine, however, patients should speak with their doctor (Abidi).
Additional important information
Special warnings for the elderly and children
Elderly individuals should use cabaretaxel with caution since they may be more vulnerable to the harmful effects of the medication, especially infections and neutropenia. Additionally, elderly patients may have diminished hepatic or renal function, necessitating a change in dosage. It is unknown if cabazitaxel is safe and effective for use in children and teenagers younger than 18 years old. Cabazitaxel is not indicated for metastatic castration-resistant prostate cancer in the paediatric population, according to Vignaud et al.
Development of resistance
Over time, cabazitaxel resistance may arise, resulting in decreased therapy efficacy. Increased expression of efflux pumps such P-glycoprotein, alterations in microtubules that lower cabazitaxel binding affinity, and modifications to signalling pathways that support tumour cell survival are a few possible mechanisms of resistance. Potential tactics to halt or prevent the emergence of resistance include combining cabazitaxel with other medications that target various resistance pathways (Galsky et al.).
Clinical studies of the drug Cabazitaxel
The phase III TROPIC pilot research assessed the safety and effectiveness of cabazitaxel in metastatic castration-resistant prostate cancer. 755 individuals who had previously received docetaxel treatment were randomly assigned to receive either mitoxantrone 12 mg/m² every three weeks together with prednisone or cabazitaxel 25 mg/m² every three weeks along with prednisone in this trial. Compared to mitoxantrone, capazitaxel showed a considerably higher overall survival rate (median 15.1 vs. 12.7 months, p < 0.0001). Additionally, according to Mita et al., cabaretaxel was linked to longer times until PSA advancement, increased rates of prostate-specific antigen (PSA) response, and enhanced pain response.
With good outcomes, cabazitaxel has also been investigated in combination with other medications, including prednisone, enzalutamide, and abiraterone. Cabazitaxel is being studied in other clinical studies for the treatment of different cancers, including lung and breast cancer, as well as prostate cancer at its earlier stages.
Comparative efficiency
Cabazitaxel has demonstrated enhanced effectiveness in indirect comparisons when compared to other treatments for metastatic castration-resistant prostate cancer that were administered after docetaxel failed. Direct head-to-head comparisons are limited, as response rates and durations differ throughout studies. Individualised treatment decisions should be made taking into account the patient’s preferences, history of treatment, and other considerations (Vrignaud et al.; Abidi).
Pharmacological characteristics
With a molecular weight of 835.93 g/mol and a formula of C45H57NO14, cabacitaxel is a semisynthetic taxane derivative. Compared to other taxanes, it has a lesser affinity for P-glycoprotein, which enables it to continue acting in drug-resistant cancer cells that produce this efflux pump.
Cabazitaxel has linear pharmacokinetics at dosages ranging from 10 to 30 mg/m² following intravenous injection. Its typical elimination half-life is 95 hours, and CYP3A4 is primarily responsible for its metabolism. Roughly 4% of cabazitaxel is eliminated by renal excretion, whereas 76% of a given dose is eliminated through faecal excretion (Vrignaud et al.). Cabazitaxel’s strong in vivo and in vitro anticancer impact further justifies its usage in treating prostate cancer and possibly other chemotherapy-resistant cancer types.
In brief
The anticancer medication cabacitaxel is a member of the taxanes class. It is used to treat patients with metastatic castration-resistant prostate cancer who have received docetaxel treatment in the past. By keeping microtubules stable, cabaretaxel inhibits the cell cycle and kills cancer cells. Every three weeks, it is administered intravenously, typically in conjunction with oral prednisone.
The most frequent adverse reactions of cabazitaxel are peripheral neuropathy, anaemia, diarrhoea, nausea, and exhaustion. Serious infections, hypersensitivity responses, and febrile neutropenia are examples of more severe side effects. CYP3A4 is the primary enzyme that metabolises capazitaxel, and it may interact with strong inducers or inhibitors of this enzyme.
Clinical trials like TROPIC have demonstrated that in patients with metastatic castration-resistant prostate cancer who have not responded to docetaxel therapy, cabazitaxel improves overall survival and response rates when compared with other medications. On the other hand, resistance can gradually build up. To maximise cabazitaxel’s efficacy, current research is exploring the drug’s use in combination with other medicines and in different forms of cancer.
ATTENTION: It is of vital importance to never take any medication without the supervision and guidance of a specialised doctor. Consult the package insert of each prescribed medicinal product, as each pharmaceutical company accurately describes the specific specifications for the product, which may undergo regular updates. Note that the trade names mentioned in this article correspond to well-known medicinal products that contain the active substances under analysis. However, there may be variations depending on the composition of each drug. This article focuses on the active substance analysis rather than the drug’s trade name. The reference to trade names is made exclusively for the convenience of readers, who should carefully study the instruction leaflet for each commercial preparation they use. It is necessary to have close cooperation with your attending physician and your pharmacist. The self-administration of any medication carries serious health risks and should be strictly avoided.
Bibliography
- Abidi, A. “Cabazitaxel: more than a new taxane for metastatic castrate-resistant prostate cancer?” Journal of Pharmacology and Pharmacotherapeutics, 2013. journals.sagepub
- Galsky, MD., A Dritselis, P Kirkpatrick, et al. “Cabazitaxel.” Nature Reviews Drug Discovery 9.9 (2010): 677-678. go.gale
- Mita, AC., R Figlin, MM Mita. “Cabazitaxel: more than a new taxane for metastatic castrate-resistant prostate cancer?” Clinical Cancer Research 18.24 (2012): 6574-6579. aacrjournals
- Vrignaud, P., D Semiond, V Benning, et al. “Preclinical profile of cabazitaxel.” Drug design, development and therapy 8 (2014): 1851. tandfonline
