Cabazitaxel
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Cabazitaxel: From Prostate Cancer (Taxane Chemotherapy) to Female Breast Carcinoma
One-Sentence Summary
Cabazitaxel is a taxane chemotherapy drug, known in the literature for treating metastatic castration-resistant prostate cancer after docetaxel. The TxGNN model predicts it may be effective for female breast carcinoma. Currently there are no registered clinical trials in the data compiled for this report, but 20 publications exist, mostly preclinical or review articles, plus two phase I/II and phase II clinical studies.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the Singapore licence record (literature describes metastatic castration-resistant prostate cancer after docetaxel) |
| Predicted New Indication | Female breast carcinoma |
| TxGNN Prediction Score | 99.92% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the compiled data. Based on known information, cabazitaxel is a taxane that stabilises microtubules and disrupts mitotic spindle dynamics, the same class mechanism as docetaxel and paclitaxel, both established in breast cancer.
Cabazitaxel is also a weak P-glycoprotein substrate. It may therefore retain activity in taxane-resistant tumours, and preclinical work shows it is less cross-resistant than paclitaxel and docetaxel in some resistant cell models.
The supplied literature is largely indirect: nanoparticle and lipid formulation studies in breast cancer cell lines and xenografts, resistance-mechanism studies, and pharmacology reviews. Only a few clinical studies are included (see below).
Clinical Trial Evidence
Currently no related clinical trials are registered in the data compiled for this report. Two published clinical studies appear in the literature table below.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 28768217 | 2017 | Randomised phase II | Eur J Cancer | GENEVIEVE: neoadjuvant cabazitaxel vs weekly paclitaxel in operable triple-negative or luminal B/HER2-negative breast cancer, comparing pathological complete response |
| 38663168 | 2024 | Randomised phase II (long-term follow-up) | ESMO Open | Long-term outcomes of GENEVIEVE, assessing whether the earlier pCR differences carried into long-term outcome |
| 21339064 | 2011 | Phase I/II | Eur J Cancer | Cabazitaxel plus capecitabine in metastatic breast cancer after anthracycline and taxane; assessed maximum tolerated dose, safety, pharmacokinetics and activity |
| 33753567 | 2021 | Preclinical | J Immunother Cancer | Cabazitaxel's effect on macrophages improves CD47-targeted immunotherapy in triple-negative breast cancer |
| 25416788 | 2015 | Preclinical/Review | Mol Cancer Ther | Resistance mechanisms; cabazitaxel less cross-resistant than paclitaxel and docetaxel in MCF-7-derived models |
| 30529259 | 2019 | Preclinical | J Control Release | Nanoparticle-encapsulated cabazitaxel gave complete remission of 6 of 8 tumours in a patient-derived breast cancer xenograft |
| 38562610 | 2024 | Preclinical | Int J Nanomedicine | Efficacy of cabazitaxel-loaded PACA nanoparticle variants, following earlier triple-negative breast cancer xenograft results |
| 28504249 | 2017 | Preclinical | Acta Pharmacol Sin | Cabazitaxel-loaded polymeric micelles evaluated against breast cancer metastasis |
| 21076710 | 2010 | Review | Drugs Today | Favourable pharmacokinetic and safety profile; reduced P-gp-mediated resistance; neutropenia and neuropathy most common toxicities |
| 33247980 | 2021 | Review | Br J Clin Pharmacol | Overview of taxane pharmacology and therapeutic drug monitoring-based dose adjustment |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN14043P | Jevtana® Concentrate and Solvent for Solution for Infusion 60mg/1.5ml | Infusion, solution concentrate | Not stated in the licence record |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (taxane, microtubule inhibitor) |
| Myelosuppression Risk | High (neutropenia is a leading toxicity; the knowledge graph also links the drug to leukopenia, thrombocytopenia, agranulocytosis and anaemia) |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | CBC with differential, liver function (including bilirubin), renal function |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Safety Considerations
- Knowledge-graph contraindication signals (from a model knowledge graph, not label text): kidney disease, liver disease, gallbladder disease, thrombocytopenia, neutropenia, agranulocytosis, anaemia, macrocytic anaemia, hyperbilirubinaemia, hereditary hyperbilirubinaemia, Gilbert syndrome, leukopenia, pyoureter.
- Drug Interactions (100 interactions found; selected examples):
- Major: deferiprone, samarium (153Sm) lexidronam (both likely additive myelosuppression concerns)
- Moderate: aprepitant, clarithromycin, clotrimazole, miconazole, metronidazole, tinidazole, rosuvastatin, simvastatin, cobicistat, deferasirox, ticagrelor, chloroquine, disulfiram, and others
Please also refer to the package insert for official warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The breast cancer prediction is mechanistically plausible because taxanes are already established there, and a randomised phase II study (GENEVIEVE) exists. However, no registered trials are in the compiled data, the evidence is mostly preclinical or indirect, and the local licence record contains no approved indication or label safety text. Other predicted indications (sickle cell syndromes, HIV, hyperthyroidism, neuroblastoma, rheumatoid arthritis) have no supporting evidence and are not recommended for further consideration at this stage.
To proceed, the following is needed:
- Singapore package insert (HSA) warnings, contraindications and approved indication
- Mechanism of action data (e.g. from DrugBank)
- Review of the GENEVIEVE phase II efficacy and safety results versus paclitaxel
- Search for registered phase II/III breast cancer trials of cabazitaxel
- Safety plan addressing myelosuppression, hepatic impairment and CYP3A-related interactions
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.