Paclitaxel
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Paclitaxel: From Ovarian Cancer to Female Breast Carcinoma
One-Sentence Summary
Paclitaxel is a microtubule-stabilizing taxane chemotherapy, originally used for ovarian cancer. The TxGNN model predicts it may be effective for female breast carcinoma, with 40 clinical trials and 20 publications currently supporting this direction. Paclitaxel is already an established standard-of-care taxane in breast cancer, so this is closer to a label-adjacent indication than true repurposing.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Ovarian cancer (the approved indication text in the Singapore licence records is empty) |
| Predicted New Indication | Female breast carcinoma |
| TxGNN Prediction Score | 99.995% |
| Evidence Level | L2 (as assigned in the compiled data; Phase 3 trials exist but are mostly combination or backbone studies) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 14 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data are not available in the data compiled for this report. Based on known pharmacology, paclitaxel stabilizes microtubules and blocks disassembly of the mitotic spindle. This causes G2/M arrest and apoptosis in rapidly dividing tumour cells.
This mechanism does not depend on hormone-receptor signalling. It therefore applies to ovarian cancer and to breast cancer alike, including ER-negative and triple-negative disease, where chemotherapy is a mainstay. Older reviews (1997–2002) describe paclitaxel and docetaxel as evidence-based components of therapy for advanced breast and ovarian carcinoma, and paclitaxel was licensed in the USA for adjuvant treatment of node-positive early breast cancer.
Other breast-related predictions in the same ranking show a similar pattern. ER-negative disease and ER-positive disease (mainly high-risk or endocrine-resistant settings) have the strongest support. Hormone-resistant disease has moderate support. Bilateral and nipple carcinoma rest on case reports only. Ehrlich tumour is a mouse model, not a human indication.
Clinical Trial Evidence
The compiled data list 40 trials for this indication. The table shows the 10 most relevant, prioritizing completed trials in which paclitaxel is a core component.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00003539 | Phase 2 | Completed | 50 | Weekly paclitaxel plus trastuzumab in metastatic breast cancer; directly tests paclitaxel |
| NCT00006120 | Phase 2 | Unknown | Not reported | Randomized comparison of two schedules of docetaxel or paclitaxel in metastatic breast cancer |
| NCT00006459 | Phase 3 | Completed | Not reported | Gemcitabine plus paclitaxel vs paclitaxel alone in recurrent or metastatic breast cancer |
| NCT00075270 | Phase 3 | Completed | 580 | Lapatinib plus paclitaxel vs paclitaxel alone as first-line therapy for advanced or metastatic breast cancer |
| NCT00553358 | Phase 3 | Completed | 455 | Neo-ALTTO: neoadjuvant lapatinib and/or trastuzumab plus paclitaxel in HER2-positive breast cancer |
| NCT00513292 | Phase 3 | Completed | 280 | Neoadjuvant FEC then paclitaxel plus trastuzumab vs the reverse sequence in HER2-positive breast cancer |
| NCT00431080 | Phase 3 | Completed | 478 | Dose-dense adjuvant FE75C followed by docetaxel vs paclitaxel in node-positive breast cancer |
| NCT01822314 | Phase 3 | Completed | 632 | ETNA: neoadjuvant nab-paclitaxel vs solvent-based paclitaxel in HER2-negative high-risk breast cancer |
| NCT00667251 | Phase 3 | Completed | 652 | Taxane-based chemotherapy plus lapatinib vs trastuzumab as first-line therapy for HER2-positive metastatic breast cancer |
| NCT00002826 | Phase 2 | Completed | 36 | Pilot study of PSC 833 to modulate multidrug resistance to paclitaxel in metastatic breast cancer |
Most Phase 3 trials use paclitaxel as a chemotherapy backbone, and the investigational question is the added agent. They support paclitaxel's established role in breast cancer but do not isolate its own effect.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 10791395 | 2000 | Review | Lancet | Taxanes (paclitaxel, docetaxel) are evidence-based components of therapy for advanced breast, lung and ovarian cancer; paclitaxel approved in the USA for adjuvant node-positive breast cancer |
| 9282422 | 1997 | Review | Drug and Therapeutics Bulletin | Review of paclitaxel and docetaxel in breast and ovarian cancer; licence extended to metastatic breast carcinoma |
| 11147586 | 2000 | Phase 2 trial | Cancer | Doxorubicin plus paclitaxel in advanced breast carcinoma; importance of prior adjuvant anthracycline therapy |
| 11745249 | 2001 | Review | Cancer | Role of paclitaxel in multimodality treatment of inflammatory breast carcinoma |
| 9296218 | 1997 | Dose-finding study | Annals of Oncology | Maximum tolerable doses of paclitaxel (3-hour infusion) with cyclophosphamide in advanced breast cancer |
| 10898354 | 2000 | Review | Cancer | Developments in breast cancer chemotherapy |
| 24823476 | 2014 | Genomic study | Nature Communications | TEKT4 germline variations enriched after treatment and linked to breast cancer resistance to paclitaxel |
| 39317691 | 2024 | Computational/preclinical | Chemical Biology & Drug Design | Paclitaxel combinations against breast carcinoma and in vivo biomarkers |
| 20665703 | 2011 | Preclinical | Journal of Cellular Physiology | ZD6474 enhances paclitaxel antiproliferative and apoptotic effects in breast carcinoma cells |
| 31515668 | 2019 | Preclinical | Cancer Chemotherapy and Pharmacology | SRSF3 downregulation sensitizes breast cancer cells to paclitaxel |
The literature is mostly older reviews and early-phase studies, plus preclinical work on resistance and sensitization. No Phase 3 publication is directly listed for this disease entry.
Singapore Market Information
Paclitaxel has 14 valid single-ingredient registrations in Singapore and no cancelled ones. All are injectable forms. Approved indication text is not recorded for any of them. The table lists 5 of the 14.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN16436P | PACLITERO 100 Solution for Injection 100mg/16.7ml | Injection, solution | Not recorded |
| SIN12050P | GENEXOL Injection 6 mg/ml | Injection | Not recorded |
| SIN14532P | ABRAXANE for Injectable Suspension 100mg/vial | Injection, powder, for suspension | Not recorded |
| SIN14102P | PAXEL Injection 6 mg/ml | Injection, solution, concentrate | Not recorded |
| SIN13752P | Aclipak Concentrate for Solution for Infusion 6mg/ml | Infusion, solution concentrate | Not recorded |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (taxane, antimitotic microtubule stabilizer) |
| Myelosuppression Risk | High. Neutropenia is the expected dose-limiting effect; the knowledge-graph contraindication list includes neutropenia, agranulocytosis, thrombocytopenia and anaemia |
| Emetogenicity Classification | Low |
| Monitoring Items | CBC with differential, liver and renal function, peripheral neuropathy, hypersensitivity reactions during infusion |
| Handling Protection | Must follow cytotoxic drug handling regulations. Please also refer to the package insert warnings and precautions |
Safety Considerations
Package insert warnings and contraindications were not available in the data compiled for this report. Please refer to the package insert for these.
- Disease contraindications from the knowledge graph (not label text): These include neutropenia, agranulocytosis, thrombocytopenia, anaemia, liver disease, kidney disease, peripheral neuropathy, myocardial infarction, sudden cardiac arrest, asthma, diabetes mellitus and hyperbilirubinaemia. They should be treated as signals needing verification against the label.
- Drug Interactions: The interaction screen returned 100 interactions in total. The first 20 listed are mostly moderate: aprepitant, cimetidine, clarithromycin, clotrimazole, dexamethasone, eliglustat, metronidazole, miconazole, rolapitant, rosuvastatin, simvastatin, tinidazole and troglitazone. Ascorbic acid and levofloxacin are minor. Glimepiride, doxycycline, morphine, metformin and omeprazole are of unknown severity.
- Reported adverse events in the literature: These include paclitaxel-induced pneumonitis, uveitis, corneal epithelial lesions, taxane-induced polyneuropathy and chemotherapy-related amenorrhoea.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Paclitaxel is already a standard taxane in breast cancer. Multiple Phase 2 trials and several completed Phase 3 trials use it as a core component, and it is marketed in Singapore in 14 registrations. The evidence does not isolate paclitaxel's own effect in the Phase 3 studies, and the supporting reviews are old. The recommendation is therefore to proceed with guardrails, not a full Go.
To proceed, the following is needed:
- Package insert warnings and contraindications from HSA (a blocking gap for safety screening)
- Detailed mechanism-of-action data from DrugBank
- Confirmation of the approved indications on Singapore labels, which are currently blank in the data
- Verification of the knowledge-graph contraindications against the label, especially for patients with baseline neutropenia, thrombocytopenia, anaemia, hepatic impairment or neuropathy
- Subtype-specific guidance, since endocrine therapy plus CDK4/6 inhibition is often preferred over chemotherapy in ER-positive disease
- A monitoring plan for myelosuppression, neuropathy and infusion hypersensitivity
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.