Docetaxel
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
Docetaxel: From Non-Small Cell Lung Cancer to Female Breast Carcinoma
One-Sentence Summary
Docetaxel is a taxane chemotherapy drug originally used for non-small cell lung cancer, prostate cancer, head and neck cancer, gastric cancer and breast cancer. The TxGNN model predicts it may be effective for female breast carcinoma, but breast carcinoma is already among its established indications, so this is confirmation of known use rather than true repurposing. The data compiled for this report include 50 clinical trials and 20 publications for this indication.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Non-small cell lung cancer (the Singapore licence records contain no approved indication text; original indications are taken from the knowledge-graph indication list) |
| Predicted New Indication | Female breast carcinoma (already a known indication) |
| TxGNN Prediction Score | 99.90% |
| Evidence Level | L1 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 12 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available in the data compiled for this report. Based on general knowledge, docetaxel is a taxane that stabilises microtubules and blocks cell division (mitosis). This is the basis of its cytotoxic activity in rapidly dividing tumour cells such as breast carcinoma cells.
Breast carcinoma and breast neoplasm are already listed among docetaxel's original indications. The high TxGNN score (0.999) is therefore consistent with known use. The evidence below is established-use evidence, not evidence for a new indication.
Other predicted indications are far weaker. Ewing sarcoma and rhabdomyosarcoma have small Phase II or combination-regimen data only. The remaining predictions (well-differentiated fetal adenocarcinoma of the lung, small cell lung carcinoma, primary pulmonary lymphoma, pulmonary blastoma and several rhabdomyosarcoma subtypes) have no supporting efficacy evidence or only case reports, and are recommended as "Hold".
Clinical Trial Evidence
The table lists the most relevant trials from the data: completed trials graded as directly relevant, followed by large completed Phase 3 trials.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00003519 | Phase 3 | Completed | 2778 | Adjuvant doxorubicin/docetaxel vs doxorubicin/cyclophosphamide in node-positive or high-risk node-negative breast cancer |
| NCT00021255 | Phase 3 | Completed | 3222 | AC followed by docetaxel (AC-T), with or without trastuzumab, vs docetaxel/carboplatin/trastuzumab in HER2-positive adjuvant setting |
| NCT00003782 | Phase 3 | Completed | 5351 | Three adjuvant regimens (AC-T, AT, ATC) in node-positive breast cancer |
| NCT00002707 | Phase 3 | Completed | 2411 | Preoperative AC with or without docetaxel (before or after surgery) in operable breast cancer |
| NCT00333775 | Phase 3 | Completed | 736 | Bevacizumab plus docetaxel vs docetaxel plus placebo, first-line HER2-negative metastatic breast cancer |
| NCT00887536 | Phase 3 | Completed | 1613 | Docetaxel/cyclophosphamide (TC) plus bevacizumab vs TC alone vs TAC in early breast cancer |
| NCT00667251 | Phase 3 | Completed | 652 | Taxane chemotherapy plus lapatinib vs trastuzumab in HER2-positive metastatic breast cancer |
| NCT03588091 | Phase 3 | Completed | 355 | Neoadjuvant pyrotinib vs placebo with trastuzumab and docetaxel in HER2-positive breast cancer |
| NCT00321633 | Phase 2 | Completed | 148 | Randomised comparison of carboplatin vs docetaxel in metastatic genetic (BRCA) breast cancer |
| NCT00003352 | Phase 2 | Completed | 89 | Doxorubicin, docetaxel and cyclophosphamide in locally advanced or metastatic breast cancer |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 28398846 | 2017 | RCT | J Clin Oncol | ABC trials: docetaxel/cyclophosphamide (TC) compared with taxane plus anthracycline regimens in early breast cancer |
| 10791395 | 2000 | Review | Lancet | Taxanes (paclitaxel and docetaxel) are evidence-based components of therapy for advanced breast, lung and ovarian cancer |
| 9282422 | 1997 | Review | Drug Ther Bull | Review of paclitaxel and docetaxel in breast and ovarian cancer |
| 18624687 | 2008 | Review | Expert Opin Drug Metab Toxicol | Lessons from the development of docetaxel |
| 12868800 | 2003 | Review | Breast Cancer Res Treat | Docetaxel-anthracycline combinations in metastatic breast cancer |
| 9775340 | 1998 | Review | Am J Health Syst Pharm | Pharmacology, trials and adverse effects of docetaxel in metastatic breast cancer |
| 12868802 | 2003 | Review | Breast Cancer Res Treat | Neoadjuvant docetaxel in locally advanced breast cancer |
| 16020974 | 2005 | Phase II | Oncology | Weekly docetaxel plus gemcitabine as first-line treatment for metastatic breast cancer |
| 12599222 | 2003 | Phase II | Cancer | Capecitabine with docetaxel and epirubicin as first-line therapy in advanced breast carcinoma |
| 27997437 | 2017 | Retrospective | Anti-Cancer Drugs | Association between adjuvant docetaxel-based chemotherapy and breast cancer-related lymphedema |
Singapore Market Information
All 12 registrations are valid single-ingredient products. No approved indication text is available in the data for any of them.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN14106P | Taxotere Concentrate for Solution for Infusion 20mg/ml | Infusion, solution concentrate | Not available |
| SIN14107P | Taxotere Concentrate for Solution for Infusion 80mg/4ml | Infusion, solution concentrate | Not available |
| SIN14218P | Hospira Docetaxel Concentrate for Solution for Infusion 20 mg / 2 ml | Infusion, solution | Not available |
| SIN14564P | Docetaxel Sandoz Concentrate for Solution for Infusion 10mg/ml | Injection, solution, concentrate | Not available |
| SIN15109P | Daxotel Concentrate for Solution for Infusion 20mg/ml | Injection, solution, concentrate | Not available |
Seven further registrations exist (Hospira 80 mg/8 ml, Textas 20 and 80, Docetaxel Advagen, Docehope 20 mg/ml and 80 mg/4 ml, Docetaxel Stada). All products are injectable.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (taxane, antimicrotubule agent) |
| Myelosuppression Risk | High. The knowledge graph links docetaxel with neutropenia, thrombocytopenia, anaemia and agranulocytosis |
| Emetogenicity Classification | Low to moderate (based on general drug-class knowledge) |
| Monitoring Items | Complete blood count with differential, liver function (including bilirubin), renal function, signs of neuropathy, fluid retention and mucositis |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Safety Considerations
- Contraindications / conditions of concern (from knowledge-graph links, not label text): liver disease, gallbladder disease, thrombocytopenia, neutropenia, agranulocytosis, peripheral neuropathy and other peripheral nervous system diseases, anaemia, hyperbilirubinaemia (including Gilbert syndrome), diarrhoeal disease, pulmonary oedema, stomatitis, neuritis (including motor nerve neuritis) and cardiac tamponade.
- Drug Interactions: 100 interactions were identified. The main ones listed are:
- Major: clarithromycin.
- Moderate: aprepitant, rolapitant, cimetidine, metronidazole, tinidazole, miconazole, eliglustat, rosuvastatin, simvastatin and troglitazone.
- Minor: dexamethasone, prednisolone, prednisone and levofloxacin.
Package insert warnings and contraindications have not been obtained. Please refer to the package insert for authoritative safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Docetaxel's use in breast carcinoma is supported by multiple large completed Phase 3 trials (several with thousands of patients), so the evidence is strong, and the drug is already marketed in Singapore under 12 registrations. This is established use, not new repurposing. Safety is not fully characterised from label text, and the drug carries high myelosuppression risk.
To proceed, the following is needed:
- Singapore package insert warnings, contraindications and approved indication text for each registration
- Detailed mechanism-of-action data from DrugBank
- A safety monitoring plan covering myelosuppression, hepatic impairment, neuropathy and the major clarithromycin interaction
- For the other predicted indications (Ewing sarcoma, rhabdomyosarcoma, pulmonary tumours), indication-specific evidence before further consideration. Currently they remain "Research Question" or "Hold".
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.