Docetaxel
| Evidence Level: L2 | Predicted Indications: 7 |
Table of Contents
Docetaxel: Microtubule-stabilizing taxane → Ewing sarcoma
One-Sentence Summary
Docetaxel is a taxane chemotherapy drug that stabilizes microtubules and is marketed in Canada as an injection. The TxGNN model predicts it may be effective for Ewing sarcoma, with 8 clinical trials and 20 publications compiled for this direction. Most of the evidence comes from docetaxel combinations (mainly with gemcitabine) in mixed sarcoma cohorts, so the Ewing-specific signal is hard to separate.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Ewing sarcoma |
| TxGNN Prediction Score | 0.9990 |
| Evidence Level | L2 |
| Canada Market Status | Marketed (marketed DINs: 3 of 3) |
| Number of DINs | 3 (marketed: 3) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data for docetaxel is not available in the data compiled for this report. Based on its known drug class, docetaxel is a taxane that stabilizes microtubules and blocks cell division, so it may affect rapidly proliferating sarcoma cells.
Laboratory and clinical work suggests that giving gemcitabine followed by docetaxel can have a synergistic cytotoxic effect in sarcoma (PMID 15117993). Phase 2 studies have tested this sequence, and docetaxel with irinotecan, in recurrent Ewing sarcoma.
An important limitation is that much of the evidence comes from mixed pediatric sarcoma cohorts, and efficacy in refractory disease appears modest. Ewing-specific benefit therefore remains uncertain.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00073983 | Phase 2 | Completed | 54 | Sequential gemcitabine then docetaxel in recurrent Ewing sarcoma, osteosarcoma, or chondrosarcoma |
| NCT02511132 | Phase 2 | Completed | 22 | Vigil immunotherapy vs gemcitabine plus docetaxel in metastatic Ewing sarcoma; docetaxel’s role is not clear from the title |
| NCT03449901 | Phase 2 | Completed | 98 | ADI-PEG 20 plus gemcitabine and docetaxel in sarcomas including Ewing sarcoma |
| NCT00002825 | Phase 2 | Completed | 20 | Single-agent docetaxel in children with recurrent solid tumors; Ewing patients are a subset |
| NCT00014456 | Phase 1 | Completed | 35 | Dose escalation of docetaxel, gemcitabine and filgrastim in advanced solid tumors (safety and dosing) |
| NCT00049296 | Phase 1 | Completed | 26 | Thalidomide plus docetaxel pharmacokinetics in advanced cancer; not Ewing-specific |
| NCT05116800 | Phase 2 | Withdrawn | 0 | 9-ING-41 with gemcitabine/docetaxel in sarcomas; no data generated |
| NCT04183062 | Phase 2 | Withdrawn | 0 | BIO-11006 with gemcitabine/docetaxel in osteosarcoma and Ewing sarcoma; no data generated |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 22363068 | 2012 | Phase 2 trial | The Oncologist | Sequential gemcitabine and docetaxel in recurrent Ewing sarcoma, osteosarcoma and chondrosarcoma (SARC003) |
| 28787430 | 2017 | Phase 2 trial | Br J Cancer | GEIS-21: intensive chemotherapy including gemcitabine and docetaxel in newly diagnosed high-risk Ewing sarcoma |
| 25164234 | 2014 | Phase 2 trial | BMC Cancer | Docetaxel plus irinotecan in recurrent or refractory Ewing sarcoma family tumors |
| 18521364 | 2003 | Phase 2 trial | Sarcoma | Docetaxel in relapsed and refractory Ewing’s tumours (14 patients, initial results) |
| 18484657 | 2008 | Cohort | Cancer | Gemcitabine plus docetaxel in children and young adults with refractory bone sarcoma |
| 22302783 | 2012 | Retrospective cohort | Pediatr Blood Cancer | GEMDOX in relapsed and refractory pediatric sarcomas |
| 19727011 | 2009 | Clinical report | J Pediatr Hematol Oncol | Gemcitabine-docetaxel in relapsed or refractory pediatric sarcomas |
| 15117993 | 2004 | Preclinical/clinical | J Clin Oncol | Synergistic cytotoxicity of gemcitabine followed by docetaxel in sarcoma |
| 26154614 | 2015 | Preclinical | Pediatr Blood Cancer | Pediatric Preclinical Testing Program comparison of cabazitaxel and docetaxel |
| 20132000 | 2010 | Review | Expert Rev Anticancer Ther | Role of chemotherapy in soft tissue sarcomas |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02458020 | DOCETAXEL INJECTION | Not recorded | Not recorded |
| 02361957 | DOCETAXEL INJECTION USP | Not recorded | Not recorded |
| 02439336 | DOCETAXEL INJECTION | Not recorded | Not recorded |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (taxane class) |
| Myelosuppression Risk | High (neutropenia, thrombocytopenia and anemia are relevant risks) |
| Emetogenicity Classification | Low to moderate |
| Monitoring Items | Complete blood count with differential, liver function (including bilirubin), renal function, signs of neuropathy, fluid retention |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Safety Considerations
- Conditions of concern (not label text): Contraindication relations recorded for docetaxel include liver disease, hyperbilirubinemia, neutropenia, thrombocytopenia, anemia, peripheral neuropathy, stomatitis, diarrheal disease, pulmonary edema and cardiac tamponade. The package insert should be checked to confirm the exact wording.
- Drug Interactions: 100 interactions are recorded. Major: clarithromycin. Moderate examples: aprepitant, cimetidine, metronidazole, miconazole, rolapitant, rosuvastatin, simvastatin, tinidazole, eliglustat, troglitazone. Minor examples: dexamethasone, prednisone, prednisolone, levofloxacin.
Please also refer to the package insert for full warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Several completed Phase 2 studies and publications have tested docetaxel-containing regimens in Ewing sarcoma, mostly in combination and in mixed sarcoma cohorts. Efficacy appears modest in refractory disease. The evidence is enough to justify a focused research question but not a routine-use recommendation. Because the cited Ewing-specific evidence is mostly from combination regimens, the L2 level should be read cautiously.
To proceed, the following is needed:
- Ewing-specific efficacy data separated from mixed sarcoma cohorts, ideally from a controlled study
- Package insert warnings and contraindications from Health Canada
- Detailed mechanism-of-action data
- A hematologic and hepatic monitoring plan, plus a review of interacting medications (especially strong CYP3A4 inhibitors such as clarithromycin)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.