Docetaxel
| Evidence Level: L2 | Predicted Indications: 7 |
Table of Contents
Docetaxel: Ewing sarcoma
One-Sentence Summary
Docetaxel is a taxane chemotherapy agent that stabilises microtubules and stops rapidly dividing cells from completing division. The TxGNN model predicts it may be useful for Ewing sarcoma. This direction is supported by 8 registered clinical trials and 20 publications, mostly Phase 2 studies of docetaxel combined with gemcitabine or irinotecan in relapsed or refractory disease.
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 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| 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. Docetaxel is a member of the taxane class. Taxanes stabilise microtubules, which blocks cell division and can kill rapidly proliferating tumour cells. This general mechanism is plausible against sarcoma cells.
In published work, docetaxel is rarely used alone in Ewing sarcoma. It is mainly paired with gemcitabine (GEMDOX) or irinotecan for relapsed or refractory disease.
- A Phase 2 study of sequential gemcitabine followed by docetaxel included recurrent Ewing sarcoma and osteosarcoma.
- A Phase 1/2 study evaluated docetaxel plus irinotecan in children and young adults with recurrent or refractory Ewing sarcoma family tumours.
- A small Phase 2 study tested single-agent docetaxel in relapsed and refractory Ewing’s tumours.
Response rates in these studies appear modest, and the regimens are used in salvage settings. Docetaxel’s independent contribution is therefore unclear.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT00073983 | Phase 2 | Completed | 54 | Sequential gemcitabine then docetaxel in recurrent Ewing sarcoma, osteosarcoma and chondrosarcoma; directly relevant |
| NCT03449901 | Phase 2 | Completed | 98 | ADI-PEG 20 plus gemcitabine and docetaxel in sarcomas including Ewing sarcoma; the added agent confounds docetaxel’s contribution |
| NCT00002825 | Phase 2 | Completed | 20 | Single-agent docetaxel in children with recurrent solid tumours, including Ewing sarcoma; small, mixed population |
| NCT02511132 | Phase 2 | Completed | 22 | Vigil immunotherapy versus gemcitabine plus docetaxel in metastatic Ewing’s sarcoma; docetaxel role not clearly defined |
| NCT00014456 | Phase 1 | Completed | 35 | Dose escalation of docetaxel, gemcitabine and filgrastim in advanced solid tumours; safety-focused |
| NCT00049296 | Phase 1 | Completed | 26 | Thalidomide plus docetaxel pharmacokinetics in advanced cancer; limited relevance to Ewing sarcoma |
| NCT05116800 | Phase 2 | Withdrawn | 0 | 9-ING-41 plus gemcitabine/docetaxel in advanced sarcoma; no data |
| NCT04183062 | Phase 2 | Withdrawn | 0 | BIO-11006 plus gemcitabine/docetaxel for lung metastases in osteosarcoma or Ewing’s sarcoma; no data |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 22363068 | 2012 | Phase 2 trial | The Oncologist | Gemcitabine followed by docetaxel in recurrent Ewing sarcoma, osteosarcoma and chondrosarcoma (SARC003); primary endpoint was RECIST response |
| 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 1/2 trial | BMC Cancer | Docetaxel plus irinotecan in recurrent or refractory Ewing sarcoma family tumours |
| 18521364 | 2003 | Phase 2 trial | Sarcoma | Initial results of docetaxel in 14 patients with relapsed or refractory Ewing’s tumours |
| 18484657 | 2008 | Clinical study | Cancer | Gemcitabine plus docetaxel toxicity and efficacy in children and young adults with refractory bone sarcoma |
| 22302783 | 2012 | Cohort | Pediatr Blood Cancer | GEMDOX in relapsed and refractory paediatric sarcomas |
| 19727011 | 2009 | Clinical report | J Pediatr Hematol Oncol | Gemcitabine-docetaxel in relapsed or refractory paediatric sarcomas |
| 28221727 | 2017 | Single-centre experience | Pediatr Blood Cancer | Docetaxel, bevacizumab and gemcitabine in very high-risk sarcomas in adolescents and young adults |
| 15117993 | 2004 | Preclinical/clinical | J Clin Oncol | Synergy of sequential gemcitabine then docetaxel in cell culture and in sarcoma patients |
| 26154614 | 2015 | Preclinical | Pediatr Blood Cancer | Docetaxel and cabazitaxel tested against paediatric preclinical models |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 10148D | Docetaxel Accord | Solution concentrate for I.V. infusion, 80 mg in 4 mL | Not stated in the data compiled |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (taxane class) |
| Myelosuppression Risk | High; neutropenia is the principal concern, and thrombocytopenia and anaemia may also occur |
| Emetogenicity Classification | Low to moderate |
| Monitoring Items | Full blood count with differential, liver function including bilirubin, renal function |
| Handling Protection | Must follow cytotoxic drug handling requirements |
Please refer to the Product Information (PI) for full warnings and precautions.
Safety Considerations
Label-based warnings and contraindications are not available in the data compiled for this report. Please refer to the TGA-approved Product Information (PI).
- Conditions of concern (not taken from label text): liver disease, gallbladder disease, hyperbilirubinaemia (including Gilbert syndrome), thrombocytopenia, neutropenia, agranulocytosis, anaemia, peripheral neuropathy and other neuritis, diarrhoeal disease, stomatitis, pulmonary oedema and cardiac tamponade.
- Drug interactions: the interaction screen returned 100 potential interactions. Examples of the interacting drugs identified:
- Major: clarithromycin.
- Moderate: aprepitant, rolapitant, cimetidine, metronidazole, tinidazole, miconazole, eliglustat, rosuvastatin, simvastatin and troglitazone.
- Minor: dexamethasone, prednisolone, prednisone and levofloxacin.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Several Phase 2 trials and studies include docetaxel in relapsed or refractory Ewing sarcoma, which supports an evidence level of L2. However, docetaxel is mostly given in combination, response rates are modest, and the populations are small and mixed. The independent benefit of docetaxel is therefore unproven.
To proceed, the following is needed:
- Mechanism of action data and a clearer assessment of docetaxel’s independent contribution within gemcitabine and irinotecan combinations
- Review of the TGA-approved Product Information for warnings, contraindications and dosing in paediatric and young adult patients
- A haematological, hepatic and neuropathy monitoring plan, with management of interacting medicines such as clarithromycin
- Confirmation of the current Australian regulatory position for use in Ewing sarcoma, and an appropriate trial or specialist sarcoma-centre pathway
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.