Ixabepilone
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Ixabepilone: From Breast Carcinoma to Ewing Sarcoma
One-Sentence Summary
Ixabepilone is an epothilone B analog (a microtubule-stabilizing chemotherapy) originally used to treat breast carcinoma. The TxGNN model predicts it may be effective for Ewing sarcoma, with 2 clinical trials (1 Phase 1, 1 Phase 2) and 1 publication currently supporting this direction. The evidence is early and does not yet show a clear benefit in Ewing sarcoma specifically.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Breast carcinoma / breast neoplasm (the licence text on file for India is blank) |
| Predicted New Indication | Ewing sarcoma |
| TxGNN Prediction Score | 0.9976 |
| Evidence Level | L5 |
| India Market Status | Listed in a compiled Indian medicine price dataset (2 of 2) – CDSCO approval status is not included in this data |
| Number of Listed Products | 2 (valid: 2) |
| Recommended Decision | Hold (treat as a research question) |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known information, ixabepilone is an epothilone B analog that stabilizes microtubules, causing mitotic arrest and cell death in rapidly dividing cells. Its efficacy in breast carcinoma is established, and mechanistically it may be applicable to Ewing sarcoma.
Ewing sarcoma is an aggressive, highly proliferative tumour, so an antimitotic agent is plausible. Unlike taxanes, ixabepilone is less affected by some resistance mechanisms, including P-glycoprotein-mediated efflux. It may therefore retain activity in chemoresistant disease. Preclinical pediatric xenograft models resistant to paclitaxel also showed activity.
The very high TxGNN score agrees with the early clinical signal. However, the main support is a Phase 2 trial in a mixed refractory solid tumour population of children and young adults. The published literature does not show a clear objective response benefit in Ewing sarcoma.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00331643 | Phase 2 | Completed | 120 | Efficacy of ixabepilone in children and young adults with refractory solid tumours, including Ewing sarcoma. This is the most relevant trial, but the cohort is mixed and Ewing-specific results need to be checked. |
| NCT00030108 | Phase 1 | Completed | 30 | Dose-finding and pharmacokinetic study in paediatric patients with refractory solid tumours and leukaemia. It informs safety and dosing, not Ewing sarcoma efficacy. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 20068084 | 2010 | Phase II trial (single-arm) | Clin Cancer Res | Ixabepilone given daily for 5 days in children and young adults with refractory solid tumours (Children’s Oncology Group). Neutropenia was the main dose-limiting toxicity, and the study assessed response rates across six tumour strata. |
India Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| Registration No. 111143 | Ixempra 15mg Injection (BMS India Pvt Ltd) | Vial of 1 injection | Not stated in the data |
| Registration No. 111336 | Ixempra 45mg Injection (BMS India Pvt Ltd) | Vial of 1 injection | Not stated in the data |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (epothilone, microtubule stabilizer) |
| Myelosuppression Risk | High (neutropenia was the main dose-limiting toxicity in paediatric studies) |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | CBC with differential, liver function, and neuropathy assessment |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Safety Considerations
- Contraindications / risk conditions (from the TxGNN model (deep learning), not label text; these may reflect similarities the model learned between related diseases, not biological evidence): liver failure and liver disease, hyperbilirubinaemia (including Gilbert syndrome), gallbladder disease, thrombocytopenia, neutropenia, agranulocytosis, anaemia, peripheral neuropathy and other peripheral nervous system disease, heart disease (including coronary artery disease, myocardial ischaemia, heart conduction disease and sudden cardiac arrest), cardiovascular disease, diabetes mellitus and diabetic ketoacidosis.
- Drug Interactions: 276 interactions were identified. The major-level ones include deferiprone and samarium (153Sm) lexidronam. Moderate-level ones include aprepitant, dexamethasone, cimetidine, clarithromycin, clotrimazole, metronidazole, miconazole, rosuvastatin, simvastatin, tinidazole, troglitazone, cobicistat, deferasirox, palifermin, strontium chloride Sr-89, fostamatinib, lusutrombopag and chloroquine. Many of these likely involve CYP3A4 or myelosuppression effects.
- Known toxicity from the literature: Peripheral neuropathy is usually mild to moderate, sensory and cumulative. Neutropenia is the main dose-limiting toxicity.
The package insert warnings for the India products were not available, so please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold (treat as a research question)
Rationale: The evidence is L2. It rests on one completed Phase 2 trial in a mixed refractory paediatric and young-adult solid tumour population and a supporting Phase 1 study. Neither shows Ewing sarcoma-specific efficacy, and the literature does not show a clear objective response benefit. Safety screening cannot proceed without the India package insert.
To proceed, the following is needed:
- Ewing sarcoma-specific response data from NCT00331643 and the Children’s Oncology Group study (PMID 20068084)
- India package insert warnings and contraindications (a blocking gap for safety screening)
- Detailed mechanism of action data (MOA) from DrugBank
- A safety monitoring plan for paediatric and young-adult patients, covering neutropenia, neuropathy and hepatic impairment
Other predicted indications: The remaining nine predictions (salivary gland-type breast cancer, breast papillomatosis, breast leiomyoma, breast lipoma, diabetic mastopathy, giant adenofibroma of the breast, benign neoplasm of male breast, subareolar duct papillomatosis and infiltrating nipple syringomatous adenoma) are at L5 with Hold recommendations. They have no supporting trials, and the literature listed for benign neoplasm of male breast concerns malignant disease and does not support that indication. Most are benign conditions where the toxicity of a cytotoxic agent is not justified. The high scores come from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.