Dasatinib
| Evidence Level: L3 | Predicted Indications: 9 |
Table of Contents
Dasatinib: Ewing sarcoma
One-Sentence Summary
Dasatinib is an oral multi-targeted kinase inhibitor that blocks BCR-ABL and SRC-family kinases. The TxGNN model predicts it may be relevant to Ewing sarcoma, with a score of 0.9990. Support comes from 2 clinical trials (one small terminated trial and one completed Phase 2 sarcoma trial), a small case series of a dasatinib-containing regimen, and preclinical work. Evidence level is L3, and no randomized trial exists.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Ewing sarcoma |
| TxGNN Prediction Score | 0.9990 |
| Evidence Level | L3 |
| India Market Status | Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data |
| Number of Listed Products | at least 20 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available in the data compiled for this report. Based on known information, dasatinib is a kinase inhibitor that acts on BCR-ABL, SRC-family kinases, c-KIT and PDGFR.
In Ewing sarcoma, preclinical studies show that SRC activity drives invadopodia formation, migration and invasion, especially under microenvironmental stress. Dasatinib inhibited migration, invasion and proliferation in sarcoma and Ewing sarcoma cell lines, and induced apoptosis in bone sarcoma cells that depend on SRC. The FAK-Src axis has been proposed as a therapeutic target in Ewing sarcoma and related tumours.
Clinical support is weaker. A review notes that single-agent dasatinib failed in the Ewing sarcoma and rhabdomyosarcoma subtypes of a Phase 2 advanced-sarcoma study. The remaining interest lies mainly in combination approaches, such as the RIST regimen (rapamycin, irinotecan, dasatinib, temozolomide), which has been used in relapsed disease.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00464620 | Phase 2 | Completed | 366 | Dasatinib in advanced sarcomas; response rate and 6-month progression-free survival were assessed. It included a Ewing sarcoma cohort, but Ewing-specific results are not shown in the data compiled. |
| NCT00788125 | Phase 1/2 | Terminated | 7 | Pediatric trial of dasatinib with ifosfamide, carboplatin and etoposide. Stopped early with very few patients, so it provides minimal safety or efficacy information. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 35655525 | 2022 | Review | Sarcoma | Targeting FAK-Src in desmoplastic small round cell tumours, Ewing sarcoma and rhabdomyosarcoma; single-agent dasatinib failed in the Ewing sarcoma and rhabdomyosarcoma subtypes of a Phase 2 study. |
| 42804591 | 2026 | Case series | J Pediatr Hematol Oncol | Descriptive single-centre experience with the RIST regimen (including dasatinib) in relapsed Ewing sarcoma. |
| 26170970 | 2015 | Review | Oncol Lett | Role of Src signaling in sarcoma and its feasibility as a drug target. |
| 18202781 | 2008 | Preclinical (in vitro) | Oncol Rep | Dasatinib showed antiproliferative and antimigratory activity in neuroblastoma and Ewing sarcoma cell lines. |
| 17363602 | 2007 | Preclinical (in vitro) | Cancer Res | Dasatinib inhibited migration and invasion in sarcoma cell lines and induced apoptosis in SRC-dependent bone sarcoma cells. |
| 27566104 | 2016 | Preclinical (in vitro) | Neoplasia | Microenvironmental stress activates Src-dependent invadopodia and migration in Ewing sarcoma. |
| 31521948 | 2019 | Preclinical (in vitro) | Neoplasia | Tenascin C and Src cooperate to promote invadopodia formation in Ewing sarcoma. |
India Market Information
At least 20 valid single-ingredient licences are recorded (none cancelled); this list may be partial. Main examples:
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 67898 | Dasamed 20mg Tablet | Bottle of 60 tablets | Not recorded |
| 66154 | Dyronib 20mg Tablet | Bottle of 60 tablets | Not recorded |
| 200644 | Sprycel 50mg Tablet | Bottle of 60 tablets | Not recorded |
| 154992 | Nextki 70mg Tablet | Bottle of 60 tablets | Not recorded |
| 28832 | Beedan 70mg Tablet | Bottle of 60 tablets | Not recorded |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (tyrosine kinase inhibitor) |
| Myelosuppression Risk | Medium to high; neutropenia, thrombocytopenia and anaemia are listed as concerns |
| Emetogenicity Classification | Low |
| Monitoring Items | Complete blood count with differential, liver function, cardiac assessment including QT interval, signs of fluid retention or pleural/pericardial effusion |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Conditions of concern (listed as contraindications in the data compiled, not from label text): long QT syndrome (including familial), torsades de pointes, liver disease, gallbladder disease, thrombocytopenia, neutropenia, agranulocytosis, anaemia, congestive heart failure and heart failure, myocardial infarction, coronary thrombosis, active peptic ulcer disease, intracerebral haemorrhage, pericardial effusion, haemopericardium and haemoglobinopathy.
- Drug Interactions: 691 interactions were found. Major ones include acid-reducing agents (famotidine, ranitidine, cimetidine, omeprazole, rabeprazole), dexamethasone, acetylsalicylic acid and clarithromycin. Moderate ones include antacids (aluminium hydroxide, calcium carbonate, magnesium oxide), hydrocortisone, budesonide, loperamide, aprepitant and saxagliptin.
Package insert warnings and contraindications were not available; please consult the package insert.
Conclusion and Next Steps
Decision: Hold
Rationale:
- The evidence level is L3. A Phase 2 sarcoma trial (NCT00464620) included a Ewing sarcoma cohort, and a small case series (PMID 42804591) used a dasatinib-containing regimen in relapsed disease. No randomized trial exists, and a review reports that single-agent dasatinib failed in the Ewing sarcoma subtype, so the signal is mostly preclinical and combination-based.
To proceed, the following is needed:
- Ewing-specific outcomes from NCT00464620
- Prospective data on dasatinib-containing combinations such as RIST
- Detailed mechanism-of-action data
- Package insert warnings and contraindications from the Indian labels
- A safety monitoring plan, especially for cardiac, haematological and fluid-retention risks
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.