Dasatinib
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Dasatinib: From Chronic Myeloid Leukemia to Ewing Sarcoma
One-Sentence Summary
Dasatinib is an oral tyrosine kinase inhibitor originally used for BCR-ABL1-positive chronic myeloid leukemia (CML), including the blast phase. The TxGNN model predicts it may be effective for Ewing sarcoma, with 2 clinical trials and 10 publications compiled for this report. The supporting evidence is mostly laboratory-based, and the one clinical review that addresses it reports that single-agent dasatinib failed in this tumor type.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Chronic myelogenous leukemia, BCR-ABL1 positive (including blast phase). The Singapore licence records contain no indication text, so this comes from the knowledge-graph indication data. |
| Predicted New Indication | Ewing sarcoma |
| TxGNN Prediction Score | 99.90% |
| Evidence Level | L4 (see the note below) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 6 |
| Recommended Decision | Hold |
Evidence level note: the only completed Phase 2 trial is a single-arm study in mixed sarcomas, not an RCT, so it does not meet the L2 criterion. The Ewing-specific support is preclinical, with one review and one small case series, so L4 is the more accurate grading.
Why is This Prediction Reasonable?
Dasatinib is a multi-targeted kinase inhibitor. It was designed to block BCR-ABL and SRC-family kinases, and it also acts on c-KIT and PDGFR. Detailed mechanism-of-action data were not available in the data compiled for this report. The description above is based on the published literature.
Its action in CML comes from blocking BCR-ABL. In Ewing sarcoma the relevant target is different: SRC-family kinases. Laboratory studies show that SRC activity drives invasion, migration and invadopodia formation in Ewing sarcoma cells. In bone sarcoma cell lines that depend on SRC for survival, dasatinib reduced migration and invasion and induced apoptosis. Reviews therefore describe the Src/FAK pathway as a plausible target in Ewing sarcoma and related sarcomas.
This link has not been confirmed clinically. A review notes that in a Phase 2 study of advanced sarcomas, single-agent dasatinib failed in the Ewing sarcoma and rhabdomyosarcoma subtypes. Any realistic role would therefore be in combination, for example the RIST regimen (rapamycin, irinotecan, dasatinib, temozolomide) described in a recent case series.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00788125 | Phase 1/2 | Terminated | 7 | Pediatric study of dasatinib with ifosfamide, carboplatin and etoposide in sarcoma-type tumors. Enrollment was very small, so it gives minimal safety or efficacy information. |
| NCT00464620 | Phase 2 | Completed | 366 | Single-agent dasatinib in advanced sarcomas, measuring response rate and 6-month progression-free survival. It was a mixed-sarcoma population, and no results are available here. A later review reports it failed in the Ewing sarcoma and rhabdomyosarcoma subtypes. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 35655525 | 2022 | Review | Sarcoma | Targeting the FAK-Src complex in DSRCT, Ewing sarcoma and rhabdomyosarcoma. Notes that single-agent dasatinib failed in Ewing sarcoma and rhabdomyosarcoma in a Phase 2 study. |
| 26170970 | 2015 | Review | Oncology Letters | Src signaling in sarcoma and the feasibility of Src as a drug target. |
| 35190971 | 2022 | Review | Current Treatment Options in Oncology | Systemic therapy for chondrosarcoma. Related bone sarcoma, with only indirect relevance. |
| 42804591 | 2026 | Case series | Journal of Pediatric Hematology/Oncology | Single-center descriptive experience with the RIST regimen (rapamycin, irinotecan, dasatinib, temozolomide) in relapsed Ewing sarcoma. |
| 18202781 | 2008 | In vitro | Oncology Reports | Dasatinib showed antiproliferative and antimigratory activity in neuroblastoma and Ewing sarcoma cell lines. |
| 17363602 | 2007 | In vitro | Cancer Research | Dasatinib inhibited migration and invasion in diverse sarcoma cell lines and induced apoptosis in SRC-dependent bone sarcoma cells. |
| 27566104 | 2016 | In vitro | Neoplasia | Microenvironmental stress activates Src-dependent invadopodia and migration in Ewing sarcoma. |
| 31521948 | 2019 | In vitro | Neoplasia | Tenascin C and Src cooperate to promote invadopodia formation in Ewing sarcoma. |
Singapore Market Information
Six oral film-coated tablet registrations are valid. The licence records contain no approved-indication text. The first five are listed below:
| Authorization Number | Product Name | Dosage Form |
|---|---|---|
| SIN13352P | SPRYCEL Tablets 70 mg (AstraZeneca) | Tablet, film coated |
| SIN17175P | MYOPHIL Film Coated Tablets 70 mg (Biocon) | Tablet, film coated |
| SIN13354P | SPRYCEL Tablets 50 mg (AstraZeneca) | Tablet, film coated |
| SIN17177P | MYOPHIL Film Coated Tablets 50 mg (Biocon) | Tablet, film coated |
| SIN17176P | MYOPHIL Film Coated Tablets 20 mg (Biocon) | Tablet, film coated |
A sixth registration, SPRYCEL Tablets 20 mg (SIN13353P), is also valid.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (multi-kinase inhibitor), not a conventional cytotoxic agent |
| Myelosuppression Risk | Medium to high. Neutropenia, thrombocytopenia and anemia are flagged in the knowledge-graph safety data. |
| Emetogenicity Classification | Low |
| Monitoring Items | Complete blood count with differential, liver function, and QT interval and cardiac status. Also watch for pleural effusion and bleeding. |
| Handling Protection | Please refer to the package insert warnings and precautions. |
Safety Considerations
- Conditions flagged in the knowledge graph (not label text): long QT syndrome and torsades de pointes, congestive heart failure and myocardial infarction, liver disease, thrombocytopenia, neutropenia and agranulocytosis, anemia, intracerebral hemorrhage, active peptic ulcer disease, and pericardial effusion.
- Drug Interactions (100 interacting drugs recorded; main ones listed):
- Major: the acid-suppressing drugs famotidine, ranitidine, cimetidine, omeprazole and rabeprazole, plus dexamethasone, acetylsalicylic acid and clarithromycin.
- Moderate: hydrocortisone, budesonide, loperamide, aprepitant, bisacodyl, saxagliptin, and antacids and laxatives such as aluminum hydroxide, calcium carbonate, magnesium oxide and polyethylene glycol.
Label-based warnings and contraindications were not available in the data compiled for this report. Please refer to the package insert for these.
Conclusion and Next Steps
Decision: Hold
Rationale: The mechanistic link through SRC signaling is plausible and consistent across laboratory studies. However, the only clinical evidence is a mixed-sarcoma Phase 2 study that reportedly failed in Ewing sarcoma, plus a terminated 7-patient trial and a small case series. This does not justify advancing dasatinib as a single agent in Ewing sarcoma.
For context, the model's second-ranked prediction, myeloid leukemia, is largely an on-label use of dasatinib. It has Phase 3 support, including the DASISION 5-year results and a Phase 3 trial in core-binding factor AML, so it is not true repurposing.
To proceed, the following is needed:
- Subtype-specific results from the advanced sarcoma Phase 2 trial, including the Ewing sarcoma cohort.
- Clinical data on rational combinations (for example, RIST-type regimens) beyond a single-center case series.
- Package insert warnings, contraindications and mechanism-of-action data to complete the safety review.
- A plan for monitoring hematologic and cardiac toxicity and managing drug interactions, especially with acid-suppressing drugs, in a pediatric and young adult population.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.