Dasatinib

Evidence Level: L2

Predicted Indications: 9

Dasatinib

Pharmacist Assessment Report

Dasatinib: From Chronic Myelogenous Leukemia to Ewing Sarcoma

One-Sentence Summary

Dasatinib is a multi-targeted tyrosine kinase inhibitor, originally used to treat BCR-ABL1-positive chronic myelogenous leukemia (including blast phase). The TxGNN model predicts it may be effective for Ewing sarcoma, with 2 related clinical trials and 10 publications compiled for this direction. The evidence is mostly preclinical or early-phase, and the clinical signal is not confirmed.

Quick Overview

Item	Content
Original Indication	Chronic myelogenous leukemia, BCR-ABL1 positive (including blast phase)
Predicted New Indication	Ewing sarcoma
TxGNN Prediction Score	0.9990
Evidence Level	L2 (as assigned in the compiled data; see the note below)
Canada Market Status	Marketed (marketed DINs on record: at least 20)
Number of DINs	at least 20
Recommended Decision	Hold (research question)

Note on evidence level: The L2 label rests on one completed Phase 2 trial in mixed advanced sarcomas. That trial cannot isolate Ewing-specific efficacy, and a review reports that dasatinib failed as a single agent in Ewing sarcoma and rhabdomyosarcoma. In practice, the support for this indication is closer to preclinical or early exploratory evidence.

Why is This Prediction Reasonable?

Detailed mechanism-of-action data is not available in the data compiled for this report. From the literature, dasatinib is an oral inhibitor of BCR-ABL and SRC-family kinases. It also acts on c-KIT and PDGFR.

Preclinical work shows that SRC/FAK signaling drives invasion, migration and invadopodia formation in Ewing sarcoma. In cell lines, dasatinib has antiproliferative and antimigratory activity against Ewing sarcoma. The mechanism is plausible, but clinical confirmation is lacking. A review notes that single-agent dasatinib did not work in Ewing sarcoma or rhabdomyosarcoma in a Phase 2 study. This suggests that any benefit would more likely come from combinations, such as the RIST regimen (rapamycin, irinotecan, dasatinib, temozolomide).

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00788125	Phase 1/2	Terminated	7	Pediatric trial of dasatinib plus ifosfamide, carboplatin and etoposide. Terminated early, so it yields little efficacy or safety information.
NCT00464620	Phase 2	Completed	366	Single-agent dasatinib in advanced sarcomas, assessing response rate and 6-month progression-free survival. Mixed subtypes, so Ewing-specific efficacy cannot be separated.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
35655525	2022	Review	Sarcoma	Targeting FAK-Src in DSRCT, Ewing sarcoma and rhabdomyosarcoma. Notes single-agent dasatinib failed in a Phase 2 study of these subtypes.
42804591	2026	Case series	J Pediatr Hematol Oncol	Single-center descriptive series of the RIST regimen (including dasatinib) in relapsed Ewing sarcoma.
26170970	2015	Review	Oncol Lett	Src signaling as a potential drug target in sarcoma.
18202781	2008	Preclinical (in vitro)	Oncol Rep	Dasatinib has antiproliferative and antimigratory activity in neuroblastoma and Ewing sarcoma cell lines.
17363602	2007	Preclinical (in vitro)	Cancer Res	Dasatinib inhibits migration and invasion in sarcoma lines and induces 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.
35190971	2022	Review	Curr Treat Options Oncol	Systemic therapy for chondrosarcoma. Only indirectly related to Ewing sarcoma.

Canada Market Information

The compiled data lists 20 valid single-ingredient licences (none cancelled). Dosage form and approved-indication text were not available for any of them. The five main authorizations are shown below.

DIN	Product Name	Dosage Form	Approved Indication
02293137	SPRYCEL	Not available	Not available
02293129	SPRYCEL	Not available	Not available
02360810	SPRYCEL	Not available	Not available
02320193	SPRYCEL	Not available	Not available
02470713	APO-DASATINIB	Not available	Not available

Generic versions are also licensed under the TARO-, TEVA-, REDDY- and APO- brand names.

Cytotoxicity

Item	Content
Cytotoxicity Classification	Targeted therapy (multi-kinase inhibitor), not a conventional cytotoxic agent
Myelosuppression Risk	Please refer to the package insert warnings and precautions. The knowledge-graph contraindications include thrombocytopenia, neutropenia, agranulocytosis and anemia, so blood counts need close attention.
Emetogenicity Classification	Please refer to the package insert warnings and precautions
Monitoring Items	Complete blood count, liver function, ECG/QT interval, and signs of fluid retention (pleural or pericardial effusion)
Handling Protection	Please refer to the package insert warnings and precautions

Safety Considerations

Contraindications (from the TxGNN knowledge graph, not label text):
- Cardiac: long QT syndrome (including familial), torsades de pointes, congestive heart failure, heart failure, myocardial infarction, coronary thrombosis, pericardial effusion, hemopericardium.
- Haematological: thrombocytopenia, neutropenia, agranulocytosis, anemia (including macrocytic), hemoglobinopathy.
- Other: liver disease, gallbladder disease, active peptic ulcer disease, intracerebral hemorrhage.
Drug Interactions (100 interactions recorded; examples):
- Major: famotidine, ranitidine, cimetidine, omeprazole, rabeprazole (acid-suppressing agents that may reduce dasatinib absorption), clarithromycin, dexamethasone, acetylsalicylic acid.
- Moderate: hydrocortisone, budesonide, loperamide, aprepitant, bisacodyl, magnesium oxide, aluminum hydroxide, calcium carbonate, saxagliptin.
Reported adverse events: the literature describes pleural effusion and, rarely, chylothorax with dasatinib.

Package insert warnings and contraindications were not available. Please refer to the package insert for the authoritative safety information.

Conclusion and Next Steps

Decision: Hold (research question)

Rationale: The mechanism is plausible, since SRC/FAK signaling is relevant to Ewing sarcoma and dasatinib is active in cell lines. However, the only completed clinical trial enrolled mixed sarcoma subtypes, and published reports indicate single-agent dasatinib failed in Ewing sarcoma. Supporting clinical data is limited to a small terminated trial and a single-center case series of a combination regimen.

To proceed, the following is needed:

Ewing-specific clinical data, preferably from combination regimens such as RIST, and from subtype-level analysis of the Phase 2 sarcoma trial.
Package insert warnings and contraindications from Health Canada, which are a blocking gap for safety screening.
Detailed mechanism-of-action data from DrugBank.
A safety plan covering QT prolongation, cytopenias and fluid retention, particularly for a paediatric and young-adult population.

Other predicted indications, for context:

Predicted Indication	Evidence Level	Recommendation
Myeloid leukemia	L1	Proceed with Guardrails. Largely reflects the existing CML label. A reported Phase 3 trial in core-binding-factor AML is the new element, so restrict to molecularly defined subtypes.
Liposarcoma	L4	Hold. Preclinical SRC data only.
Dermatofibrosarcoma protuberans	L5	Hold. Plausible PDGFR mechanism, but imatinib is the established option.
Ovarian myxoid liposarcoma; ganglioneuroblastoma; gingival fibromatosis; and 3 others	L5	Hold. Model prediction only.

Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.