Nilotinib
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
- Nilotinib
- Pharmacist Assessment Report
- Nilotinib: From Chronic Myelogenous Leukaemia (BCR-ABL1 Positive) to Dermatofibrosarcoma Protuberans
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Australia Market Information
- Cytotoxicity
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Nilotinib: From Chronic Myelogenous Leukaemia (BCR-ABL1 Positive) to Dermatofibrosarcoma Protuberans
One-Sentence Summary
Nilotinib is a kinase inhibitor originally used to treat BCR-ABL1-positive chronic myelogenous leukaemia. The TxGNN model predicts it may be effective for dermatofibrosarcoma protuberans (DFSP), but currently only 1 review article supports this direction, with no registered clinical trials for this specific disease.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Chronic myelogenous leukaemia, BCR-ABL1 positive |
| Predicted New Indication | Dermatofibrosarcoma protuberans |
| TxGNN Prediction Score | 0.9931 |
| Evidence Level | L5 |
| 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 | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on the known pharmacology of nilotinib, it inhibits BCR-ABL and also inhibits platelet-derived growth factor receptors (PDGFR).
DFSP is driven by the COL1A1-PDGFB gene fusion, which causes autocrine activation of PDGFRB. Because nilotinib inhibits PDGFR in addition to BCR-ABL, there is a plausible mechanistic link between its action in leukaemia and in DFSP.
However, the only supporting item is a 2018 review of small-molecule PDGFR inhibitors. Clinical evidence in DFSP relates mainly to imatinib, and no nilotinib-specific trial is listed. The prediction is therefore mechanistically reasonable but clinically unproven.
Clinical Trial Evidence
Currently no related clinical trials registered for dermatofibrosarcoma protuberans.
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT02587169 | Phase 1/2 | Unknown | 40 | Nilotinib plus doxorubicin as neoadjuvant treatment in retroperitoneal liposarcoma and leiomyosarcoma (GEIS-27); not specific to DFSP |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 29408302 | 2018 | Review | Pharmacological Research | Reviews small-molecule PDGFR inhibitors in neoplastic disorders, supporting the PDGFR-targeting rationale |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 12858R | Tasigna | Capsule 200 mg (as hydrochloride monohydrate) | Not available in the compiled data |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (tyrosine kinase inhibitor) |
| Myelosuppression Risk | Medium (neutropenia, thrombocytopenia and anaemia are listed as contraindication-related conditions in the knowledge graph) |
| Emetogenicity Classification | Low |
| Monitoring Items | FBC, liver function, electrolytes (potassium, magnesium, calcium, phosphate), blood glucose, ECG (QT interval) |
| Handling Protection | Please refer to the Product Information (PI) warnings and precautions |
Safety Considerations
- Conditions flagged in the knowledge graph (not label text): hypertension, long QT syndrome and torsades de pointes, liver disease, gallbladder disease, pancreatitis, thrombocytopenia, neutropenia, anaemia, hyperglycaemia and diabetes, hypokalaemia, hypercalcaemia, hypophosphataemia, and hyperbilirubinaemia (including Gilbert syndrome).
- Drug Interactions: 100 interactions were identified. Major interactions include:
- Dexamethasone
- Clarithromycin
- Picosulfuric acid
- Polyethylene glycol (3350 with electrolytes)
Moderate interactions include acid-suppressing drugs (famotidine, ranitidine, cimetidine, omeprazole, rabeprazole), other corticosteroids (hydrocortisone, betamethasone, budesonide, triamcinolone), pioglitazone, loperamide, bupropion, aprepitant, bisacodyl and saxagliptin.
- Literature safety signal: A case report describes pancreatic carcinoma developing after nilotinib therapy for CML. This is a single case and does not establish causation.
Please refer to the TGA-approved Product Information (PI) for authoritative warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The mechanistic rationale (PDGFRB activation in DFSP) is strong, but the evidence consists only of a general review, with no nilotinib-specific trials in DFSP. Clinical support for PDGFR inhibition in DFSP comes from imatinib, so nilotinib’s role remains a research question.
To proceed, the following is needed:
- Nilotinib-specific clinical data in DFSP (case series or trials), and comparison with imatinib
- Detailed mechanism of action data
- TGA Product Information warnings and contraindications, including the approved indication text for ARTG 12858R
- A cardiac safety plan (QT monitoring and interaction management) for any oncology use outside CML
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.