Nilotinib
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
- Nilotinib
- Nilotinib: From Chronic Myelogenous Leukaemia (BCR-ABL1 positive) to Dermatofibrosarcoma Protuberans
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 this top-ranked prediction currently has no registered clinical trials and only 1 review article supporting it. Among the other predictions, liposarcoma has the most supporting evidence (1 Phase I/II trial and 1 Phase I publication).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Chronic myelogenous leukaemia, BCR-ABL1 positive (the Singapore licence records contain no indication text, so this comes from the knowledge graph) |
| Predicted New Indication | Dermatofibrosarcoma protuberans |
| TxGNN Prediction Score | 99.31% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Hold |
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, nilotinib is a kinase inhibitor that targets BCR-ABL and also inhibits PDGFR. Its efficacy in BCR-ABL1-positive chronic myelogenous leukaemia is established, and mechanistically it may be applicable to tumours driven by PDGFR signalling.
DFSP is driven by the COL1A1-PDGFB fusion, which causes constitutive activation of PDGFR-beta. Because nilotinib inhibits PDGFR, there is a plausible mechanistic rationale. Imatinib is the established PDGFR-directed therapy for DFSP, so nilotinib would be a class-level extension rather than a new concept. The only supporting item is a 2018 review of PDGFR small-molecule inhibitors, and there is no direct clinical evidence for nilotinib in DFSP in the data provided.
Other predicted indications (for context):
| Rank | Predicted Indication | Score | Evidence Level | Support |
|---|---|---|---|---|
| 2 | Liposarcoma | 98.85% | L3 | 1 Phase I/II trial, 1 Phase I publication (nilotinib + doxorubicin) |
| 3 | Ovarian myxoid liposarcoma | 98.74% | L5 | Prediction only |
| 4 | Ewing sarcoma | 98.45% | L5 | Only a bioinformatic prognostic study that does not evaluate nilotinib |
| 9 | Fibroblastic neoplasm | 96.90% | L4 | Class-level PDGFR/KIT rationale (mostly imatinib and preclinical studies) |
| 5–8, 10 | Ganglioneuroblastoma, heart fibrosarcoma, a rare vertebral/endocrine/T-cell syndrome, kidney fibrosarcoma, conventional fibrosarcoma | 96.8–97.0% | L5 | Prediction only |
Clinical Trial Evidence
No clinical trials are registered for dermatofibrosarcoma protuberans. The closest related trial, found under the rank 2 prediction (liposarcoma), is shown below for reference.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02587169 | Phase 1/2 | Unknown | 40 | GEIS-27: nilotinib plus doxorubicin as neoadjuvant treatment in retroperitoneal liposarcoma and leiomyosarcoma. No efficacy results are available in the data provided. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 29408302 | 2018 | Review | Pharmacological Research | Reviews small-molecule PDGFR inhibitors in neoplastic disorders (supports DFSP rationale, does not test nilotinib directly) |
| 30037815 | 2018 | Phase I trial | Clinical Cancer Research | Nilotinib (400 mg twice daily) with doxorubicin in sarcomas; early feasibility and safety data (liposarcoma prediction) |
| 35150408 | 2023 | Systematic review | Musculoskeletal Surgery | Medical treatments for progressive desmoid tumours (fibroblastic neoplasm prediction) |
| 28282612 | 2017 | Phase 2 trial (imatinib) | European Journal of Cancer | Imatinib induced sustained progression arrest in progressive desmoid tumours; nilotinib was not tested |
| 26455322 | 2016 | Preclinical | Oncogene | PDGFRB mutants in infantile myofibromatosis are oncogenic and imatinib-sensitive |
| 35689379 | 2022 | Preclinical | J Cell Mol Med | Penttinen syndrome PDGFRB variant causes aberrant constitutive STAT1 signalling |
| 26376592 | 2015 | Case report | Turk J Haematol | Pancreatic carcinoma developing after nilotinib therapy for CML; a safety signal, not efficacy evidence |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN13498P | Tasigna Capsule 200mg | Capsule | Not stated in the licence record |
| SIN13959P | Tasigna Capsule 150mg | Capsule | Not stated in the licence record |
Both licences are valid single-ingredient oral products (manufacturers: Novartis Pharma Stein AG and Novartis Pharmaceutical Manufacturing LLC).
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (tyrosine kinase inhibitor) |
| Myelosuppression Risk | Medium. Knowledge-graph contraindication edges include neutropenia, thrombocytopenia, anaemia and agranulocytosis. |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | CBC with differential, liver function, electrolytes (potassium, phosphorus, calcium), glucose, pancreatic enzymes, ECG for QT interval |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Contraindications (knowledge-graph signals, not label text): long QT syndrome (including familial) and torsades de pointes, hypertension, liver disease, hyperbilirubinaemia (including Gilbert syndrome), gallbladder disease, pancreatitis, diabetes mellitus and diabetic ketoacidosis, hyperglycaemia, potassium deficiency, hypercalcaemia, nephrocalcinosis, phosphorus metabolism disease and hypophosphataemia, thrombocytopenia, neutropenia, agranulocytosis, and anaemia (including macrocytic).
- Drug Interactions: 100 interactions were identified. Major-level examples include dexamethasone, clarithromycin, picosulfuric acid and polyethylene glycol (3350 with electrolytes). Moderate-level examples include acid-suppressing agents (famotidine, ranitidine, cimetidine, omeprazole, rabeprazole), other corticosteroids (hydrocortisone, betamethasone, budesonide, triamcinolone), pioglitazone, loperamide, bupropion, aprepitant, bisacodyl and saxagliptin.
- Other signal: one case report describes pancreatic carcinoma after nilotinib therapy. It is a single case and does not establish causality.
Package insert warnings were not available in the data compiled for this report, so please refer to the package insert for the full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The DFSP prediction has a plausible PDGFR-based mechanism, but its only support is a single review, with no nilotinib-specific clinical data, and imatinib is already the established option. Among the other predictions, liposarcoma has the most evidence (L3), but its Phase I/II trial has unknown status and no efficacy results. The safety profile, including QT prolongation signals and many drug interactions, calls for caution.
To proceed, the following is needed:
- Package insert warnings and contraindications from the HSA website (a blocking gap for safety screening)
- Mechanism of action data from DrugBank
- Case series or trial data for nilotinib in DFSP, including head-to-head or post-imatinib comparisons
- Efficacy results from NCT02587169 and the Phase II portion of the liposarcoma programme
- A QT, hepatic and drug-interaction monitoring plan for any sarcoma population
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.