Dactinomycin
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Dactinomycin
- Dactinomycin: From Ewing Sarcoma and Other Solid Tumours to Relapsing-Remitting Multiple Sclerosis
Dactinomycin: From Ewing Sarcoma and Other Solid Tumours to Relapsing-Remitting Multiple Sclerosis
One-Sentence Summary
Dactinomycin is a cytotoxic antibiotic-class chemotherapy drug, originally used for Ewing sarcoma, rhabdomyosarcoma, Wilms tumour, testicular germ cell tumours and gestational trophoblastic neoplasm. The TxGNN model's top-ranked prediction is relapsing-remitting multiple sclerosis, but no clinical trials and no publications support it, so it is a purely computational signal. The better-supported predictions are rhabdomyosarcoma subtypes and sites, which largely extend an existing standard-of-care use rather than represent true repurposing.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Ewing sarcoma, testicular germ cell tumours, gestational trophoblastic neoplasm, rhabdomyosarcoma, Wilms tumour (the Singapore licence has no indication text recorded) |
| Predicted New Indication | Relapsing-remitting multiple sclerosis (rank 1) |
| TxGNN Prediction Score | 99.58% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Dactinomycin is generally known as a DNA-intercalating agent that inhibits transcription. This produces strong cytotoxic effects in rapidly dividing cells, and it also has immunosuppressive potential.
For relapsing-remitting multiple sclerosis, the mechanistic link is weak. Dactinomycin has no established role in MS, and its toxicity profile (myelosuppression, hepatic toxicity) is unfavourable for a chronic autoimmune disease that needs long-term treatment. The very high score (0.996) is best read as a computational artefact, not a clinical lead.
The next nine predictions are more credible but need careful reading:
- Rhabdomyosarcoma subtypes and sites (vaginal botryoid, extrahepatic bile duct, parameningeal, prostate): dactinomycin is a core component of the VA/VAC regimens used for rhabdomyosarcoma. These are mostly site- or subtype-specific extensions of an existing use.
- Liver sarcoma, upper aerodigestive tract neoplasm, head and neck cancer: the supporting papers concern paediatric sarcomas (for example undifferentiated embryonal sarcoma of the liver and head and neck rhabdomyosarcoma). They do not support dactinomycin for common adult epithelial cancers such as squamous cell carcinoma.
- T-cell leukaemia: the only trial is a Phase 3 in adult acute lymphoblastic leukaemia whose title shows no dactinomycin arm. The two publications are in vitro drug-resistance models.
Clinical Trial Evidence
Clinical trials were found only for the T-cell leukaemia prediction (rank 10). No trials are registered for the top-ranked prediction, relapsing-remitting multiple sclerosis.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00002766 | Phase 3 | Completed | 170 | Ara-C/high-dose mitoxantrone vs a vincristine/prednisone-based regimen as induction in adult acute lymphoblastic leukaemia; dactinomycin is not evidently an investigated agent, so this is not direct evidence |
Literature Evidence
Relapsing-remitting multiple sclerosis has no related literature. The table below lists the most relevant publications for the best-supported predictions (rhabdomyosarcoma and related sarcomas).
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 19770373 | 2009 | RCT (probable) | J Clin Oncol | COG D9803: VAC vs VAC alternating with vincristine/topotecan/cyclophosphamide in intermediate-risk rhabdomyosarcoma |
| 11408506 | 2001 | Trial report | J Clin Oncol | Intergroup Rhabdomyosarcoma Study IV: results of risk-based regimens in non-metastatic disease |
| 39058728 | 2024 | Trial report | Cancer | EpSSG RMS 2005: reduced-dose alkylator chemotherapy plus radiotherapy in incompletely resected standard-risk rhabdomyosarcoma |
| 33567392 | 2021 | Cohort | Eur J Cancer | EpSSG RMS2005: reduced chemotherapy in completely resected embryonal rhabdomyosarcoma |
| 22104356 | 2012 | Cohort | Int J Radiat Oncol Biol Phys | COG D9602: reduced-dose radiotherapy and local control in low-risk rhabdomyosarcoma |
| 12586800 | 2003 | Cohort | J Clin Oncol | Lessons from IRS-III and IV for non-orbital, non-parameningeal head and neck rhabdomyosarcoma |
| 37814737 | 2023 | Case series/review | Cureus | Undifferentiated embryonal sarcoma of the liver in a child treated with alternating chemotherapy that included dactinomycin |
| 15143082 | 2004 | Retrospective | J Clin Oncol | Age is a risk factor for hepatopathy with vincristine, dactinomycin and cyclophosphamide (VAC) |
| 21671362 | 2011 | Retrospective | Pediatr Blood Cancer | COG retrospective review of dactinomycin and vincristine toxicity in childhood cancer |
| 34900598 | 2022 | Case report/review | Urol Case Rep | Adult prostate embryonal rhabdomyosarcoma treated with dactinomycin, vincristine and cyclophosphamide; the patient died of the disease |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN10989P | K. U. Dactinomycin for Injection 0.5 mg/vial | Injection, powder, for solution | Not recorded in the data compiled for this report |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (DNA-intercalating antitumour antibiotic) |
| Myelosuppression Risk | High. Knowledge-graph contraindication links include neutropenia, thrombocytopenia, leukopenia, anaemia, aplastic anaemia and agranulocytosis |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Complete blood count with differential, liver function (hepatopathy and hepatic veno-occlusive/Budd-Chiari-type events are documented with VAC), renal function |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Safety Considerations
- Package insert warnings and contraindications: not available in the data compiled for this report. Please refer to the package insert.
- Knowledge-graph contraindication links (not label text): liver disease, gallbladder disease, thrombocytopenia, neutropenia, agranulocytosis, anaemia, macrocytic anaemia, leukopenia, aplastic anaemia, idiopathic aplastic anaemia, varicella zoster infection, herpes zoster, hepatic vein thrombosis and Budd-Chiari syndrome.
- Drug interactions: 100 interactions were found. Notable ones:
- Major: deferiprone, samarium (153Sm) lexidronam
- Moderate: palifermin, strontium chloride Sr-89, fostamatinib, mercaptopurine, roflumilast, chloramphenicol
- Minor: levofloxacin
- Publication-based safety signals: hepatopathy with VAC (age is a risk factor), and late effects such as tooth agenesis in childhood cancer survivors.
Conclusion and Next Steps
Decision: Hold
Rationale:
- The top-ranked prediction (relapsing-remitting multiple sclerosis) has only a model score and no trials or literature. The mechanism does not fit a chronic autoimmune disease, and the toxicity profile is unfavourable.
- The rhabdomyosarcoma-related predictions have a sound biological basis, but they mainly reflect existing standard of care. The adult head and neck and leukaemia predictions have no direct dactinomycin evidence.
To proceed, the following is needed:
- Package insert warnings and contraindications (a blocking gap for safety screening)
- Mechanism of action data
- Indication text for the Singapore licence SIN10989P
- For rhabdomyosarcoma extensions, confirmation of whether the sites and subtypes are already covered by the approved rhabdomyosarcoma indication
- For any adult or non-sarcoma indication, dedicated efficacy evidence that includes dactinomycin as an investigated agent
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.