Temozolomide
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
Temozolomide: From Anaplastic Astrocytoma and Glioblastoma to Adult Astrocytic Tumour
One-Sentence Summary
Temozolomide is an oral alkylating chemotherapy, originally used for anaplastic astrocytoma, astrocytoma (excluding glioblastoma) and glioblastoma. The TxGNN model predicts it may be effective for adult astrocytic tumour, with 2 clinical trials and 20 publications compiled for this prediction, including several randomised Phase 3 trials. This prediction largely overlaps with the drug's existing uses, so it is better viewed as confirmation of current use than as true repurposing.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Anaplastic astrocytoma, astrocytoma (excluding glioblastoma), brain glioblastoma (from the knowledge graph; Singapore licence entries list no indication text) |
| Predicted New Indication | Adult astrocytic tumour |
| TxGNN Prediction Score | 99.36% |
| Evidence Level | L1 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 8 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the compiled data. From the supporting analysis, temozolomide is an oral alkylating agent that methylates DNA (at O6-guanine, N7-guanine and N3-adenine). This causes cytotoxic DNA lesions and apoptosis. Its effect is greatest in tumours with a methylated MGMT promoter, because MGMT is the main enzyme that repairs this damage.
The predicted indication, adult astrocytic tumour, falls within the same disease family as the drug's existing uses (anaplastic astrocytoma and glioblastoma). The same DNA-damage mechanism applies, and the standard chemoradiation regimen (radiotherapy plus concomitant and adjuvant temozolomide, the "Stupp regimen") is supported by Phase 3 and randomised evidence. The prediction is therefore mechanistically reasonable, but it confirms existing use rather than opening a new disease area.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00052455 | Phase 3 | Completed | 500 | Randomised comparison of temozolomide versus PCV (procarbazine, lomustine, vincristine) in recurrent WHO grade III and IV astrocytic tumours; direct evidence in this tumour type |
| NCT00960492 | Phase 1 | Completed | 26 | Dose-finding of XL184 (cabozantinib) with temozolomide and radiotherapy in first-line glioblastoma; safety-focused, does not test temozolomide efficacy |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 15758009 | 2005 | RCT | N Engl J Med | Radiotherapy plus concomitant and adjuvant temozolomide versus radiotherapy alone in glioblastoma (efficacy and safety) |
| 19269895 | 2009 | RCT long-term follow-up | Lancet Oncol | 5-year analysis of the EORTC-NCIC trial of chemoradiation with temozolomide in glioblastoma |
| 22578793 | 2012 | RCT (Phase 3) | Lancet Oncol | NOA-08: dose-dense temozolomide alone versus radiotherapy alone in elderly patients with anaplastic astrocytoma or glioblastoma |
| 30782343 | 2019 | RCT (Phase 3) | Lancet | CeTeG/NOA-09: lomustine plus temozolomide versus standard temozolomide in MGMT-methylated glioblastoma |
| 26670971 | 2015 | RCT | JAMA | Tumour-treating fields plus maintenance temozolomide versus temozolomide alone in glioblastoma |
| 29260225 | 2017 | RCT | JAMA | Tumour-treating fields plus maintenance temozolomide versus temozolomide alone, effect on survival in glioblastoma |
| 24552317 | 2014 | RCT | N Engl J Med | Adding bevacizumab to standard temozolomide chemoradiation in newly diagnosed glioblastoma |
| 39480453 | 2024 | RCT | JAMA Oncol | Adding veliparib to temozolomide in MGMT-methylated glioblastoma |
| 34898238 | 2022 | Guideline | J Clin Oncol | ASCO-SNO guideline on therapy for diffuse astrocytic and oligodendroglial tumours in adults |
| 27668386 | 2016 | Review | Clin J Oncol Nurs | Overview of glioblastoma disease and treatment |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN11707P | TEMODAL Capsule 100 mg | Capsule | Not stated in the licence data |
| SIN11706P | TEMODAL Capsule 20 mg | Capsule | Not stated in the licence data |
| SIN15710P | TemoRel Hard Capsule 20 mg | Capsule | Not stated in the licence data |
| SIN15709P | TemoRel Hard Capsule 100 mg | Capsule | Not stated in the licence data |
| SIN15066P | ASTRODAL Capsules 100 mg | Capsule | Not stated in the licence data |
Three further licences are valid: ASTRODAL Capsules 20 mg (SIN15067P), GLIOTEM 100 Capsule 100 mg (SIN15642P) and GLIOTEM 20 Capsule 20 mg (SIN15641P). All 8 licences are valid single-ingredient oral capsules, and none is cancelled.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (alkylating agent) |
| Myelosuppression Risk | Medium to high; the knowledge graph lists neutropenia, thrombocytopenia, pancytopenia, anaemia, lymphopenia and aplastic anaemia as contraindicated conditions, which points to marrow toxicity as a key concern |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Complete blood count with differential, liver function, renal function |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Safety Considerations
- Contraindication signals (from the knowledge graph, not label text): liver failure, thrombocytopenia, neutropenia, agranulocytosis, anaemia, macrocytic anaemia, pneumocystosis, pancytopenia, lymphopenia, myelodysplastic syndrome, idiopathic aplastic anaemia, aplastic anaemia.
- Drug Interactions: the interaction query found 100 potential interacting drugs. The most notable is naltrexone (Moderate). Levofloxacin is rated Minor. Others, such as pantoprazole, omeprazole, lansoprazole, morphine, metformin, prednisone, hydrocortisone, amphotericin B and doxycycline, are of unknown severity.
Please refer to the package insert for official warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Multiple randomised Phase 3 trials and RCTs, including the EORTC-NCIC chemoradiation trial and NOA-08, support temozolomide in astrocytic tumours. The predicted indication overlaps with its established uses, and the drug is already marketed in Singapore with 8 valid licences. The main reservations are myelosuppression risk, resistance linked to MGMT status, and the absence of indication text in the licence data.
To proceed, the following is needed:
- Review of the HSA package insert, to confirm approved indications, warnings and contraindications
- Detailed mechanism of action data from DrugBank
- Molecular stratification (MGMT promoter methylation, IDH status) to guide patient selection
- A haematological monitoring plan, with attention to patients who have pre-existing marrow suppression or liver impairment
- A review of the interacting drug list against typical co-medications
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.