Temozolomide
| Evidence Level: L1 | Predicted Indications: 2 |
Table of Contents
Temozolomide: From Malignant Glioma to Adult Astrocytic Tumour
One-Sentence Summary
Temozolomide is an oral alkylating agent long recognised as standard-of-care chemotherapy for glioblastoma and anaplastic astrocytoma, though no original indication text or UK licence is recorded in this Evidence Pack. The TxGNN model predicts it may be effective for Adult Astrocytic Tumour, with 2 clinical trials and 20 publications currently supporting this direction. Because astrocytic tumours are the same disease family as glioblastoma, this result most likely reflects confirmation of an already-established use rather than a genuinely new repurposing signal.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in this Evidence Pack (no licences on file); commonly known pharmacologically as malignant glioma (glioblastoma / anaplastic astrocytoma) |
| Predicted New Indication | Adult Astrocytic Tumour |
| TxGNN Prediction Score | 99.36% |
| Evidence Level | L1 |
| UK Market Status | Not marketed (per this dataset) |
| Number of Marketing Authorisations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in this Evidence Pack (Data Gap DG002), and no original indication is recorded in the regulatory dataset used to build this pack (original_indications is empty and no UK licences are on file). Based on well-established pharmacological knowledge, temozolomide is an oral second-generation alkylating agent of the imidazotetrazine class. It is spontaneously hydrolysed to the active metabolite MTIC, which methylates guanine residues in tumour DNA, ultimately triggering apoptosis in dividing cells. It is internationally recognised as a cornerstone treatment for glioblastoma multiforme and anaplastic astrocytoma.
Because “adult astrocytic tumour” is essentially the same disease category as glioblastoma/anaplastic astrocytoma, this TxGNN prediction should be interpreted as a confirmation of a well-established indication rather than a genuinely novel repurposing signal. The large body of completed Phase 3 RCTs identified below reflects decades of established clinical practice rather than emerging evidence for a new use.
Mechanistically, DNA alkylation is a broadly applicable cytotoxic mechanism across glial tumour subtypes, which is consistent with both the very high TxGNN prediction score (99.36%) and the depth of clinical evidence retrieved.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT00052455 | Phase 3 | Completed | 500 | Randomised trial comparing temozolomide alone with PCV (procarbazine, lomustine, vincristine) in recurrent WHO Grade III/IV astrocytic tumours |
| NCT00960492 | Phase 1 | Completed | 26 | Dose-finding study of cabozantinib (XL184) combined with temozolomide and radiotherapy in newly diagnosed glioblastoma |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 15758009 | 2005 | RCT | N Engl J Med | Landmark EORTC-NCIC trial establishing concomitant and adjuvant temozolomide plus radiotherapy as standard of care for newly diagnosed glioblastoma |
| 19269895 | 2009 | RCT | Lancet Oncol | 5-year follow-up of the EORTC-NCIC trial confirming durable survival benefit of temozolomide-radiotherapy in glioblastoma |
| 26670971 | 2015 | RCT | JAMA | EF-14 trial: Tumor Treating Fields plus maintenance temozolomide improved survival versus temozolomide alone |
| 30782343 | 2019 | RCT | Lancet | CeTeG/NOA-09 Phase 3 trial: lomustine-temozolomide combination superior to temozolomide alone in MGMT-methylated glioblastoma |
| 22578793 | 2012 | RCT | Lancet Oncol | NOA-08 Phase 3 trial comparing temozolomide alone versus radiotherapy alone in elderly patients with malignant astrocytoma |
| 24552317 | 2014 | RCT | N Engl J Med | RTOG 0825 Phase 3 trial: adding bevacizumab to standard temozolomide/radiotherapy did not improve overall survival in newly diagnosed glioblastoma |
| 40779733 | 2025 | RCT | J Clin Oncol | NRG BN007 Phase II/III trial of dual immune checkpoint blockade with temozolomide-based therapy in MGMT-unmethylated glioblastoma |
| 36809318 | 2023 | Review | JAMA | Review of glioblastoma and other primary brain malignancies in adults, covering temozolomide-based standard treatment |
| 29075865 | 2017 | Review | Curr Oncol Rep | Review of glioblastoma treatment strategies in older adults, including temozolomide regimens |
| 10914698 | 2000 | Review | Clin Cancer Res | Early review establishing temozolomide’s role in the treatment of malignant glioma |
UK Market Information
No UK marketing authorisation records are present in this Evidence Pack. Market status is recorded as Not marketed, with 0 licences on file. This should be independently verified against the MHRA Products database and the current BNF before any decision is finalised.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (alkylating agent, imidazotetrazine class) |
| Myelosuppression Risk | High — dose-limiting neutropenia and thrombocytopenia are well-recognised class effects; formal toxicity data is not available in this Evidence Pack (Data Gap DG001) |
| Emetogenicity Classification | Moderate |
| Monitoring Items | Full blood count with differential (including platelets), monitored regularly during and after each cycle; liver and renal function |
| Handling Protection | Must be handled in accordance with cytotoxic drug handling regulations (COSHH / local NHS cytotoxic handling SOPs) |
Safety Considerations
Please refer to the SmPC and BNF for safety information. Report suspected adverse reactions via the Yellow Card Scheme.
A Blocking data gap (DG001) has been identified: MHRA-approved label warnings/contraindications for this product are not currently available, which prevents completion of the S1 safety pre-assessment stage.
Conclusion and Next Steps
Decision: Hold
Rationale: A blocking data gap (missing label warnings/contraindications) prevents completion of the safety pre-assessment, and this dataset shows no confirmed UK marketing authorisation for temozolomide. In addition, “adult astrocytic tumour” substantially overlaps with the drug’s already-established clinical use, so this result carries lower incremental repurposing value despite strong (L1) trial evidence.
To proceed, the following is needed:
- MHRA-approved SmPC / Patient Information Leaflet for temozolomide (warnings, contraindications, drug interactions)
- Confirmation of current UK marketing authorisation status and licence number(s)
- Clarification of the originally licensed indication, to properly assess whether this represents a novel repurposing opportunity or confirmation of existing use
- Completion of mechanism-of-action documentation (Data Gap DG002)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.