Temozolomide

證據等級: L5

預測適應症: 2 個

Temozolomide: An Already-Established Agent Confirmed for Adult Astrocytic Tumour

One-Sentence Summary

Temozolomide is an oral alkylating agent within the imidazotetrazine class. The TxGNN model predicts high relevance to Adult Astrocytic Tumour (glioblastoma / anaplastic astrocytoma), a link supported by 2 clinical trials and 20 publications, including multiple landmark Phase 3 RCTs (e.g. the Stupp protocol) that have already made temozolomide the global standard of care for this tumour type. This is best understood as evidence confirming an established indication rather than a novel repurposing signal — the evidence pack does not record a distinct “original indication” for temozolomide, and the literature shows the predicted indication essentially overlaps with its long-standing clinical use.

Quick Overview

Item	Content
Original Indication	Not captured as structured data in this evidence pack; literature indicates temozolomide is already an established chemotherapy for glioblastoma/anaplastic astrocytoma
Predicted New Indication	Adult Astrocytic Tumour
TxGNN Prediction Score	99.36%
Evidence Level	L1
South Africa Market Status	Not marketed (unregistered)
Number of SAHPRA Registrations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Mechanism-of-action data was not returned from DrugBank for this evidence pack, but the accompanying repurposing rationale supplies the relevant pharmacology: temozolomide is an oral imidazotetrazine DNA-alkylating agent that crosses the blood–brain barrier and methylates guanine at the O6 position of DNA. Failure of DNA mismatch repair to resolve this lesion triggers apoptosis in tumour cells.

This mechanism is the pharmacological basis of the Stupp protocol — concomitant and adjuvant temozolomide with radiotherapy — which has been the global standard of care for newly diagnosed glioblastoma since the 2005 NEJM trial (PMID 15758009) and remains supported by numerous subsequent Phase 3 trials. Because “adult astrocytic tumour” (which includes glioblastoma and anaplastic astrocytoma) is precisely the tumour category temozolomide was developed and approved for elsewhere, the TxGNN signal here reflects a well-established, mechanistically direct relationship rather than an exploratory cross-indication hypothesis.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00052455	Phase 3	Completed	500	Randomised trial comparing temozolomide alone vs. 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; temozolomide used as a co-administered standard-of-care backbone, not the primary study drug

No South African National Clinical Trials Register (SANCTR) or Pan African Clinical Trials Registry (PACTR) entries were returned in this evidence pack.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
15758009	2005	RCT	N Engl J Med	Landmark Stupp trial: radiotherapy plus concomitant/adjuvant temozolomide improves survival over radiotherapy alone in glioblastoma
19269895	2009	RCT (5-year follow-up)	Lancet Oncol	EORTC-NCIC trial 5-year analysis confirms durable survival benefit of temozolomide + radiotherapy
30782343	2019	RCT (CeTeG/NOA-09)	Lancet	Lomustine-temozolomide combination superior to temozolomide alone in MGMT-methylated glioblastoma
26670971	2015	RCT	JAMA	Tumor-Treating Fields plus temozolomide improves survival vs. temozolomide alone in glioblastoma maintenance therapy
24552317	2014	RCT (AVAglio)	N Engl J Med	Bevacizumab added to temozolomide/radiotherapy in newly diagnosed glioblastoma
22578793	2012	RCT (NOA-08)	Lancet Oncol	Temozolomide alone vs. radiotherapy alone in elderly patients with malignant astrocytoma
40779733	2025	RCT (NRG Oncology BN007)	J Clin Oncol	Dual immune checkpoint blockade evaluated alongside temozolomide-based regimens in MGMT-unmethylated glioblastoma
36809318	2023	Review	JAMA	Overview of glioblastoma and other primary brain malignancies in adults, including temozolomide-based standard of care
25920709	2015	Review	J Neurooncol	Radiotherapy and temozolomide outcomes in anaplastic astrocytic gliomas
41345097	2025	Phase Ib/II trial (GEINO 1602)	Nat Commun	Glasdegib combined with temozolomide/radiotherapy in newly diagnosed glioblastoma

South Africa Market Information

Temozolomide has 0 SAHPRA registrations on record in this evidence pack and market status is not marketed. No product registration table can be generated at this time; this must be confirmed directly against the SAHPRA product register before any clinical planning proceeds.

Cytotoxicity

Temozolomide is an antineoplastic alkylating agent (imidazotetrazine class), used for a malignant tumour indication, so this section applies.

Item	Content
Cytotoxicity Classification	Conventional cytotoxic — alkylating agent (imidazotetrazine class)
Myelosuppression Risk	Please refer to the Professional Information (PI) warnings and precautions — no drug-specific toxicity data was returned in this evidence pack
Emetogenicity Classification	Please refer to the Professional Information (PI) warnings and precautions
Monitoring Items	Full blood count with differential and platelets, liver and renal function — confirm exact schedule against the PI
Handling Protection	Standard cytotoxic drug handling precautions apply; confirm against institutional protocol and the PI

Safety Considerations

Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: The mechanistic and clinical evidence for temozolomide in astrocytic tumours is exceptionally strong (L1, multiple completed Phase 3 RCTs), but the drug is currently unregistered in South Africa and the evidence pack has two data gaps: TFDA/PI-equivalent warnings and contraindications (Blocking) and confirmed mechanism-of-action documentation (High). These gaps must close before a formal safety review (S1) can proceed, even though clinical efficacy evidence is not in question.

To proceed, the following is needed:

SAHPRA-approved Professional Information (PI), including warnings, contraindications, and drug interaction data
Confirmation of DrugBank-sourced mechanism-of-action documentation
SAHPRA registration/import pathway status for temozolomide in South Africa
Clarification of the originally approved indication, since this was not captured as structured data in the evidence pack
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.