Temozolomide

證據等級: L5

預測適應症: 2 個

Temozolomide: From Glioblastoma to Adult Astrocytic Tumour

One-Sentence Summary

Temozolomide is an oral alkylating chemotherapy agent whose established clinical use — based on the literature captured in this evidence pack — is the treatment of glioblastoma and other high-grade gliomas. The TxGNN model predicts it may be effective for Adult Astrocytic Tumour, with 2 clinical trials and 20 publications currently supporting this direction — though much of this evidence describes temozolomide's already-established standard-of-care role rather than a novel repurposing signal (see rationale below).

Quick Overview

Item	Content
Original Indication	Not provided in structured regulatory data; literature within this evidence pack consistently identifies glioblastoma/malignant glioma as the drug's established use (see Why is This Prediction Reasonable?)
Predicted New Indication	Adult astrocytic tumour
TxGNN Prediction Score	99.36%
Evidence Level	L1 (≥2 completed Phase 3 RCTs — e.g. NCT00052455, plus Stupp 2005/2009, Wick 2012, Herrlinger 2019, Stupp 2015)
Norway Market Status	Not marketed
Number of Authorizations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism-of-action data is not available in this evidence pack (flagged as data gap DG002, High severity). Based on the literature attached to this candidate, temozolomide is an oral imidazotetrazine alkylating agent that induces DNA methylation-mediated cytotoxicity in tumour cells; it is described repeatedly across the retrieved publications as the backbone of chemoradiotherapy for glioblastoma (the Stupp protocol, NEJM 2005).

Glioblastoma is itself a high-grade astrocytic tumour, so the top-ranked TxGNN prediction ("adult astrocytic tumour") largely overlaps with the drug's already-documented use rather than representing a mechanistically distant new indication. The very high TxGNN score (99.36%) and the depth of Phase 3 evidence are therefore consistent with confirming an existing therapeutic relationship, not discovering a new one. This should be explicitly noted to decision-makers: the value of this candidate lies in confirming/documenting an established indication rather than in genuine repurposing novelty.

By contrast, the second-ranked prediction in this pack — cauda equina neoplasm (spinal myxopapillary ependymoma) — is mechanistically more novel and is supported only by a single case report (PMID 29270703) describing remarkable efficacy in a relapsed, disseminated case. This is a much earlier-stage signal that may warrant separate tracking.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00960492	Phase 1	Completed	26	Dose-finding study of XL184 (cabozantinib) combined with temozolomide and radiation in first-line glioblastoma
NCT00052455	Phase 3	Completed	500	Randomized comparison of temozolomide vs. PCV regimen in recurrent WHO Grade III/IV astrocytic tumours

Literature Evidence

PMID	Year	Type	Journal	Key Findings
15758009	2005	RCT (Phase 3)	N Engl J Med	Landmark Stupp trial: radiotherapy + concomitant/adjuvant temozolomide vs. radiotherapy alone for newly diagnosed glioblastoma
19269895	2009	RCT (Phase 3, 5-yr follow-up)	Lancet Oncol	Confirms sustained survival benefit of temozolomide + radiotherapy in glioblastoma (EORTC-NCIC trial)
22578793	2012	RCT (Phase 3)	Lancet Oncol	NOA-08 trial: temozolomide alone vs. radiotherapy alone in elderly patients with malignant astrocytoma
24552317	2014	RCT (Phase 3)	N Engl J Med	Bevacizumab added to standard temozolomide/radiotherapy in newly diagnosed glioblastoma
26670971	2015	RCT (Phase 3)	JAMA	Tumor-Treating Fields + temozolomide vs. temozolomide alone as maintenance therapy in glioblastoma
30782343	2019	RCT (Phase 3)	Lancet	CeTeG/NOA-09: lomustine-temozolomide combination vs. standard temozolomide in MGMT-methylated glioblastoma
41345097	2025	Trial (Phase Ib/II)	Nat Commun	GEINO 1602: glasdegib + temozolomide/radiotherapy in newly diagnosed glioblastoma
38768767	2024	Trial (Phase 1/2)	Int J Radiat Oncol Biol Phys	Disulfiram/copper combined with radiotherapy and temozolomide in newly diagnosed glioblastoma
36809318	2023	Review	JAMA	Review of glioblastoma and other primary adult brain malignancies
29075865	2017	Review	Curr Oncol Rep	Review of glioblastoma treatment approaches in older adults

Norway Market Information

Temozolomide is not currently marketed in this jurisdiction (market_status: 未上市), and no authorizations are on record (total_licenses: 0). No product/license table can be produced from available data.

Cytotoxicity

Temozolomide is an alkylating chemotherapy agent, meeting the antineoplastic classification criteria (cytotoxic drug class; established use in malignant glioma per literature above).

Item	Content
Cytotoxicity Classification	Conventional cytotoxic (alkylating agent, imidazotetrazine class)
Myelosuppression Risk	High — alkylating agents in this class are typically associated with dose-limiting thrombocytopenia and neutropenia; drug-specific toxicity grading data is not available in this pack (see DG001)
Emetogenicity Classification	Moderate (typical for oral alkylating agents in this class)
Monitoring Items	CBC with differential (baseline and periodic during treatment), liver function tests, renal function
Handling Protection	Cytotoxic drug handling precautions apply (capsule should not be opened/crushed; standard hazardous drug handling protocols recommended)

Note: the above reflects general characteristics of this drug class. Drug-specific toxicity data (package insert) is a blocking data gap (DG001) and should be confirmed before clinical use.

Safety Considerations

Please refer to the package insert for safety information. Key warnings, contraindications, and drug interaction data are currently unavailable in this evidence pack (flagged as DG001, Blocking severity — this specifically prevents completion of the S1 preliminary safety assessment).

Conclusion and Next Steps

Decision: Hold

Rationale: Efficacy evidence for temozolomide in astrocytic tumours is very strong (multiple completed Phase 3 RCTs), but this largely confirms an already-established indication rather than a novel repurposing opportunity. More importantly, a Blocking data gap (DG001) prevents completion of the mandatory S1 safety evaluation, and the drug currently has zero market authorizations in this jurisdiction.

To proceed, the following is needed:

TFDA/regulatory package insert with warnings, contraindications, and DDI data (resolves DG001 — required before S1 safety evaluation can proceed)
DrugBank-sourced mechanism-of-action detail (resolves DG002)
Clarification of true repurposing novelty for "adult astrocytic tumour," given substantial overlap with temozolomide's established glioblastoma use
If pursued: confirmation of regulatory pathway/authorization plans, since the drug is not currently marketed
Secondary signal for future tracking: cauda equina neoplasm (spinal myxopapillary ependymoma) is supported only by a single case report (PMID 29270703) and requires substantially more evidence (preclinical or prospective clinical data) before advancing
Disclaimer

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