Temsirolimus

證據等級: L5

預測適應症: 3 個

Temsirolimus: From mTOR-Targeted Oncology Therapy to Liposarcoma

One-Sentence Summary

Temsirolimus is an mTOR inhibitor (a prodrug of sirolimus) used in oncology; its specific original approved indication is not recorded in this evidence pack. The TxGNN model predicts it may be effective for Liposarcoma, with 5 clinical trials (2 using temsirolimus directly, Grade A) and 1 publication currently supporting this direction.

Quick Overview

Item	Content
Original Indication	Not available in evidence pack (no approved indication text on file; drug not marketed in Norway)
Predicted New Indication	Liposarcoma
TxGNN Prediction Score	99.54%
Evidence Level	L3
Norway Market Status	✗ Not Marketed
Number of Authorizations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism-of-action data for temsirolimus is not available in this evidence pack. Based on the drug repurposing rationale provided, temsirolimus is an mTOR inhibitor (prodrug of sirolimus) that blocks the PI3K/AKT/mTOR signaling pathway. This pathway is a well-established target in oncology, and the evidence pack notes it is frequently dysregulated in dedifferentiated and myxoid liposarcoma subtypes (e.g., through CDK4/MDM2 amplification-driven downstream signaling or PTEN loss).

The relationship between temsirolimus's original use and liposarcoma is mechanistic rather than indication-based, since no original approved indication is recorded here. However, two of the five identified clinical trials used temsirolimus itself (brand name Torisel) directly in sarcoma populations — one in combination with liposomal doxorubicin, and one in pediatric recurrent/refractory sarcoma with cixutumumab — both rated Grade A relevance by the evidence pipeline.

The remaining three trials use related mTOR pathway inhibitors (sirolimus, ridaforolimus, everolimus) rather than temsirolimus itself, providing class-level rather than drug-specific support. Historically, single-agent mTOR inhibition has shown only limited, non-definitive efficacy in liposarcoma trials, suggesting that combination regimens (with cytotoxic chemotherapy or IGF-1R inhibitors) are more likely to be clinically meaningful than monotherapy.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00949325	Phase 1/2	Completed	24	Torisel (temsirolimus) + liposomal doxorubicin in recurrent soft tissue/bone sarcoma; dose-finding and efficacy assessment. Direct drug evidence.
NCT01614795	Phase 2	Completed	46	Temsirolimus + cixutumumab (IMC-A12) in pediatric recurrent/refractory sarcoma. Direct drug evidence.
NCT02821507	Phase 2	Completed	70	Sirolimus + cyclophosphamide in metastatic/unresectable myxoid liposarcoma and chondrosarcoma. Class-effect (sirolimus, not temsirolimus).
NCT00093080	Phase 2	Completed	216	Ridaforolimus (AP23573), an mTOR inhibitor, in advanced sarcoma. Class-effect evidence, largest cohort.
NCT03114527	Phase 2	Active, not recruiting	48	Ribociclib + everolimus in advanced dedifferentiated liposarcoma and leiomyosarcoma. Class-effect (everolimus, not temsirolimus).

Literature Evidence

PMID	Year	Type	Journal	Key Findings
20497911	2010	Review	Bulletin du cancer	Review of targeted treatments for rare connective tissue tumors and sarcomas, covering molecular subtyping and pathway-directed therapy approaches.

Norway Market Information

Temsirolimus currently holds no marketing authorization in Norway (0 authorizations on file); no product or dosage form data is available.

Cytotoxicity

Item	Content
Cytotoxicity Classification	Targeted therapy (mTOR inhibitor)
Myelosuppression Risk	Please refer to the package insert warnings and precautions
Emetogenicity Classification	Please refer to the package insert warnings and precautions
Monitoring Items	Please refer to the package insert warnings and precautions
Handling Protection	Please refer to the package insert warnings and precautions

Safety Considerations

Please refer to the package insert for safety information. Note: TFDA-equivalent labeling data (warnings/contraindications) for this drug is currently a blocking data gap, which prevents completion of the standard S1 safety pre-assessment.

Conclusion and Next Steps

Decision: Hold

Rationale: While two trials use temsirolimus directly in sarcoma populations (Grade A relevance) and the mTOR pathway has a plausible mechanistic role in liposarcoma, the evidence is limited to Phase 1/2 studies with no confirmatory Phase 3 data, and the drug is not marketed in Norway. Critically, the missing TFDA-equivalent labeling data is a blocking gap that prevents a safety pre-assessment (S1), so the candidate cannot yet advance to Go or Proceed with Guardrails.

To proceed, the following is needed:

TFDA (or equivalent) label warnings/contraindications, to unblock the S1 safety assessment (DG001)
Confirmed mechanism-of-action and DrugBank category/toxicity data (DG002)
Original approved indication(s) for temsirolimus, to properly frame the repurposing rationale
Additional liposarcoma-specific trial data, ideally combination-regimen Phase 2/3 results, given monotherapy's historically limited efficacy in this tumor type
Route-of-administration compatibility assessment (currently pending)
Disclaimer

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