Temsirolimus

證據等級: L5

預測適應症: 6 個

Temsirolimus: From Renal Cell Carcinoma to Liposarcoma

One-Sentence Summary

Temsirolimus is an mTOR inhibitor originally approved for renal cell carcinoma. The TxGNN model predicts it may also be effective for Liposarcoma, with 5 clinical trials (including two using temsirolimus itself) and 1 publication currently supporting this direction.

Quick Overview

Item	Content
Original Indication	Renal cell carcinoma (per repurposing rationale; no Danish licence record available)
Predicted New Indication	Liposarcoma
TxGNN Prediction Score	99.54%
Evidence Level	L2
Denmark Market Status	Not marketed
Number of Marketing Authorisations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed original mechanism-of-action documentation is not yet available in this evidence pack (flagged as a data gap). However, the repurposing rationale confirms temsirolimus is an mTOR inhibitor and a pro-drug of sirolimus, currently approved for renal cell carcinoma.

Dedifferentiated and myxoid subtypes of liposarcoma are frequently driven by PI3K/AKT/mTOR pathway activation together with MDM2/CDK4 co-amplification, producing a well-established mechanistic rationale for mTOR inhibition in this tumour type. Since liposarcoma has no approved link to the original renal cell carcinoma indication, this use would remain off-label and exploratory.

This mechanistic plausibility is reinforced by clinical experience with mTOR-pathway drugs (sirolimus, ridaforolimus, everolimus) across various sarcoma subtypes, and by two trials using temsirolimus itself directly in sarcoma populations — supporting the biological reasonableness of the TxGNN prediction, though direct pivotal evidence in liposarcoma specifically is still limited.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT01614795	Phase 2	Completed	46	Temsirolimus + cixutumumab in pediatric recurrent/refractory sarcoma; direct temsirolimus evidence
NCT00093080	Phase 2	Completed	216	Ridaforolimus (mTOR inhibitor class analog, not temsirolimus) in advanced sarcoma
NCT02821507	Phase 2	Completed	70	Sirolimus (active metabolite of temsirolimus) + cyclophosphamide in metastatic/unresectable myxoid liposarcoma and chondrosarcoma
NCT03114527	Phase 2	Active, not recruiting	48	Everolimus (mTOR inhibitor class analog) + ribociclib in dedifferentiated liposarcoma and leiomyosarcoma
NCT00949325	Phase 1/2	Completed	24	Torisel (temsirolimus) + liposomal doxorubicin in advanced soft tissue/bone sarcoma; direct temsirolimus evidence

Literature Evidence

PMID	Year	Type	Journal	Key Findings
20497911	2010	Review	Bulletin du cancer	Reviews targeted treatment approaches for rare connective tissue tumours and sarcomas by molecular subgroup

Denmark Market Information

Temsirolimus currently has no marketing authorisation on record in Denmark (0 authorisations; market status: not marketed).

Cytotoxicity

Item	Content
Cytotoxicity Classification	Targeted therapy (mTOR inhibitor / kinase inhibitor class)
Myelosuppression Risk	Please refer to the Summary of Product Characteristics (SmPC) — no toxicity data available in this evidence pack
Emetogenicity Classification	Please refer to the Summary of Product Characteristics (SmPC) — no toxicity data available in this evidence pack
Monitoring Items	Please refer to the Summary of Product Characteristics (SmPC) — no toxicity data available in this evidence pack
Handling Protection	Please refer to the Summary of Product Characteristics (SmPC) — no toxicity data available in this evidence pack

Safety Considerations

Please refer to the approved Summary of Product Characteristics (SmPC) for safety information.

Conclusion and Next Steps

Decision: Hold

Rationale: Temsirolimus is not currently marketed in Denmark, and the underlying safety documentation (warnings, contraindications) needed for initial safety screening is entirely missing — a blocking data gap. While mechanistic and Phase 1/2 evidence in sarcoma is encouraging, direct pivotal evidence for temsirolimus specifically in liposarcoma remains at the research-question stage.

To proceed, the following is needed:

TFDA/SmPC label data on warnings and contraindications (blocking gap)
Confirmed detailed mechanism-of-action documentation from DrugBank
A dedicated liposarcoma trial evaluating temsirolimus monotherapy or combination regimens, rather than relying solely on class-effect evidence from related mTOR inhibitors
Disclaimer

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