Temsirolimus

證據等級: L5

預測適應症: 3 個

Temsirolimus: From Renal Cell Carcinoma to Liposarcoma

One-Sentence Summary

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

Quick Overview

Item	Content
Original Indication	Renal cell carcinoma (per repurposing rationale; no local license record — see Market Status)
Predicted New Indication	Liposarcoma
TxGNN Prediction Score	99.54%
Evidence Level	L2
Finland Market Status	✗ Not Marketed
Number of Authorizations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

The original_moa field for temsirolimus is flagged as a data gap in this evidence pack (DG002 — High severity). However, the repurposing rationale attached to the prediction supplies mechanistic detail: temsirolimus is a prodrug of sirolimus, and after CYP3A4-mediated metabolic activation it binds FKBP12 to inhibit mTORC1, blocking the PI3K/AKT/mTOR signaling pathway.

Liposarcoma — particularly the dedifferentiated subtype — frequently shows activation of this same pathway along with MDM2/CDK4 co-amplification, giving a clear mechanistic rationale for extending temsirolimus beyond its approved indication of renal cell carcinoma, another tumor type driven by mTOR pathway dysregulation.

This mechanistic continuity is reinforced by direct clinical evidence: temsirolimus itself (as Torisel) has already been tested in combination regimens for advanced soft-tissue and bone sarcomas, including liposarcoma subtypes, and other mTOR-pathway inhibitors (sirolimus, ridaforolimus, everolimus) have been studied in the same disease space, forming a broader class-level evidence base.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00949325	Phase 1/2	Completed	24	Torisel (temsirolimus) + liposomal doxorubicin in recurrent sarcoma (incl. liposarcoma); dose-finding and efficacy assessment. Direct evidence for temsirolimus.
NCT01614795	Phase 2	Completed	46	Temsirolimus + cixutumumab in pediatric recurrent/refractory sarcoma. Direct evidence for temsirolimus, but population limited to pediatrics.
NCT02821507	Phase 2	Completed	70	Sirolimus + cyclophosphamide in metastatic/unresectable myxoid liposarcoma and chondrosarcoma. Same-class (mTOR inhibitor) evidence.
NCT00093080	Phase 2	Completed	216	Ridaforolimus (another mTOR inhibitor) in advanced sarcoma; large sample size, same-class evidence.
NCT03114527	Phase 2	Active, not recruiting	48	Ribociclib + everolimus (mTOR inhibitor) in advanced dedifferentiated liposarcoma and leiomyosarcoma. Same-class evidence, ongoing.

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, classifying molecular subgroups relevant to targeted therapy selection.

Finland Market Information

Temsirolimus is not currently marketed in Finland — 0 authorizations are on record in this evidence pack.

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. (Local package insert warnings/contraindications and DDI data are not yet available — flagged as a Blocking data gap, DG001.)

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Temsirolimus itself has completed Phase 1/2 clinical evidence in sarcoma (including liposarcoma), reinforced by a coherent mTOR-pathway mechanistic rationale and supportive same-class trial data. However, the drug is not currently marketed in Finland and key safety/regulatory data are missing, so guardrails are needed before advancing further.

To proceed, the following is needed:

TFDA/local package insert warnings and contraindications (Blocking gap, DG001)
Detailed mechanism of action documentation from DrugBank (High-priority gap, DG002)
Local market authorization or import pathway assessment, since the product is not currently marketed
Drug-drug interaction data (none found in current query)
Disclaimer

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