Temsirolimus

證據等級: L5

預測適應症: 3 個

Temsirolimus: From Unspecified Oncology Indication to Liposarcoma

One-Sentence Summary

Temsirolimus (DrugBank ID: DB06287) is an mTOR inhibitor (rapalog); however, its originally approved indication is not documented in the current evidence pack, and the drug is currently not marketed in Germany. The TxGNN model predicts it may be effective for Liposarcoma, supported by 5 clinical trials (2 using temsirolimus directly) and 1 publication currently on record.

Quick Overview

Item	Content
Original Indication	Not documented in current dataset (no German license/indication text available)
Predicted New Indication	Liposarcoma
TxGNN Prediction Score	99.54%
Evidence Level	L2
Germany Market Status	✗ Not marketed
Number of Authorizations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available (flagged as a High-severity data gap, pending DrugBank/TFDA verification). Based on the information available in this evidence pack, temsirolimus is an mTOR inhibitor (rapalog). Liposarcoma — particularly the dedifferentiated and myxoid subtypes — frequently shows PI3K/AKT/mTOR pathway activation, and its downstream MDM2/CDK4 amplification signaling is often mTOR-dependent, providing a plausible mechanistic basis for repurposing.

Since the original approved indication of temsirolimus is not documented in this dataset, a direct disease-to-disease relationship cannot be established. However, same-class agents (sirolimus, ridaforolimus, everolimus) have already accumulated multiple completed Phase 2 trials in sarcoma populations, supporting a class-effect rationale for mTOR inhibition in this tumor type. Two of the listed trials use temsirolimus itself directly in sarcoma populations, strengthening the plausibility beyond class effect alone.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT02821507	Phase 2	Completed	70	Combination of sirolimus (mTOR inhibitor, class-related) and cyclophosphamide in metastatic/unresectable myxoid liposarcoma and chondrosarcoma
NCT00093080	Phase 2	Completed	216	Ridaforolimus (mTOR inhibitor, class-related), an mTOR inhibitor structurally distinct from temsirolimus, tested in advanced sarcoma
NCT01614795	Phase 2	Completed	46	Temsirolimus combined with cixutumumab in pediatric patients with recurrent/refractory sarcoma — direct temsirolimus evidence
NCT03114527	Phase 2	Active, not recruiting	48	Ribociclib plus everolimus (mTOR inhibitor, class-related) in advanced dedifferentiated liposarcoma and leiomyosarcoma
NCT00949325	Phase 1/2	Completed	24	Torisel (temsirolimus) plus liposomal doxorubicin in advanced soft tissue and bone sarcoma — direct temsirolimus evidence

Literature Evidence

PMID	Year	Type	Journal	Key Findings
20497911	2010	Review	Bulletin du cancer	Reviews targeted treatment strategies for rare connective tissue tumors and sarcomas, classifying molecular subgroups relevant to targeted therapy selection

Germany Market Information

Temsirolimus is currently not marketed in Germany; no authorization or licensing records are available in this dataset.

Cytotoxicity

Item	Content
Cytotoxicity Classification	Targeted therapy (mTOR inhibitor / rapalog)
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.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Two completed trials use temsirolimus directly in sarcoma populations (one Phase 2 pediatric trial, n=46; one Phase 1/2 trial, n=24), reaching Evidence Level L2, while additional Phase 2 trials support a broader mTOR-inhibitor class effect. However, the original indication, mechanism of action, and safety/label data are not yet documented in this dataset, so the recommendation cannot advance to an unconditional "Go."

To proceed, the following is needed:

TFDA/BfArM label warnings and contraindications (currently a Blocking data gap)
Confirmed mechanism of action documentation from DrugBank (currently a High-severity data gap)
Verification of the drug's original approved indication (not documented; drug not currently marketed in Germany)
Larger-scale, temsirolimus-specific (not class-effect) Phase 2/3 trials in liposarcoma to strengthen direct evidence
Disclaimer

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