Temsirolimus

Evidence Level: L5

Predicted Indications: 3

Temsirolimus

Pharmacist Assessment Report

Temsirolimus: Liposarcoma

One-Sentence Summary

Temsirolimus is an mTOR inhibitor originally used to treat renal cell carcinoma and mantle cell lymphoma. The TxGNN model predicts it may be effective for liposarcoma, with 2 clinical trials (both in sarcoma populations, not liposarcoma-specific) and 1 publication currently supporting this direction.

Quick Overview

Item	Content
Original Indication	Not recorded in the local data
Predicted New Indication	Liposarcoma
TxGNN Prediction Score	0.9954
Evidence Level	L5
India Market Status	Listed in a compiled Indian medicine price dataset (2 of 2) – CDSCO approval status is not included in this data
Number of Listed Products	2 (valid: 2)
Recommended Decision	Hold (research question; further evidence needed)

Why is This Prediction Reasonable?

Detailed mechanism of action data is not available in the data compiled for this report. Based on the pathway analysis, temsirolimus inhibits mTOR (through the FKBP12 complex), a node downstream of PI3K/AKT signalling. Its efficacy in renal cell carcinoma and mantle cell lymphoma is established, and mechanistically it may be applicable to liposarcoma.

Activation of the mTOR pathway and of IGF-1R/PI3K signalling has been implicated in sarcoma growth, including liposarcoma. Blocking IGF-1R together with mTOR (as with cixutumumab plus temsirolimus) targets the compensatory feedback activation of AKT. Combining temsirolimus with a liposarcoma-active cytotoxic such as liposomal doxorubicin is also plausible.

The high TxGNN score is consistent with this pathway rationale, but it remains a computational prediction. Two other predicted indications, ovarian myxoid liposarcoma (0.9947) and vulva sarcoma (0.9909), have no supporting trials or literature and are likely extrapolations from the same sarcoma-pathway signal.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00949325	Phase 1/2	Completed	24	Temsirolimus (Torisel) plus liposomal doxorubicin in recurrent advanced soft tissue and bone sarcomas; aims to identify a safe dose and assess effectiveness. Population is mixed, and liposarcoma-specific results are not confirmed.
NCT01614795	Phase 2	Completed	46	Cixutumumab plus temsirolimus in pediatric patients with recurrent or refractory solid tumours including sarcoma. Limited direct relevance to adult liposarcoma; supports the mTOR/IGF-1R combination rationale only.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
20497911	2010	Review	Bulletin du cancer	Review of targeted treatments for rare connective tissue tumours and sarcomas, organised by molecular subgroup. The abstract excerpt available does not describe temsirolimus-specific findings.

India Market Information

Authorization Number	Product Name	Dosage Form	Approved Indication
Registration No. 210129	Sirotem Injection (Celon Laboratories Ltd)	Vial of 1 ml injection	Not stated in the licence record
Registration No. 222031	Torisel Kit (Pfizer Ltd)	Vial of 1 ml injection	Not stated in the licence record

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
Handling Protection	Please refer to the package insert warnings and precautions; follow institutional antineoplastic handling policy

Safety Considerations

Drug Interactions: 540 interactions were identified in the interaction databases. Examples of those rated Major: amphotericin B (including the lipid complex), dexamethasone, and clarithromycin. Examples rated Moderate include hydrocortisone, other corticosteroids (triamcinolone, betamethasone, budesonide), aprepitant, cimetidine, mesalazine, balsalazide, and several antidiabetic drugs (acarbose, metformin, pioglitazone, alogliptin, albiglutide, canagliflozin, dapagliflozin, chlorpropamide).
Knowledge-graph contraindication signals (from the TxGNN knowledge graph, not from label text, so they should be verified against the package insert):
- Metabolic: hyperglycaemia, diabetes mellitus, diabetic ketoacidosis, hyperlipidaemia (including familial)
- Organ function: kidney disease, liver disease, gallbladder disease, hyperbilirubinaemia (including Gilbert syndrome), interstitial lung disease
- Cerebrovascular: stroke, cerebrovascular disorder, cerebral infarction
- Central nervous system tumours: brain cancer and several astrocytoma, glioblastoma and oligodendroglial tumour types

Package insert warnings and contraindications were not available for this report; please refer to the package insert.

Conclusion and Next Steps

Decision: Hold

Rationale: Temsirolimus has a plausible mTOR/PI3K pathway rationale for liposarcoma and a very high model score. However, the only supporting trials are a small mixed-sarcoma Phase 1/2 study and a paediatric Phase 2 study, with no liposarcoma-specific efficacy data and no confirmatory trials. The package insert safety review is also incomplete, so the case is best treated as a research question rather than a candidate for advancement.

To proceed, the following is needed:

Liposarcoma-specific results (subgroup data) from NCT00949325 and related sarcoma studies
Package insert warnings and contraindications from the India licence holders, to complete safety screening
Detailed mechanism of action data
A review of the knowledge-graph contraindication signals (metabolic, hepatic, pulmonary, cerebrovascular) against label text, and a drug-interaction management plan (especially with dexamethasone, clarithromycin, and amphotericin B)
Preclinical or translational evidence of mTOR pathway dependence in liposarcoma subtypes
Disclaimer

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