Temsirolimus
| Evidence Level: L2 | Predicted Indications: 3 |
Table of Contents
Temsirolimus: From Renal Cell Carcinoma to Liposarcoma
One-Sentence Summary
Temsirolimus is an mTOR inhibitor known internationally as an antineoplastic agent; India-specific approved-indication data is not present in this evidence pack. The TxGNN model predicts it may be effective for Liposarcoma, with 5 clinical trials and 1 publication currently supporting this direction, though only one trial uses Temsirolimus itself directly.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available in evidence pack (original_indications empty; Temsirolimus is globally recognized as an antineoplastic mTOR inhibitor) |
| Predicted New Indication | Liposarcoma |
| TxGNN Prediction Score | 99.54% (rank 7926) |
| Evidence Level | L2 |
| India Market Status | ✗ Not Marketed |
| Number of Registrations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action (MOA) data is not available in the evidence pack (flagged as a High-severity data gap, DG002). Based on the drug’s known pharmacological class, Temsirolimus is a rapalog (mTOR inhibitor) that blocks signaling through the PI3K/AKT/mTOR pathway, a pathway central to cell growth and proliferation control in oncology.
The evidence pack does not record an India-approved original indication for Temsirolimus (market status: not marketed, 0 registrations), so a direct “original vs. new indication” comparison cannot be made from local regulatory data. However, per the evidence pack’s own repurposing rationale, the PI3K/AKT/mTOR pathway is frequently dysregulated in well-differentiated and dedifferentiated liposarcoma — often downstream of MDM2/CDK4 amplification — which provides a plausible mechanistic basis for mTOR-inhibitor activity in this tumor type.
That said, direct clinical evidence using Temsirolimus itself (rather than same-class agents such as sirolimus, ridaforolimus, or everolimus) in liposarcoma is limited to a single small Phase 1/2 combination trial (NCT00949325, n=24). The majority of supporting evidence reflects a class effect across rapalogs rather than drug-specific confirmation.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00949325 | Phase 1/2 | Completed | 24 | Torisel (Temsirolimus brand name) combined with liposomal doxorubicin in advanced soft tissue/bone sarcoma, including liposarcoma; the only trial directly evidencing Temsirolimus in this disease group. |
| NCT02821507 | Phase 2 | Completed | 70 | Sirolimus (same-class rapalog) + cyclophosphamide in metastatic/unresectable myxoid liposarcoma and chondrosarcoma; disease-specific but different drug. |
| NCT00093080 | Phase 2 | Completed | 216 | AP23573 (ridaforolimus, same-class mTOR inhibitor) in advanced sarcoma; largest trial supporting rapalog activity in sarcoma. |
| NCT03114527 | Phase 2 | Active, not recruiting | 48 | Ribociclib + Everolimus (same-class) in advanced dedifferentiated liposarcoma and leiomyosarcoma. |
| NCT01614795 | Phase 2 | Completed | 46 | Cixutumumab + Temsirolimus in pediatric recurrent/refractory sarcoma; direct drug use but pediatric, non-liposarcoma-specific population. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 20497911 | 2010 | Review | Bulletin du cancer | Reviews targeted treatment approaches for rare connective tissue tumors and sarcomas, classified by molecular subgroup, including pathways relevant to mTOR-targeted therapy. |
India Market Information
Temsirolimus is not currently marketed in India. No registration records are available in this evidence pack (total_licenses: 0).
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (mTOR inhibitor / rapalog class) |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Suggested based on DDI profile: renal and hepatic function, blood glucose and lipid panel, complete blood count |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Drug Interactions: The evidence pack records 540 total interactions (ddinter source). Notable Major-level interactions include:
- Amphotericin B / Amphotericin B (lipid complex)
- Dexamethasone
- Clarithromycin
Notable Moderate-level interactions include Acarbose, Hydrocortisone, Metformin, Pioglitazone, Aprepitant, Cimetidine, Canagliflozin, Dapagliflozin, and several corticosteroids (Betamethasone, Budesonide, Triamcinolone), among others.
Key warnings and contraindications are not available in this evidence pack (flagged as Blocking data gap DG001). Please refer to the package insert for complete safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: A Blocking-severity data gap (missing India label warnings/contraindications, DG001) prevents completion of the S1 safety initial review, and evidence level is L2 with only one small Phase 1/2 trial (n=24) directly using Temsirolimus in the liposarcoma population — most supporting data reflects a rapalog class effect rather than drug-specific evidence. The drug is also not currently marketed in India.
To proceed, the following is needed:
- India-specific label warnings and contraindications (resolve DG001, Blocking)
- Confirmed mechanism of action data from DrugBank (resolve DG002)
- Larger, disease-specific clinical evidence using Temsirolimus itself in liposarcoma (beyond the single n=24 trial)
- Regulatory pathway assessment given current “not marketed” status in India
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.