Sirolimus
| Evidence Level: L5 | Predicted Indications: 6 |
Table of Contents
Sirolimus: Liposarcoma
One-Sentence Summary
Sirolimus is an mTOR inhibitor that is currently marketed in India under 15 valid licences. The TxGNN model predicts it may be useful for liposarcoma. Only 1 completed single-arm Phase 2 trial (a sirolimus combination) is linked, and it has no posted results. No published study directly tests sirolimus in liposarcoma, so the evidence is classed as model prediction only.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Liposarcoma |
| TxGNN Prediction Score | 0.9989 |
| Evidence Level | L5 |
| India Market Status | Listed in a compiled Indian medicine price dataset (15 of 15) – CDSCO approval status is not included in this data |
| Number of Listed Products | 15 (valid: 15) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data for sirolimus are not available in the data compiled for this report. Sirolimus is known to inhibit mTORC1. Activation of the PI3K/AKT/mTOR pathway has been reported in soft tissue sarcomas, including liposarcoma. Blocking mTORC1 could therefore slow tumour growth.
This is a mechanistic hypothesis only. The linked trial tests sirolimus in combination with another drug, so sirolimus’s own contribution cannot be separated. The sarcoma literature is limited to reviews. Transplant data showing lower cancer risk under sirolimus are indirect and do not show activity against liposarcoma.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02821507 | Phase 2 | Completed | 70 | Single-arm, multicentre trial of sirolimus plus cyclophosphamide in metastatic or unresectable myxoid liposarcoma and chondrosarcoma. It was motivated by preclinical data suggesting mTOR inhibition can prevent tumour growth. No results are published or posted, and the combination design cannot isolate sirolimus’s effect. |
Literature Evidence
None of these publications reports a test of sirolimus in liposarcoma. They are background or indirect evidence.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 16434506 | 2006 | RCT (indirect) | J Am Soc Nephrol | In renal transplant recipients, switching to sirolimus after early cyclosporine withdrawal reduced the risk of cancer. This is a transplant outcome, not liposarcoma treatment. |
| 39796641 | 2024 | Review | Cancers | Overview of novel therapeutics in soft tissue sarcoma. |
| 37222206 | 2023 | Review | Curr Opin Oncol | Rationale and results of recent trials of molecular-targeted agents in advanced sarcomas. |
| 20497911 | 2010 | Review | Bull Cancer | Targeted treatments for molecular subgroups of rare connective tissue tumours and sarcomas. |
| 26093731 | 2015 | Review | Transplant Proc | Cancer screening in renal transplant patients on long-term immunosuppression (indirect). |
India Market Information
Sirolimus has 15 valid licences, all for single-ingredient products. The approved-indication text is not recorded in the local data. Five of the licences are listed below.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 185868 | Rapamune 1mg Tablet (Pfizer Ltd) | Strip of 10 tablets | Not stated |
| 191166 | Raparen 1mg Injection (La Renon Healthcare) | Vial of 1 injection | Not stated |
| 190480 | Rapacan 2mg Capsule (Biocon) | Strip of 10 capsules | Not stated |
| 200266 | Siromus 1mg Tablet (Zydus Cadila) | Strip of 6 tablets | Not stated |
| 222768 | Toraft 1mg Tablet (Torrent) | Strip of 10 tablets | Not stated |
Safety Considerations
- Drug Interactions: 645 interactions are recorded. Examples classed as Major include amphotericin B (including the lipid complex), mesalazine, balsalazide and clarithromycin. Moderate examples include several corticosteroids (hydrocortisone, dexamethasone, betamethasone, budesonide, triamcinolone), antidiabetic agents (metformin, pioglitazone, acarbose, alogliptin, canagliflozin, dapagliflozin), cimetidine and aprepitant.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The only supporting study is an unpublished single-arm Phase 2 combination trial. No published study tests sirolimus in liposarcoma, and the remaining literature is indirect. The high model score and the plausible mTOR rationale justify further research, not a decision to advance.
To proceed, the following is needed:
- Results of NCT02821507, with the liposarcoma subgroup and the contribution of sirolimus separated from cyclophosphamide
- Published clinical studies of sirolimus in liposarcoma
- Detailed mechanism-of-action data
- Package insert warnings and contraindications for the marketed products
- A plan to manage the large number of drug interactions
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.