Sorafenib

證據等級: L5

預測適應症: 10 個

Sorafenib: From Renal Cell Carcinoma to Liposarcoma

One-Sentence Summary

Sorafenib is a multi-target tyrosine kinase inhibitor originally developed for advanced renal cell carcinoma, later expanded to hepatocellular carcinoma and differentiated thyroid cancer. The TxGNN model predicts it may be effective for Liposarcoma, currently supported by 2 clinical trials (1 directly using sorafenib) and 8 publications, most of which are preclinical or review-level evidence.

Quick Overview

Item	Content
Original Indication	Renal cell carcinoma / hepatocellular carcinoma (based on drug's known regulatory history; not present in current dataset)
Predicted New Indication	Liposarcoma
TxGNN Prediction Score	99.82%
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 in this dataset. Based on known information, sorafenib is a multi-target tyrosine kinase inhibitor that blocks RAF/MEK/ERK signaling as well as VEGFR-1/2/3, PDGFR-β, c-KIT, and FLT3. Its efficacy in renal cell carcinoma and hepatocellular carcinoma is well established.

Liposarcoma, particularly the dedifferentiated subtype, has been shown to exhibit PTEN down-regulation and PDGFR pathway activation — both of which overlap with sorafenib's known targets. This provides a plausible mechanistic rationale for repurposing.

However, soft tissue sarcomas are highly heterogeneous, and not all subtypes respond uniformly to VEGFR/PDGFR-targeted therapy. The strongest direct clinical evidence comes from the SWOG S0505 trial, a Phase 2 study of sorafenib in advanced soft tissue sarcomas (not liposarcoma-specific), which supports biological activity but does not confirm subtype-specific efficacy.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00217620	Phase 2	Completed	51	Sorafenib (BAY 43-9006) in advanced soft tissue sarcomas, including liposarcoma subtypes; direct sorafenib evidence, corresponds to S0505 publication (PMID 21751200)
NCT02048371	Phase 2	Completed	131	SARC024 protocol testing regorafenib (not sorafenib) in selected sarcoma subtypes; included as indirect class-effect evidence only

Literature Evidence

PMID	Year	Type	Journal	Key Findings
21751200	2012	Phase 2 Trial (SWOG S0505)	Cancer	Sorafenib evaluated in advanced soft tissue sarcomas; multitargeted TKI activity against RAF, VEGFR1-3, PDGFR-β, FLT3, c-KIT
24554062	2014	Phase 1 Trial	Annals of Surgical Oncology	Neoadjuvant sorafenib + radiotherapy in extremity soft tissue sarcoma; synergistic antiangiogenic effect explored
22987955	2012	Review	Annals of Oncology	Histology-driven sarcoma therapy; trabectedin highly active in myxoid liposarcoma, context for targeted agents
24712007	2014	Review	Magyar Onkologia	Histological subtype-based medical treatment of soft tissue sarcomas
36003796	2022	Review	Frontiers in Oncology	PDOX models identify CDK inhibitor combinations for sarcoma; broader targeted therapy rationale
23416162	2013	Preclinical (PDX)	American Journal of Pathology	Dedifferentiated liposarcoma xenograft models show PTEN down-regulation as malignant signature, sensitive to PI3K pathway inhibition
18413802	2008	Preclinical	Molecular Cancer Therapeutics	Sorafenib inhibits growth and MAPK signaling in malignant peripheral nerve sheath and dedifferentiated liposarcoma cell lines
25075796	2014	Case Report (trabectedin, non-sorafenib)	Anti-Cancer Drugs	Response to trabectedin (not sorafenib) in synovial sarcoma; included for sarcoma treatment context only

Germany Market Information

Sorafenib is currently not marketed in Germany per this dataset, with no authorization records available (0 licenses on file).

Cytotoxicity

Item	Content
Cytotoxicity Classification	Targeted therapy (multi-target tyrosine kinase inhibitor; not a conventional cytotoxic agent)
Myelosuppression Risk	Low to Moderate — TKI-class drugs typically cause less myelosuppression than conventional cytotoxics; skin toxicity (hand-foot skin reaction) is a more prominent class effect
Emetogenicity Classification	Low — oral TKIs generally carry minimal emetogenic potential
Monitoring Items	Blood pressure, liver function tests, CBC, skin/dermatologic assessment, thyroid function
Handling Protection	As an oral antineoplastic agent, standard institutional hazardous-drug handling precautions apply; please refer to the package insert warnings and precautions for detailed guidance

Safety Considerations

Please refer to the package insert for safety information.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: A completed Phase 2 trial directly using sorafenib (SWOG S0505) demonstrates biological activity in advanced soft tissue sarcomas, and the PDGFR/PTEN pathway rationale for dedifferentiated liposarcoma is mechanistically plausible. However, evidence is limited to a single Phase 2 study without liposarcoma-subtype stratification, and one of the two listed trials (SARC024) actually tested regorafenib rather than sorafenib.

To proceed, the following is needed:

Resolve Blocking data gap DG001: obtain TFDA/BfArM package insert warnings and contraindications before any S1 safety review
Resolve High-priority data gap DG002: confirm detailed MOA via DrugBank API query
Liposarcoma subtype-specific clinical data (dedifferentiated vs. myxoid vs. pleomorphic), as current trial evidence is not subtype-stratified
Comparative efficacy data versus current standard-of-care agents (trabectedin, eribulin) in liposarcoma
Disclaimer

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