Sorafenib

證據等級: L5

預測適應症: 10 個

Sorafenib: From Renal Cell/Hepatocellular Carcinoma to Liposarcoma

One-Sentence Summary

Sorafenib is a multi-targeted kinase inhibitor originally established for renal cell carcinoma and hepatocellular carcinoma. The TxGNN model predicts it may also be effective for Liposarcoma, with 2 clinical trials and 8 publications currently supporting this direction.

Quick Overview

Item	Content
Original Indication	Not recorded in the Norway licensing database (sorafenib is currently not marketed there); evidence within this pack (clinical trial and literature text) identifies its established indications as hepatocellular carcinoma and renal cell carcinoma
Predicted New Indication	Liposarcoma
TxGNN Prediction Score	99.82%
Evidence Level	L2
Norway Market Status	✗ Not Marketed
Number of Authorizations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Detailed mechanism-of-action data from DrugBank is not available for this drug (data gap). Based on descriptions embedded in the clinical trial evidence within this pack, sorafenib is a multi-targeted kinase inhibitor that blocks RAF/MEK/ERK signal transduction and inhibits VEGFR-1/2/3 and PDGFR-mediated angiogenesis ("Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor" — NCT00217620). This dual anti-proliferative/anti-angiogenic mechanism underlies its established use in renal cell carcinoma and hepatocellular carcinoma, both of which are highly vascularized, angiogenesis-dependent tumors.

Soft tissue sarcomas, including liposarcoma, similarly show frequent PDGFR pathway activation and tumor vascular dependence, providing a plausible mechanistic bridge. Dedifferentiated liposarcoma additionally shows PTEN down-regulation, which may interact with RAF/AKT signaling (PMID 23416162). This mechanistic overlap is reflected in the completed Phase 2 SWOG trial (S0505) that directly tested sorafenib in advanced soft tissue sarcoma populations including liposarcoma subtypes.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00217620	Phase 2	Completed	51	Sorafenib (BAY 43-9006) tested in advanced soft tissue sarcomas including liposarcoma subtypes; direct drug-disease evidence
NCT02048371	Phase 2	Completed	131	SARC024 blanket protocol on oral regorafenib (structurally related, not sorafenib) in selected sarcoma subtypes — indirect supportive precedent only

Literature Evidence

PMID	Year	Type	Journal	Key Findings
21751200	2012	Phase 2 trial (SWOG S0505)	Cancer	Sorafenib tested in advanced soft tissue sarcoma patients with limited therapeutic options; a multitargeted kinase inhibitor of RAF, VEGFR1-3, PDGFR-β, and c-kit
24554062	2014	Phase 1 trial	Annals of Surgical Oncology	Neoadjuvant sorafenib + conformal radiotherapy in extremity soft tissue sarcoma; synergy hypothesis with antiangiogenic therapy
22987955	2012	Review	Annals of Oncology	Histology-driven medical therapy in soft tissue sarcomas, including liposarcoma-specific agent activity
24712007	2014	Review	Magyar Onkologia	Histological subtype-based medical treatment approach for soft tissue sarcomas
36003796	2022	Review	Frontiers in Oncology	PDOX models identify effective combination therapies (CDK inhibitor palbociclib) for sarcoma
18413802	2008	Preclinical	Molecular Cancer Therapeutics	Sorafenib inhibits growth/MAPK signaling in malignant peripheral nerve sheath and dedifferentiated liposarcoma cell lines
23416162	2013	Preclinical (xenograft)	American Journal of Pathology	Dedifferentiated liposarcoma xenograft models reveal PTEN down-regulation as a malignant signature, relevant to PI3K/RAF pathway inhibition
25075796	2014	Case report	Anti-Cancer Drugs	Response to trabectedin (different drug) in advanced synovial sarcoma — indirect sarcoma-class precedent only

Norway Market Information

Sorafenib is currently not marketed in Norway — no active authorizations are on record in the regulatory database (0 licenses).

Cytotoxicity

Item	Content
Cytotoxicity Classification	Targeted therapy (multi-kinase inhibitor targeting RAF/VEGFR/PDGFR), not conventional cytotoxic chemotherapy
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. Note: TFDA/regulatory-agency-level warning and contraindication data for this drug is flagged as a blocking data gap (DG001) — this must be resolved before a formal S1 safety assessment can proceed.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: A completed Phase 2 trial (SWOG S0505) and multiple mechanistically consistent preclinical studies support biological plausibility of sorafenib in soft tissue sarcoma/liposarcoma, but no liposarcoma-subtype-specific confirmatory trial exists, and formal safety-label data is currently unavailable.

To proceed, the following is needed:

TFDA/Norway package insert warnings and contraindications (DG001, blocking — required before S1 safety evaluation)
Formal DrugBank-sourced mechanism of action documentation (DG002)
Liposarcoma-subtype-specific trial data or subgroup analysis from existing sarcoma trials
A defined safety monitoring plan given the drug's antiangiogenic/kinase-inhibitor toxicity profile
Disclaimer

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