Drugs of interest to pathologists
Drugs related to surgical pathology
Sorafenib tosylate
Copyright: (c) 2002-2019, PathologyOutlines.com, Inc.
PubMed Search: Nexavar [title]
Drugs related to surgical pathology
Sorafenib tosylate
Author: Him G. Kwee, M.D.
Topic Completed: 1 December 2011
Minor changes: 22 August 2019
Copyright: (c) 2002-2019, PathologyOutlines.com, Inc.
PubMed Search: Nexavar [title]
Table of Contents
Definition / general | Trade name | Clinical information | Uses by pathologists | Side effectsCite this page: Kwee HG. Sorafenib tosylate. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/drugsnexavar.html. Accessed August 6th, 2020.
Definition / general
- Multitargeted kinase inhibitor
Trade name
- Nexavar®
Clinical information
Approved by US Food and Drug Administration for:
- Advanced or metastatic renal cell carcinoma (RCC)
- Unresectable hepatocellular carcinoma (HCC, PDR staff: Physician’s Desk Reference, 65th Edition, 2011)
- Used off label for GIST (gastrointestinal stromal tumor) that is resistant to imatinib and sunitinib and sometimes also resistant to nilotinib (Drugs 2015;75:1323)
- Cost: approximately $5,400 per month in 2008 (Medpage Today, July 23, 2008)
Uses by pathologists
- Inhibits intracellular kinases CRAF, BRAF, mutated BRAF and cell surface kinases KIT, FLT-3 (FMS-like tyrosine kinase receptor 3), RET (rearranged during transfection proto-oncogene), VEGFR 1,2 and 3 and PDGFR beta (platelet derived growth factor receptor beta); thus, inhibits tumor cell division and proliferation and also blocks tumor angiogenesis (PDR staff: Physician’s Desk Reference, 65th Edition, 2011)
- Hepatocellular carcinoma: effective because it inhibits hepatocyte growth factor (HGF) mediated epithelial mesenchymal transition (EMT), a key developmental program that is activated during cancer invasion and metastasis and mitogen activated protein kinase (MAPK) signaling, which also inhibits EMT in HCC cells (Mol Cancer Ther 2011;10:169); sunitinib is not effective for HCC
- Contraindicated in patients with squamous cell lung carcinoma treated with carboplatin and paclitaxel (PDR staff: Physician’s Desk Reference, 65th Edition, 2011)
- Renal cell carcinoma: clear cell RCC is currently the most amenable to targeted therapy that is available; sunitinib is more effective than sorafenib but there are other drugs such as bevacizumab, pazopanib, everolimus and temsirolimus that are also approved by the FDA for RCC (National Cancer Institute: Renal Cell Cancer Treatment (PDQ®) – Health Professional Version [Accessed 14 December 2018]); most clinical trials involve patients with clear cell RCC; little is known about the optimal treatment for non clear cell RCC
- Immunohistochemical stains for carbonic anhydrase IX, AMACR, CD 117, CK 7 and CD 10 are useful to classify RCC subtypes, which has potential therapeutic implications (Am J Surg Pathol 2011;35:949)
- Sunitinib, pazopanib and bevacizumab plus interferon alpha are all listed with a category 1 designation for clear cell RCC; temsirolimus is listed with a category 1 designation for both clear cell and non clear cell RCC (J Natl Compr Canc Netw 2011;9:S1)
- Sarcomatoid RCC does not respond well to targeted therapy unless the sarcomatoid elements arise from clear cell RCC and the sarcomatoid component is less than 20% of the tumor (J Clin Oncol 2009;27:235)
Side effects
- Reversible diffuse yellow discoloration of the skin without hyperbilirubinemia or discoloration of sclerae and mucous membranes; also occurs with sunitinib (South Med J 2007;100:328)
- Reversible posterior leukoencephalopathy (J Clin Oncol 2006;24:e48)
- Proteinuria (J Natl Compr Canc Netw 2011;9:S1)
- Reversible erythrocytosis (J Clin Oncol 2008;26:4047)
- Hypophophatemia (J Natl Compr Canc Netw 2011;9:S1)
- Increase in serum lipase and amylase with or without clinical acute pancreatitis (PDR staff: Physician’s Desk Reference, 65th Edition, 2011)
