Drugs of interest to pathologists
Drugs related to surgical pathology
Sorafenib tosylate

Author: Him G. Kwee, M.D. (see Authors page)

Revised: 5 December 2017, last major update November 2011

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Nexavar [title]

Cite this page: Kwee, H.G. Sorafenib tosylate. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/drugsnexavar.html. Accessed September 25th, 2018.
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 4 December 2017]); 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