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Drugs of interest to pathologists

Drugs related to surgical pathology and clinical pathology

Sorafenib tosylate


Author: Him G. Kwee, M.D. (see Reviewers/Authors page)
Revised: 10 December 2011, last major update November 2011
Copyright: (c) 2011, PathologyOutlines.com, Inc.

General
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● A multitargeted kinase inhibitor

Trade name
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● Nexavar

Clinical information
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Approved by US Food and Drug Administration for:
● Advanced or metastatic renal cell carcinoma (RCC)
● Unresectable hepatocellular carcinoma (HCC, Physician’s Desk Reference 2011)

● Used off-label for GIST (gastrointestinal stromal tumor) that is resistant to imatinib and sunitinib and sometimes also resistant to nilotinib (University of Chicago; Gastrointestinal Cancers Symposium, San Francisco, CA, abstract 2, January 20, 2011)
● Cost: approximately $5400 per month in 2008 (Medpage Today, July 23, 2008)

Use for pathologists
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● 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 (Physician’s Desk Reference 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 (Physician’s Desk Reference 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); 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 Suppl 1: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
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● 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 Suppl 1:S1)
● Reversible erythrocytosis (J Clin Oncol 2008;26:4047)
● Hypophophatemia (J Natl Compr Canc Netw 2011;9 Suppl 1:S1)
● Increase in serum lipase and amylase with or without clinical acute pancreatitis (Physician’s Desk Reference 2011)

End of Drugs > Drugs related to surgical pathology and clinical pathology > Sorafenib tosylate


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