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Sorafenib

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Small Molecules in Oncology

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 184))

Abstract

Sorafenib (BAY 43–9006, Nexavar®) is a novel oral kinase inhibitor that targets multiple tyrosine kinases in vivo and in vitro. Main targets are receptor tyrosine kinase pathways frequently deregulated in cancer such as the raf–ras pathway, vascular endothelial growth factor (VEGF) pathway, and FMS-like tyrosine kinase 3 (FLT3). Sorafenib was approved by the FDA in fast track for advanced renal cell cancer and hepatocellular cancer and shows good clinical activity in thyroid cancer. Multiple clinical trials are undertaken to further investigate the role of sorafenib alone or in combination for the treatment of various tumor entities.

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References

  • Abou-Alfa GK, Schwartz L, Ricci S, Amadori D, Santoro A, Figer A et al (2006) Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol 24:4293–4300

    Article  PubMed  CAS  Google Scholar 

  • Auclair D, Miller D, Yatsula V, Pickett W, Carter C, Chang Y et al (2007) Antitumor activity of sorafenib in FLT3-driven leukemic cells. Leukemia 21:439–445

    Article  PubMed  CAS  Google Scholar 

  • Awada A, Hendlisz A, Gil T, Bartholomeus S, Mano M, de Valeriola D et al (2005) Phase I safety and pharmacokinetics of BAY 43–9006 administered for 21 days on/7 days off in patients with advanced, refractory solid tumours. Br J Cancer 92:1855–1861

    Article  PubMed  CAS  Google Scholar 

  • Azad NS, Posadas EM, Kwitkowski VE, Steinberg SM, Jain L, Annunziata CM et al (2008) Combination targeted therapy with sorafenib and bevacizumab results in enhanced toxicity and antitumor activity. J Clin Oncol 26:3709–3714

    Article  PubMed  CAS  Google Scholar 

  • Carlomagno F, Anaganti S, Guida T, Salvatore G, Troncone G, Wilhelm SM et al (2006) BAY 43–9006 inhibition of oncogenic RET mutants. J Natl Cancer Inst 98:326–334

    Article  PubMed  CAS  Google Scholar 

  • Carter CA, Chen C, Brink C, Vincent P, Maxuitenko YY, Gilbert KS et al (2007) Sorafenib is efficacious and tolerated in combination with cytotoxic or cytostatic agents in preclinical models of human non-small cell lung carcinoma. Cancer Chemother Pharmacol 59:183–195

    Article  PubMed  CAS  Google Scholar 

  • Chang YS, Adnane J, Trail PA, Levy J, Henderson A, Xue D et al (2007) Sorafenib (BAY 43–9006) inhibits tumor growth and vascularization and induces tumor apoptosis and hypoxia in RCC xenograft models. Cancer Chemother Pharmacol 59:561–574

    Article  PubMed  CAS  Google Scholar 

  • Chi KN, Ellard SL, Hotte SJ, Czaykowski P, Moore M, Ruether JD et al (2008) A phase II study of sorafenib in patients with chemo-naive castration-resistant prostate cancer. Ann Oncol 19:746–751

    Article  PubMed  CAS  Google Scholar 

  • Clark JW, Eder JP, Ryan D, Lathia C, Lenz HJ (2005) Safety and pharmacokinetics of the dual action Raf kinase and vascular endothelial growth factor receptor inhibitor, BAY 43–9006, in patients with advanced, refractory solid tumors. Clin Cancer Res 11:5472–5480

    Article  PubMed  CAS  Google Scholar 

  • Dahut WL, Scripture C, Posadas E, Jain L, Gulley JL, Arlen PM et al (2008) A phase II clinical trial of sorafenib in androgen-independent prostate cancer. Clin Cancer Res 14:209–214

    Article  PubMed  CAS  Google Scholar 

  • Eisen T, Ahmad T, Flaherty KT, Gore M, Kaye S, Marais R et al (2006) Sorafenib in advanced melanoma: a Phase II randomised discontinuation trial analysis. Br J Cancer 95:581–586

    Article  PubMed  CAS  Google Scholar 

  • Elser C, Siu LL, Winquist E, Agulnik M, Pond GR, Chin SF et al (2007) Phase II trial of sorafenib in patients with recurrent or metastatic squamous cell carcinoma of the head and neck or nasopharyngeal carcinoma. J Clin Oncol 25:3766–3773

    Article  PubMed  CAS  Google Scholar 

  • Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M et al (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356:125–134

    Article  PubMed  CAS  Google Scholar 

  • Flaherty KT, Schiller J, Schuchter LM, Liu G, Tuveson DA, Redlinger M et al (2008) A phase I trial of the oral, multikinase inhibitor sorafenib in combination with carboplatin and paclitaxel. Clin Cancer Res 14:4836–4842

    Article  PubMed  CAS  Google Scholar 

  • Friday BB, Adjei AA (2008) Advances in targeting the Ras/Raf/MEK/Erk mitogen-activated protein kinase cascade with MEK inhibitors for cancer therapy. Clin Cancer Res 14:342–346

    Article  PubMed  CAS  Google Scholar 

  • Gatzemeier U, Blumenschein G, Fosella F, Simantov R, Elting J, Bigwood D et al (2006) Phase II trial of single-agent sorafenib in patients with advanced non-small cell lung carcinoma. J Clin Oncol (Meeting Abstracts) 24:7002

    Google Scholar 

  • Gupta-Abramson V, Troxel AB, Nellore A, Puttaswamy K, Redlinger M, Ransone K et al (2008) Phase II trial of sorafenib in advanced thyroid cancer. J Clin Oncol 26:4714–4719

    Article  PubMed  CAS  Google Scholar 

  • Gutierrez M, Giaccone G (2008) Antiangiogenic therapy in nonsmall cell lung cancer. Curr Opin Oncol 20:176–182

    Article  PubMed  CAS  Google Scholar 

  • Hicklin DJ, Ellis LM (2005) Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 23:1011–1027

    Article  PubMed  CAS  Google Scholar 

  • Hotte SJ, Hirte HW (2002) BAY 43–9006: early clinical data in patients with advanced solid malignancies. Curr Pharm Des 8:2249–2253

    Article  PubMed  CAS  Google Scholar 

  • Karasarides M, Chiloeches A, Hayward R, Niculescu-Duvaz D, Scanlon I, Friedlos F et al (2004) B-RAF is a therapeutic target in melanoma. Oncogene 23:6292–6298

    Article  PubMed  CAS  Google Scholar 

  • Kim S, Yazici YD, Calzada G, Wang ZY, Younes MN, Jasser SA et al (2007) Sorafenib inhibits the angiogenesis and growth of orthotopic anaplastic thyroid carcinoma xenografts in nude mice. Mol Cancer Ther 6:1785–1792

    Article  PubMed  CAS  Google Scholar 

  • Kupsch P, Henning BF, Passarge K, Richly H, Wiesemann K, Hilger RA et al (2005) Results of a phase I trial of sorafenib (BAY 43–9006) in combination with oxaliplatin in patients with refractory solid tumors, including colorectal cancer. Clin Colorectal Cancer 5:188–196

    Article  PubMed  Google Scholar 

  • Liu L, Cao Y, Chen C, Zhang X, McNabola A, Wilkie D et al (2006) Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res 66:11851–11858

    Article  PubMed  CAS  Google Scholar 

  • Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359: 378–390

    Article  PubMed  CAS  Google Scholar 

  • Lyons JF, Wilhelm S, Hibner B, Bollag G (2001) Discovery of a novel Raf kinase inhibitor. Endocr Relat Cancer 8:219–225

    Article  PubMed  CAS  Google Scholar 

  • McDermott DF, Sosman JA, Gonzalez R, Hodi FS, Linette GP, Richards J et al (2008) Double-blind randomized phase II study of the combination of sorafenib and dacarbazine in patients with advanced melanoma: a report from the 11715 Study Group. J Clin Oncol 26:2178–2185

    Article  PubMed  CAS  Google Scholar 

  • McInnes C, Sykes BD (1997) Growth factor receptors: structure, mechanism, and drug discovery. Biopolymers 43:339–366

    Article  PubMed  CAS  Google Scholar 

  • Moore M, Hirte HW, Siu L, Oza A, Hotte SJ, Petrenciuc O et al (2005) Phase I study to determine the safety and pharmacokinetics of the novel Raf kinase and VEGFR inhibitor BAY 43–9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors. Ann Oncol 16:1688–1694

    Article  PubMed  CAS  Google Scholar 

  • Oka H, Chatani Y, Hoshino R, Ogawa O, Kakehi Y, Terachi T et al (1995) Constitutive activation of mitogen-activated protein (MAP) kinases in human renal cell carcinoma. Cancer Res 55: 4182–4187

    PubMed  CAS  Google Scholar 

  • Ranze O, Hofmann E, Distelrath A, Hoeffkes HG (2007) Renal cell cancer presented with leptomeningeal carcinomatosis effectively treated with sorafenib. Onkologie 30:450–451

    Article  PubMed  Google Scholar 

  • Ratain MJ, Eisen T, Stadler WM, Flaherty KT, Kaye SB, Rosner GL et al (2006) Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 24:2505–2512

    Article  PubMed  CAS  Google Scholar 

  • Richly H, Kupsch P, Passage K, Grubert M, Hilger RA, Kredtke S et al (2003) A phase I clinical and pharmacokinetic study of the Raf kinase inhibitor (RKI) BAY 43–9006 administered in combination with doxorubicin in patients with solid tumors. Int J Clin Pharmacol Ther 41:620–621

    PubMed  CAS  Google Scholar 

  • Richly H, Kupsch P, Passage K, Grubert M, Hilger RA, Voigtmann R et al (2004) Results of a phase I trial of BAY 43–9006 in combination with doxorubicin in patients with primary hepatic cancer. Int J Clin Pharmacol Ther 42:650–651

    PubMed  CAS  Google Scholar 

  • Safarinejad MR (2008) Safety and efficacy of sorafenib in patients with castrate resistant prostate cancer: a Phase II study. Urol Oncol Article in Press

    Google Scholar 

  • Salvatore G, De Falco V, Salerno P, Nappi TC, Pepe S, Troncone G et al (2006) BRAF is a therapeutic target in aggressive thyroid carcinoma. Clin Cancer Res 12:1623–1629

    Article  PubMed  CAS  Google Scholar 

  • Savage DG, Antman KH (2002) Imatinib mesylate–a new oral targeted therapy. N Engl J Med 346:683–693

    Article  PubMed  CAS  Google Scholar 

  • Scagliotti GV, von Pawel J, Reck M, Cupit L, Cihon F, DiMatteo S et al (2008) Sorafenib plus ­carboplatin/paclitaxel in chemonaive patients with stage IIIb-IV non–small cell lung cancer (NSCLC): interim analysis (IA) results from the phase III, randomized, double-blind, placebo-controlled, escape (evaluation of sorafenib, carboplatin, and paclitaxel efficacy in NSCLC) trial. J Thorac Oncol 3:1–106

    Article  Google Scholar 

  • Sebolt-Leopold JS, Herrera R (2004) Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat Rev Cancer 4:937–947

    Article  PubMed  CAS  Google Scholar 

  • Sharma A, Trivedi NR, Zimmerman MA, Tuveson DA, Smith CD, Robertson GP (2005) Mutant V599EB-Raf regulates growth and vascular development of malignant melanoma tumors. Cancer Res 65:2412–2421

    Article  PubMed  CAS  Google Scholar 

  • Smalley KS, Xiao M, Villanueva J, Nguyen TK, Flaherty KT, Letrero R et al (2009) CRAF inhibition induces apoptosis in melanoma cells with non-V600E BRAF mutations. Oncogene 28:85–94

    Article  PubMed  CAS  Google Scholar 

  • Steinbild S, Mross K, Frost A, Morant R, Gillessen S, Dittrich C et al (2007) A clinical phase II study with sorafenib in patients with progressive hormone-refractory prostate cancer: a study of the CESAR Central European Society for Anticancer Drug Research-EWIV. Br J Cancer 97:1480–1485

    Article  PubMed  CAS  Google Scholar 

  • Stirewalt DL, Radich JP (2003) The role of FLT3 in haematopoietic malignancies. Nat Rev Cancer 3:650–665

    Article  PubMed  CAS  Google Scholar 

  • Strumberg D, Richly H, Hilger RA, Schleucher N, Korfee S, Tewes M et al (2005) Phase I clinical and pharmacokinetic study of the Novel Raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43–9006 in patients with advanced refractory solid tumors. J Clin Oncol 23:965–972

    Article  PubMed  CAS  Google Scholar 

  • Strumberg D, Voliotis D, Moeller JG, Hilger RA, Richly H, Kredtke S et al (2002) Results of phase I pharmacokinetic and pharmacodynamic studies of the Raf kinase inhibitor BAY 43–9006 in patients with solid tumors. Int J Clin Pharmacol Ther 40:580–581

    PubMed  CAS  Google Scholar 

  • Valcamonico F, Ferrari V, Amoroso V, Rangoni G, Simoncini E, Marpicati P et al (2009) Long-lasting successful cerebral response with sorafenib in advanced renal cell carcinoma. J Neurooncol 91:47–50

    Article  PubMed  Google Scholar 

  • Wang Z, Zhou J, Fan J, Qiu SJ, Yu Y, Huang XW et al (2008) Effect of rapamycin alone and in combination with sorafenib in an orthotopic model of human hepatocellular carcinoma. Clin Cancer Res 14:5124–5130

    Article  PubMed  CAS  Google Scholar 

  • Wilhelm S, Carter C, Lynch M, Lowinger T, Dumas J, Smith RA et al (2006) Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov 5:835–844

    Article  PubMed  CAS  Google Scholar 

  • Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H et al (2004) BAY 43–9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 64:7099–7109

    Article  PubMed  CAS  Google Scholar 

  • Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D et al (2008) DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res 36:D901–D906

    Article  CAS  Google Scholar 

  • Zhang W, Konopleva M, Shi YX, McQueen T, Harris D, Ling X et al (2008) Mutant FLT3: a direct target of sorafenib in acute myelogenous leukemia. J Natl Cancer Inst 100:184–198

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology and Oncology, Freiburg University Medical Center, Hugstetterstraße 55, 79102, Freiburg, Germany

    Jens Hasskarl

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  1. Jens Hasskarl
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Correspondence to Jens Hasskarl .

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  1. Medizinische Klinik III, SLK-Kliniken Heilbronn GmbH, Am Gesundbrunen 20-26, Heilbronn, 74078, Germany

    Uwe M. Martens

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Hasskarl, J. (2010). Sorafenib. In: Martens, U. (eds) Small Molecules in Oncology. Recent Results in Cancer Research, vol 184. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-01222-8_5

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  • DOI: https://doi.org/10.1007/978-3-642-01222-8_5

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  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-01221-1

  • Online ISBN: 978-3-642-01222-8

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