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Sorafenib

In Advanced Renal Cancer

  • Adis Drug Evaluation
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Abstract

  • ▴ Sorafenib is an oral multikinase inhibitor that targets the mitogen-activated protein kinase signalling pathway and receptor tyrosine kinases involved in tumour proliferation and angiogenesis.

  • ▴ In the large, phase III, randomised, double-blind, multicentre Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) of patients with advanced clear-cell renal cell cancer in whom previous systemic therapy had failed, median progression-free survival was doubled in patients receiving sorafenib compared with those receiving placebo (5.9 vs 2.8mo).

  • ▴ Significantly more patients receiving sorafenib than those receiving placebo in the phase III trial experienced complete or partial responses or stable disease.

  • ▴ Age, risk-assessment score, prior treatment, metastasis in lung or liver, or time from diagnosis did not affect the improved progression-free survival in sorafenib recipients.

  • ▴ In a randomised, phase II discontinuation trial of patients with advanced renal cancer, in which only those showing stable disease with sorafenib were randomised to further sorafenib or placebo, more patients receiving sorafenib were free of progressive disease 12 weeks after randomisation than were those receiving placebo, and median progression-free survival was longer in sorafenib recipients.

  • ▴ In clinical trials, most drug-related adverse events were mild to moderate in severity. Grade 3/4 handfoot skin reaction and hypertension occurred more often with sorafenib than with placebo.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. van Spronsen DJ, de Weijer KJM, Mulders PFA, et al. Novel treatment strategies in clear-cell metastatic renal cell carcinoma. Anticancer Drugs 2005 Aug; 16 (7): 709–17

    Article  PubMed  Google Scholar 

  2. Eisen T. Renewed hope for patients with advanced renal cell cancer: Cinderella comes of age. Eur J Cancer 2005; 41 (8): 1106–8

    Article  PubMed  Google Scholar 

  3. Staehler M, Rohrmann K, Bachmann A, et al. Therapeutic approaches in metastatic renal cell carcinoma. BJU Int 2005; 95 (8): 1153–61

    Article  PubMed  Google Scholar 

  4. Favaro JP, George DJ. Targeted therapy in renal cell carcinoma. Expert Opin Investig Drugs 2005 Oct; 14 (10): 1251–8

    Article  PubMed  CAS  Google Scholar 

  5. Sridhar SS, Hedley D, Siu LL. Raf kinase as a target for anticancer therapeutics. Mol Cancer Ther 2005 Apr; 4 (4): 677–85

    Article  PubMed  CAS  Google Scholar 

  6. Wilhelm S, Carter C, Lynch M, et al. Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov 2006 Oct; 5 (10): 835–44

    Article  PubMed  CAS  Google Scholar 

  7. Wilhelm SM, Carter C, Tang LY, et al. 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 2004 Oct 1; 64 (19): 7099–109

    Article  PubMed  CAS  Google Scholar 

  8. Yu C, Bruzek LM, Meng XW, et al. The role of Mcl-1 downregulation in the proapoptotic activity of the multikinase inhibitor BAY 43-9006. Oncogene 2005 Jun 27; 24: 6861–9

    Article  PubMed  CAS  Google Scholar 

  9. Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007; 356 (2): 125–34

    Article  PubMed  CAS  Google Scholar 

  10. Elting J, Bigwood D, Brown-Shimer S, et al. Biomarkers associated with clinical outcomes in TARGETS, a phase III singleagent, placebo-controlled study of sorafenib in advanced renal cell carcinoma [abstract no. 2909]. 97th Proc Annu Meet Am Assoc Cancer Res 2006; 47: 683–4. Plus poster presented at the 97 th Annual Meeting of the American Association for Cancer Research; 2006 Apr 1–5; Washington DC

    Google Scholar 

  11. O’Dwyer PJ, Rosen M, Gallagher M, et al. Pharmacodynamic study of BAY 43-9006 in patients with metastatic renal cell carcinoma [abstract no. 3005]. J Clin Oncol 2005 Jun 1; 23 Suppl. (16 Pt I): 193s

    Google Scholar 

  12. Hilger RA, Kredtke S, Scheulen ME, et al. Correlation of ERK-phosphorylation and toxicities in patients treated with the Raf kinase inhibitor BAY 43-9006. Int J Clin Pharmacol Ther 2004 Nov; 42 (11): 648–9

    PubMed  CAS  Google Scholar 

  13. Veronese ML, Mosenkis A, Flaherty KT, et al. Mechanisms of hypertension associated with BAY 43-9006. J Clin Oncol 2006 Jan 30; 24 (9): 1329–31

    Article  Google Scholar 

  14. Strumberg D, Voliotis D, Moeller JG, et al. 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 2002 Dec; 40 (12): 580–1

    PubMed  CAS  Google Scholar 

  15. Awada A, Hendlisz A, Gil T, et al. 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 2005 May 23; 92 (10): 1855–61

    Article  PubMed  CAS  Google Scholar 

  16. Bayer HealthCare AG. Nexavar® (sorafenib) tablets 200 mg: prescribing information [online]. Available from URL: www.univgraph.com/bayer/inserts/nexavar.pdf [Accessed 2006 Feb 23]

  17. Lathia C, Lettieri J, Cihon F, et al. Lack of effect of ketoconazole-mediated CYP3A inhibition on sorafenib clinical pharmacokinetics. Cancer Chemother Pharmacol 2006 May 1; 57 (5): 685–92

    Article  PubMed  CAS  Google Scholar 

  18. Richly H, Kupsch P, Passage K, et al. 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 2003 Dec; 41 (12): 620–1

    PubMed  CAS  Google Scholar 

  19. Steinbild S, Baas F, Gmehling D, et al. Phase I study of BAY 43-9006 (sorafenib), a Raf kinase and VEGFR inhibitor, combined with irinotecan (CPT-11) in advanced solid tumors [abstract no. 3115]. J Clin Oncol 2005 Jun 1; 23 Suppl. (16 Pt I): 220s

    Google Scholar 

  20. Siu L, Awada A, Takimoto CH, et al. Phase I study of oral Raf-1 kinase inhibitor BAY 43-9006 with gemcitabine in patients with advanced solid tumors [abstract no. 828]. Proc Am Soc Clin Oncol 2003; 22: 207. Plus poster presented at the 39th Annual Meeting of the American Society of Clinical Oncology; 2003 May 31–Jun 3; Chicago (IL)

    Google Scholar 

  21. Awada A, Hendlisz A, Gil T, et al. A phase I study of BAY 43-9006, a novel Raf kinase and VEGFR inhibitor, in combination with [capecitabine] in patients with advanced solid tumors [abstract no. 381]. EJC Supplements 2004 Sep; 2 (8): 114

    Google Scholar 

  22. Flaherty KT, Lee RJ, Humphries R, et al. Phase I trial of BAY 43-9006 in combination with carboplatin (C) and paclitaxel (P) [abstract no. 2854]. Proc Am Soc Clin Oncol 2003; 22: 710. Plus poster presented at the 39th Annual Meeting of the American Society of Clinical Oncology; 2003 May 31–Jun 3; Chicago (IL)

    Google Scholar 

  23. Figer A, Moscovic M, Bulocinic S, et al. Phase I trial of BAY 43-9006 in combination with 5-fluorouracil (5-FU) and leucovorin (LCV) in patients with advanced refractory solid tumors [abstract no. 327P]. Ann Oncol 2004; 15 Suppl. 3: iii87–8. Plus poster presented at 29th Congress of the European Society of Medical Oncology; 2004 Oct 29–Nov 2; Vienna

    Google Scholar 

  24. Ratain MJ, Eisen T, Stadler WM, et al. Phase II placebocontrolled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 2006 Junl; 24 (16): 2505–12

    Article  PubMed  CAS  Google Scholar 

  25. Escudier B, Szczylik C, Eisen T, et al. Randomized phase III trial of the Raf kinase and VEGFR inhibitor sorafenib (BAY 43-9006) in patients with advanced renal cell carcinoma (RCC). J Clin Oncol 2005; 23 Suppl. (16 Pt 1): 1093. Plus oral presentation at the 41st Annual Meeting of the American Society of Clinical Oncology; 2005 May 13–17; Orlando (FL)

    Google Scholar 

  26. Maroto P, Villavicencio H, Pinol C, et al. Cost-effectiveness of sorafenib versus best supportive care in advanced renal cell carcinoma in Spain [abstract no. PCN16]. Value Health 2006; 9(6): A280

    Article  Google Scholar 

  27. Gao X, Reddy P, Dhanda R, et al. Cost-effectiveness of sorafenib versus best supportive care in advanced renal cell carcinoma [abstract no. 4604]. J Clin Oncol 2006 Jun 1; 24 (18 Pt 1 Suppl.): 242s

    Google Scholar 

  28. Dhanda R, Gondek K, Song J, et al. A quality of life, symptoms and survival comparison in kidney cancer patients receiving sorafenib versus placebo [abstract no. 447PD]. Ann Oncol 2006 Sep; 17 Suppl. 9: 147

    Google Scholar 

  29. Escudier B, Szczylik C, Demkow T, et al. Randomized phase II trial of the multi-kinase inhibitor sorafenib versus interferon (IFN) in treatment-naive patients with metastatic renal cell carcinoma (mRCC) [abstract no. 4501]. J Clin Oncol 2006; 24 Suppl. (18 Pt 1): 217s

    Google Scholar 

  30. Strumberg D, Awada A, Hirte H, et al. Pooled safety analysis of BAY 43-9006 (sorafenib) monotherapy in patients with advanced solid tumours: is rash associated with treatment outcome? Eur J Cancer 2006 Jan 17; 42: 548–56

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Antona J. Wagstaff.

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McKeage, K., Wagstaff, A.J. Sorafenib. Drugs 67, 475–483 (2007). https://doi.org/10.2165/00003495-200767030-00009

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  • DOI: https://doi.org/10.2165/00003495-200767030-00009

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