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Renal Cell Carcinoma pp 151–165Cite as

Sunitinib and Axitinib in Renal Cell Carcinoma

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Abstract

Sunitinib and axitinib are two oral, small-molecule agents that emerged from the same drug discovery program. They were rationally designed for selective inhibition of receptor tyrosine kinases (RTK), critically involved in human tumor malignancies. Sunitinib, the more extensively studied of the two, has demonstrated unprecedented antitumor activity in two phase II studies of cytokine-refractory metastatic renal cell carcinoma (mRCC) and statistically significant superiority over interferon-alfa as first-line therapy in patients with mRCC. These data have established sunitinib as a new reference standard of care in the first-line mRCC setting. Axitinib has also demonstrated significant antitumor activity in the cytokine-refractory mRCC setting, as well as shown encouraging results as second-line therapy in mRCC patients, refractory to prior RTK inhibition. In this chapter, we will discuss each compound in turn, briefly reviewing the preclinical and phase I development of each, before summarizing the clinical data available to date for the use of each in mRCC, including biomarker data for both drugs and discussion of data for sunitinib in different patient populations, in combination with other targeted agents, and at different dosing schedules.

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References

  1. Abrams TJ, Lee LB, Murray LJ, Pryer NK, Cherrington JM. SU11248 inhibits KIT and platelet-derived growth factor receptor beta in preclinical models of human small cell lung cancer. Mol Cancer Ther 2003;2:471–478.

    PubMed  CAS  Google Scholar 

  2. Mendel DB, Laird AD, Xin X, et al. In vivo antitumor activity of SU11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/pharmacodynamic relationship. Clin Cancer Res 2003;9:327–337.

    PubMed  CAS  Google Scholar 

  3. Murray LJ, Abrams TJ, Long KR, et al. SU11248 inhibits tumor growth and CSF-1R-dependent osteolysis in an experimental breast cancer bone metastasis model. Clin Exp Metastasis 2003;20:757–766.

    Article  PubMed  CAS  Google Scholar 

  4. O'Farrell AM, Abrams TJ, Yuen HA, et al. SU11248 is a novel FLT3 tyrosine kinase inhibitor with potent activity in vitro and in vivo. Blood 2003;101:3597–3605.

    Article  PubMed  Google Scholar 

  5. SUTENT (sunitinib malate) prescribing information. New York, NY: Pfizer Inc., February 2007. Accessed June 2007 at http://www.SUTENT.com

  6. Sakamoto JM. SU-11248 SUGEN. Curr Opin Investig Drugs 2004;5:1329–1339.

    PubMed  CAS  Google Scholar 

  7. Marzola P, Degrassi A, Calderan L, et al. Early antiangiogenic activity of SU11248 evaluated in vivo by dynamic contrast-enhanced magnetic resonance imaging in an experimental model of colon carcinoma. Clin Cancer Res 2005;11:5827–5832.

    Article  PubMed  CAS  Google Scholar 

  8. Demetri DG, George S, Heinrich MC, et al. Clinical activity and tolerability of the multi-targeted tyrosine kinase inhibitor SU11248 in patients with metastatic gastrointestinal stromal tumor refractory to imatinib mesylate. Proc Am Soc Clin Oncol 2003;22:814 (abstract 3,273).

    Google Scholar 

  9. Rosen L, Mulay M, Long J, et al. Phase I trial of SU11248, a novel tyrosine kinase inhibitor in advanced solid tumors. Proc Am Soc Clin Oncol 2003;22:191 (abstract 765).

    Google Scholar 

  10. Faivre S, Delbaldo C, Vera K, et al. Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J Clin Oncol 2006;24:25–35.

    Article  PubMed  CAS  Google Scholar 

  11. Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000;92:205–216.

    Article  PubMed  CAS  Google Scholar 

  12. Motzer RJ, Michaelson MD, Redman BG, et al. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J Clin Oncol 2006;24:16–24.

    Article  PubMed  CAS  Google Scholar 

  13. Motzer RJ, Rini BI, Bukowski RM, et al. Sunitinib in patients with metastatic renal cell carcinoma. JAMA 2006;295:2516–2524.

    Article  PubMed  CAS  Google Scholar 

  14. Motzer RJ, Bacik J, Schwartz LH, et al. Prognostic factors for survival in previously treated patients with metastatic renal cell carcinoma. J Clin Oncol 2004;22:454–463.

    Article  PubMed  Google Scholar 

  15. Deprimo SE, Bello CL, Smeraglia J, et al. Soluble protein biomarkers of pharmacodynamic activity of the multitargeted tyrosine kinase inhibitor SU11248 in patients with metastatic renal cell carcinoma. 96th Annual Meeting of the American Association for Cancer Research, 16–20 April 2005, Anaheim, California (abstract 464).

    Google Scholar 

  16. Cella D, Lai JS, Chang CH, Peterman A, Slavin M. Fatigue in cancer patients compared with fatigue in the general United States population. Cancer 2002;94:528–538.

    Article  PubMed  Google Scholar 

  17. Beaumont JL, Cella D, Li JZ, et al. Sunitinib Malate (SU11248): efficacy and tolerability in solid tumors. Presented at the Cancer and Kinases Meeting, Santa Fe, New Mexico, USA, February 14–19, 2006.

    Google Scholar 

  18. Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007;356:115–124.

    Article  PubMed  CAS  Google Scholar 

  19. Figlin RA, Hutson TE, Tomczak P, et al. Overall survival with sunitinib versus interferon (IFN)-alfa as first-line treatment of metastatic renal cell carcinoma (mRCC). Presented at the 44th Annual Meeting of the American Society of Clinical Oncology, Chicago, Illinois, USA, May 30–June 3, 2008 (abstract 5024). Accessed November 2008 at http://www.ASCO.org

  20. Srinivas S, Roigas J, Gillessen S, et al. Continuous daily administration of sunitinib in patients with cytokine-refractory metastatic renal cell carcinoma: updated results. Presented at the 43rd Annual Meeting of the American Society of Clinical Oncology, Chicago, Illinois, USA, June 1–5, 2007 (abstract 5,040). Accessed June 2007 at http://www.ASCO.org

  21. George DJ, Michaelson MD, Rosenberg JE, et al. Phase 2 trial of sunitinib in bevacizumab-refractory metastatic renal cell carcinoma (mRCC): updated results and analysis of circulating biomarkers. Presented at the 43rd Annual Meeting of the American Society of Clinical Oncology, Chicago, Illinois, USA, June 1–5, 2007 (abstract 5,035). Accessed June 2007 at http://www.ASCO.org

  22. Patel PH, Kondagunta G V, Redman BG, et al. Phase I/II study of sunitinib malate in combination with Gefitinib in patients with metastatic renal cell carcinoma (mRCC). Presented at the 43rd Annual Meeting of the American Society of Clinical Oncology, Chicago, Illinois, USA, June 1–5, 2007 (abstract 5,097). Accessed June 2007 at http://www.ASCO.org

  23. Gore ME, Porta C, Oudard S, et al. Sunitinib in metastatic renal cell carcinoma (mRCC): preliminary assessment in an expanded access trial with subpopulation analysis. Presented at the 43rd Annual Meeting of the American Society of Clinical Oncology, Chicago, Illinois, USA, June 1–5, 2007 (abstract 5,010). Accessed June 2007 at http://www.ASCO.org

  24. United States Pharmacopeia (USP). Dictionary of United States Adopted Names (USAN) and International Drug Names (2005–2006 published names). Accessed July 2007 at http://www.ama-assn.org

  25. Hu-Lowe D, Hallin M, Feeley R, et al. Characterization of potency and activity of the VEGF/ PDGF receptor tyrosine kinase inhibitor AG013736. Proc Am Assoc Cancer Res 2002;43 (abstract A5356).

    Google Scholar 

  26. Hu-Lowe D, Heller D, Brekken J, et al. Pharmacological activities of AG013736, a small molecule inhibitor of VEGF/PDGR receptor tyrosine kinases. Proc Am Assoc Cancer Res 2002;43 (abstract A5357).

    Google Scholar 

  27. Wickman G, Hallin M, Dillon R, et al. Further characterization of the potent VEGF/PDGF receptor tyrosine kinase inhibitor, AG013736, in preclinical tumor models for its antiangiogen-esis and antitumor activity. Proc Am Assoc Cancer Res 2003;44 (abstract A3780).

    Google Scholar 

  28. Hu-Lowe D, Grazzini M. Significant enhancement of anti-tumor efficacy of VEGF/PDGF receptor tyrosine kinase inhibitor AG-013736 in combination with docetaxel in chemo-refrac-tory and/or orthotopic xenograft tumor models in mice. Proc Am Assoc Cancer Res 2005;46 (abstract 2032).

    Google Scholar 

  29. Inai T, Mancuso M, Hashizume H, et al. Inhibition of vascular endothelial growth factor (VEGF) signaling in cancer causes loss of endothelial fenestrations, regression of tumor vessels, and appearance of basement membrane ghosts. Am J Pathol 2004;165:35–52.

    Article  PubMed  CAS  Google Scholar 

  30. Rugo HS, Herbst RS, Liu G, et al. Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: pharmacokinetic and clinical results. J Clin Oncol 2005;23:5474–5483.

    Article  PubMed  CAS  Google Scholar 

  31. Rini B, Rixe O, Bukowski R, et al. AG-013736, a VEGFR/PDGFR inhibitor, demonstrates anti-tumor activity in cytokine-refractory, metastatic renal cell carcinoma (RCC). Presented at the 41st Annual Meeting of the American Society of Clinical Oncology, Orlando, Florida, USA, May 13–17, 2005 (abstract 4509). Accessed June 2007 at http://www.ASCO.org

  32. Rixe O, Meric J, Bloch J, et al. Surrogate markers of activity of AG-013736, a multi-target tyrosine kinase receptor inhibitor, in metastatic renal cell cancer (RCC). Presented at the 41st Annual Meeting of the American Society of Clinical Oncology, Orlando, Florida, USA, May 13–17, 2005 (abstract 3003). Accessed June 2007 at http://www.ASCO.org

  33. Rini BI, Wilding GT, Hudes G, et al. Axitinib (AG-013736; AG) in patients (pts) with metastatic renal cell cancer (RCC) refractory to sorafenib. Presented at the 43rd Annual Meeting of the American Society of Clinical Oncology, Chicago, Illinois, USA, June 1–5, 2007 (abstract 5032). Accessed July 2007 at http://www.ASCO.org

  34. Demetri DG, van Oosterom AT, Garrett CR, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomized controlled trial. Lancet 2006;368:1329–1338.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY, 10021

    Robert J. Motzer

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  1. Robert J. Motzer
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Correspondence to Robert J. Motzer .

Editor information

Editors and Affiliations

  1. Cleveland Clinic Foundation, Cleveland Clinic Taussig Cancer Center and CCF Lerner College of Medicine of CWRU, Cleveland, OH

    Ronald M. Bukowski

  2. Division of Medical Oncology & Experimental Therapeutics, City of Hope National Medical, Center/Beckman Research Institute, Duarte, CA

    Robert A. Figlin

  3. Memorial-Sloan Kettering Cancer Center, New York, NY

    Robert J. Motzer

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© 2009 Humana Press, a part of Springer Science+Business Media, LLC

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Motzer, R.J. (2009). Sunitinib and Axitinib in Renal Cell Carcinoma. In: Bukowski, R.M., Figlin, R.A., Motzer, R.J. (eds) Renal Cell Carcinoma. Humana Press. https://doi.org/10.1007/978-1-59745-332-5_8

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  • DOI: https://doi.org/10.1007/978-1-59745-332-5_8

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-737-2

  • Online ISBN: 978-1-59745-332-5

  • eBook Packages: MedicineMedicine (R0)

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