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First-Generation Tyrosine Kinase Inhibitors: Clinical Results

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Renal Cell Carcinoma

Abstract

Interferon-α (IFN-α) and interleukin-2 (IL-2) used to be the standard treatment for metastatic renal cell carcinoma (RCC), even at the beginning of the twenty-first century. However in recent years, increased understanding of the importance of angiogenesis in RCC progression has led to the development of the tyrosine kinase inhibitors (TKIs). TKIs have good oral bioavailability and have manageable side effects. More importantly, they have significant antitumoral efficacy with resulting prolongation of patient survival when used in the first-line setting or after failure of cytokine therapy.

In the phase III TARGET trial, treatment with sorafenib has been found to confer a survival advantage against placebo in patients who had previous cytokines. However, recent data from the AXIS and TIVO-1 trials have shown better efficacy and tolerability with the third-generation TKIs compared to sorafenib. Since the publication of its phase III trial in 2007, which demonstrated the superiority of sunitinib over IFN-α in treatment-naïve metastatic RCC, sunitinib has become a standard first-line therapy worldwide. Its efficacy has been found to be similar to the second-generation TKI pazopanib in the recent COMPARZ trial. The significant impact that sorafenib and sunitinib had on patients with advanced RCC has set the standards against which new therapies are measured. This chapter aims to summarize the clinical results of these first-generation of TKIs published thus far.

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Authors and Affiliations

  1. Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Box 193, Hills Road, Cambridge, CB2 0QQ, UK

    Han Hsi Wong M.B.Ch.B., Ph.D., M.R.C.P.(U.K.) & Tim Eisen

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  1. Han Hsi Wong M.B.Ch.B., Ph.D., M.R.C.P.(U.K.)
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  2. Tim Eisen
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Correspondence to Han Hsi Wong M.B.Ch.B., Ph.D., M.R.C.P.(U.K.) .

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  1. Taussig Cancer Center, Cleveland Clinic, Pepper Pike, Ohio, USA

    Ronald M. Bukowski

  2. Division of Hematology Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA

    Robert A. Figlin

  3. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA

    Robert J. Motzer

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Wong, H.H., Eisen, T. (2015). First-Generation Tyrosine Kinase Inhibitors: Clinical Results. In: Bukowski, R., Figlin, R., Motzer, R. (eds) Renal Cell Carcinoma. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1622-1_8

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