Critical appraisal of sorafenib in the treatment of Chinese patients with renal cell carcinoma

OncoTargets and Therapy Dovepress open access to scientific and medical research Review Open Access Full Text Article OncoTargets and Therapy downloaded from https://www.dovepress.com/ by 51.68.7.205 on 12-Jul-2018 For personal use only. Critical appraisal of sorafenib in the treatment of Chinese patients with renal cell carcinoma This article was published in the following Dove Press journal: OncoTargets and Therapy 6 June 2014 Number of times this article has been viewed Ding-Wei Ye Hai-Liang Zhang Department of Urology, Fudan University Shanghai Cancer Center, 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China 1 Introduction Correspondence: Ding-Wei Ye Department of Urology, Fudan University, Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, People’s Republic of China Tel +86 6417 5590 1807 Fax +86 6443 8640 Email Renal cell carcinoma (RCC) is the third most common malignancy of the genitourinary system, accounting for about 3% of all adult malignancies and 2% of all cancer deaths.1 In the People’s Republic of China, the incidence of RCC has increased significantly in the past 10 years, and is currently estimated to be six per 100,000 people per year. Around 78,000 new cases occur each year, of which 19,500 (25%) are at a late stage and 20,000 deaths occur each year due to this cancer.2 In Shanghai, the incidence of RCC reached 14.2 per 100,000 people in 2009, and became the ninth most common malignancy in men.3 RCC is highly resistant to chemotherapy, and its response to cytokine therapy, including high-dose interleukin-2 and/or interferon-alpha, is less than 20%.4 Moreover, the toxicity of cytokine therapy, particularly interleukin-2, makes this treatment only appropriate for a small number of selected cases. For decades, the outcome for patients with metastatic disease was dismal, and the 5-year overall survival rate was less than 10%, despite systemic treatment.5 Recently, treatment strategies for metastatic RCC have changed dramatically due to the introduction of several new agents targeting tumor angiogenesis and intracellular pathways mediating growth and proliferation. Among these agents are tyrosine kinase inhibitors such as sorafenib, sunitinib, pazopanib, and axitinib; mammalian target of rapamycin (mTOR) inhibitors such as temsirolimus and everolimus; and the 925 submit your manuscript | www.dovepress.com OncoTargets and Therapy 2014:7 925–935 Dovepress © 2014 Ye and Zhang. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php http://dx.doi.org/10.2147/OTT.S41828 Powered by TCPDF (www.tcpdf.org) Abstract: Renal cell carcinoma (RCC) accounts for 3% of all malignancies, and is the most aggressive cancer of the genitourinary system. Metastatic RCC is naturally resistant to chemotherapy and radiotherapy, and immunotherapy is of little benefit. In recent years, the emergence of molecular-targeted therapies has largely changed the therapeutic approach to metastatic RCC. These novel multikinase inhibitors have now become first-choice therapy because of their activity in inhibiting both cell proliferation and tumor angiogenesis. Sorafenib is the first tyrosine kinase inhibitor found to be effective in treating patients with metastatic RCC. Due to its good efficacy and safety, this agent is recommended as both first-line and second-line therapy for metastatic RCC in the People’s Republic of China. Sorafenib seems to be more effective in patients of Chinese ethnicity than in western patients, and is well tolerated with a manageable toxicity profile, even at higher dosages and when used in combination with other anticancer agents. Novel biomarkers for predicting the efficacy of sorafenib have potential clinical value for guiding individualized targeted therapy. Keywords: kidney cancer, renal cell carcinoma, sorafenib, tyrosine kinase inhibitor OncoTargets and Therapy downloaded from https://www.dovepress.com/ by 51.68.7.205 on 12-Jul-2018 For personal use only. Ye and Zhang anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab, usually given in combination with interferon.6 Sorafenib (Nexavar®, Bayer Healthcare Pharmaceuticals, Wayne, NJ, USA, and Onyx Pharmaceuticals, South San Francisco, CA, USA) is a multi-targeting tyrosine kinase inhibitor against VEGF receptors, platelet-derived growth factor receptors, Fms-like tyrosine kinase 3, RET, and KIT, as well as the RAF serine/threonine kinases B-RAF and C-RAF.7 The efficacy of sorafenib in RCC has been confirmed in Phase II and Phase III trials, leading to its approval by the US Food and Drug Administration in December 2005 as the first targeted agent to show clinical activity in RCC.6,8–10 Ten months later, sorafenib was approved by the State Food and Drug Administration in the People’s Republic of China as first-line/second-line treatment for advanced RCC. This paper reviews the available data on the efficacy, safety, and clinical application status of sorafenib in Chinese patients with RCC. Efficacy of sorafenib as first/secondline treatment after cytokine therapy in advanced RCC Since December 2006, more than 4,000 Chinese patients with advanced RCC have received sorafenib. Because most patients in the People’s Republic of China cannot afford the cost of continued sorafenib treatment, in April 2007, the China Charity Federation accepted donations from Bayer Healthcare Products Co, Ltd and established the Nexavar (sorafenib) patient assistance program to enable more patients with advanced RCC to have access to sorafenib. As of May 2013, over 3,000 patients have been enrolled in this program. After 3 months of treatment, patients who fit this program are able to receive free sorafenib until progression of their disease. Most of the data on sorafenib in Chinese patients with RCC have been reported retrospectively in local medical journals, and only four studies have been published in non-Chinese language journals or as abstracts of papers p resented at American Society of Clinical Oncology meetings. In the first of these studies, Sun et al10 reported the results of an open-label, multicenter, noncontrolled, investigator-initiated trial in Chinese patients with advanced RCC. The clinical benefit rate (complete response + partial response + stable disease) was 84.2% in the 57 patients evaluated, and the objective response rate (complete response + partial response) was 21%. Median prog (...truncated)