臨床泌尿器科67巻1号

2013年01月発行

特集 分子標的薬時代開幕5年目を迎えた進行腎癌の治療戦略の現状と展望

効果，副作用，予後に関するバイオマーカー

著者： 湯浅健¹ 齋藤一隆² 藤井靖久¹²

所属機関： ¹公益財団法人がん研究会有明病院泌尿器科 ²東京医科歯科大学大学院腎泌尿器外科

ページ範囲：P.75 - P.81

文献概要

要旨　進行腎癌に対する分子標的治療は，癌化の原因となる“標的蛋白質”を阻害するのでなく，癌の増殖“シグナル”を抑える。標的となるシグナルは正常細胞にも必要なものであり，副作用も多く，完全寛解が少ないことにつながると考えられている。したがって，多くの症例の治療目標は副作用のマネージメントをし，QOLを保ちながら，生存期間を延長することと考えられる。本稿では，現時点で最もよく使用されているスニチニブを中心に，効果，副作用に関連するバイオマーカーについて，臨床因子，遺伝子因子，循環蛋白質や循環腫瘍細胞，そして，副作用などその他の要因に項目を分けて解説する。

参考文献

1）Motzer RJ, Murphy BA, Bacik J, et al：Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 20：289-296, 2001

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

3）Heng DY, Xie W, Regan MM, et al：Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents：results from a large, multicenter study. J Clin Oncol 27：5794-5799, 2009

4）Choueiri TK, Garcia JA, Elson P, et al：Clinical factors associated with outcome in patients with metastatic clear-cell renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy. Cancer 110：543-550, 2007

5）Patil S, Figlin RA, Hutson TE, et al：Prognostic factors for progression-free and overall survival with sunitinib targeted therapy and with cytokine as first-line therapy in patients with metastatic renal cell carcinoma. Ann Oncol 22：295-300, 2011

6）Bamias A, Karadimou A, Lampaki S, et al：Prognostic stratification of patients with advanced renal cell carcinoma treated with sunitinib：comparison with the Memorial Sloan-Kettering prognostic factors model. BMC Cancer 10：45, 2010

7）Yuasa T, Tsuchiya N, Horikawa Y, et al：Clinical efficacy and prognostic factors for overall survival in Japanese patients with metastatic renal cell cancer treated with sunitinib. BJU Int 109：1349-1354, 2012

8）Ramsey S, Lamb GW, Aitchison M, et al：Evaluation of an inflammation-based prognostic score in patients with metastatic renal cancer. Cancer 109：205-212, 2007

9）Saito K, Tatokoro M, Fujii Y, et al：Impact of C-reactive protein kinetics on survival of patients with metastatic renal cell carcinoma. Eur Urol 55：1145-1153, 2009

10）Yasuda Y, Saito K, Yuasa T, et al：Prognostic impact of pretreatment C-reactive protein for patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors. Int J Clin Oncol（in press）

11）van Erp NP, Eechoute K, van der Veldt AA, et al：Pharmacogenetic pathway analysis for determination of sunitinib-induced toxicity. J Clin Oncol 27：4406-4412, 2009

12）van der Veldt AA, Eechoute K, Gelderblom H, et al：Genetic polymorphisms associated with a prolonged progression-free survival in patients with metastatic renal cell cancer treated with sunitinib. Clin Cancer Res 17：620-629, 2011

13）Kawahara H, Noguchi K, Katayama K, et al：Pharmacological interaction with sunitinib is abolished by a germ-line mutation（1291T＞C）of BCRP/ABCG2 gene. Cancer Sci 101：1493-1500, 2010

14）Mizuno T, Terada T, Kamba T, et al：ABCG2 421C＞A polymorphism and high exposure of sunitinib in a patient with renal cell carcinoma. Ann Oncol 21：1382-1383, 2010

15）Van Erp NP, Mathijssen RHJ, Van der Veldt AA, et al：Myelosuppression by sunitinib is flt-3 genotype dependent. Br J Cancer 103：757-758, 2010

16）Xu CF, Bing NX, Ball HA, et al：Pazopanib efficacy in renal cell carcinoma：evidence for predictive genetic markers in angiogenesis-related and exposure-related genes. J Clin Oncol 29：2557-2564, 2011

17）Rini BI, Michaelson MD, Rosenberg JE, et al：Antitumor activity and biomarker analysis of sunitinib in patients with bevacizumab-refractory metastatic renal cell carcinoma. J Clin Oncol 26：3743-3748, 2008

18）Gruenwald V, Beutel G, Schuch-Jantsch S, et al：Circulating endothelial cells are an early predictor in renal cell carcinoma for tumor response to sunitinib. BMC Cancer 10：695, 2010

19）Porta C, Paglino C, De Amici M, et al：Predictive value of baseline serum vascular endothelial growth factor and neutrophil gelatinase-associated lipocalin in advanced kidney cancer patients receiving sunitinib. Kidney Int 77：809-815, 2010

20）Peña C, Lathia C, Shan M, et al：Biomarkers predicting outcome in patients with advanced renal cell carcinoma：results from sorafenib phase Ⅲ Treatment Approaches in Renal Cancer Global Evaluation Trial. Clin Cancer Res 16：4853-4863, 2010

21）Rixe O, Billemont B and Izzedine H：Hypertension as a predictive factor of Sunitinib activity. Ann Oncol 18：1117, 2007

22）Schmidinger M, Vogl UM, Bojic M, et al：Hypothyroidism in patients with renal cell carcinoma：blessing or curse? Cancer 117：534-544, 2011

23）Yuasa T, Urakami S, Yamamoto S, et al：Tumor size is a potential predictor of the response to tyrosine kinase inhibitors in renal cell cancer. Urology 77：831-815, 2011

24）Yuasa T, Takahashi S, Hatake K, et al：Biomarkers to predict response to sunitinib therapy and prognosis in metastatic renal cell cancer. Cancer Science 102：1949-1957, 2011