Efficacy and Safety of Sunitinib in Japanese Patients with Metastatic Renal Cell Carcinoma

Takahito Suyama, Takeshi Ueda, Satoshi Fukasawa, Atsushi Komaru, Masayuki Kobayashi, Yukio Naya, Naoki Nihei, Tomohiko Ichikawa

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DOI: 10.4236/jct.2011.23046                

Abstract

Objective: This study aim to assess the efficacy and safety of sunitinib in Japanese patients with metastatic renal cell carcinoma (mRCC) in general clinical practice. Patients and Methods: Non-selected fifty eight Japanese patients with mRCC were treated with sunitinib. Overall survival (OS) and time to treatment failure (TTF) were estimated. Response rate and safety profiles were also assessed. Results: Partial response, stable disease, and progressive disease were observed in 13 (22.4%), 26 (44.8%), and 19 (32.8%) patients, respectively. The median TTF was 5.4 months, and the median OS was 11.2 months. In the prior nephrectomy group, the median TTF was 9.0 months, and the median OS was 16.4 months. In the non-nephrectomy group, the median TTF was 1.1 months, and the median OS was 2.8 months. The most frequently occurring Grade 3/4 adverse events (AEs) were anorexia (17.2%), fatigue (12.1%), thrombocytopenia (13.8%), and anemia (12.1%). Conclusions: Sunitinib has a favorable risk/benefit profile in Japanese mRCC patients with a history of nephrectomy.

Keywords

Renal Cell Carcinoma, Metastasis, Sunitinib, Adverse Event

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	D. M. Parkin, F. Bray, J. Ferlay and P. Pisani, “Global Cancer Statistics, 2002,” A Cancer Journal for Clinicians, Vol. 55, No 2, 2005, pp. 74-108. doi:10.3322/canjclin.55.2.74
[2]	R. J. Motzer, N. H. Bander and D. M. Nanus, “Renal-Cell Carcinoma,” The New England Journal of Medicine, Vol. 335, No. 12, 1996, pp. 865-875. doi:10.1056/NEJM199609193351207
[3]	C. Coppin, F. Porzsolt, A. Awa, J. Kumpf, A. Coldman and T. Wilt, “Immunotherapy for Advanced Renal Cell Cancer,” Cochrane Database of Systematic Reviews, 2005, Vol. 1, p. 1425.
[4]	X. I. Na, G. Wu, C. K. Ryan, S. R. Schoen, P. A. di’Santagnese and E. M. Messing, “Overproduction of Vascular Endothelial Growth Factor Related to von Hippel-Lindau Tumor Suppressor Gene Mutations and Hypoxia-Inducible Factor-1alpha Expression in Renal Cell Carcinoma,” Journal of Urology, Vol. 170, No. 2 Part 1, 2003, pp. 588-592.
[5]	B. I. Rini and E. J. Small, “Biology and Clinical Development of Vascular Endothelial Growth Factor-Targeted Therapy in Renal Cell Carcinoma,” Journal of Clinical Oncology, Vol. 23, No. 5, 2005, pp. 1028-1043. doi:10.1200/JCO.2005.01.186
[6]	B. Escudier, A. Pluzanska, P. Koralewski, A. Ravaud, S. Bracarda, C. Szczylik, C. Chevreau, M. Filipek, B. Melichar, E. Bajetta, V. Gorbunova, J. O. Bay, I. Bodrogi, A. Jagiello-Gruszfeld, N. Moore and AVOREN Trial Investigators, “Bevacizumab Plus Interferon Alfa-2a for Treatment of Metastatic Renal Cell Carcinoma; a Randomized, Double-Blind Phase III Trial,” Lancet, Vol. 370, No. 9605, 2007, pp. 2103-2111. doi:10.1016/S0140-6736(07)61904-7
[7]	B. Escudier, T. Eisen, W. M. Stadler, C. Szczylik, S. Oudard, M. Siebels, S. Negrier, C. Chevreau, E. Solska, A. A. Desai, F. Rolland, T. Demkow, T. E. Hutson, M. Gore, S. Freeman, B. Schwartz, M. Shan, R. Simantov, R. M. Bukowski, et al., “Sorafenib in Advanced Clear-Cell Renal-Cell Carcinoma,” The New England Journal of Medicine, Vol. 356, No. 2, 2007, pp. 125-134. doi.:10.1056/NEJMoa060655
[8]	R. J. Motzer, T. E. Hutson, P. Tomczak, M. D. Michaelson, R. M. Bukowski, O. Rixe, S. Oudard, S. Negrier, C. Szczylik, S. T. Kim, I. Chen, P. W. Bycott, C. M. Baum and R. A. Figlin, “Sunitinib versus Interferon Alfa in Metastatic Renal-Cell Carcinoma,” The New England Journal of Medicine, Vol. 356, No. 2, 2007, pp. 115-124. doi:10.1056/NEJMoa065044
[9]	D. B. Mendel, A. D. Laird, X. Xin, S. G. Louie, J. G. Christensen, G. Li, R. E. Schreck, T. J. Abrams, T. J. Ngai, L. B. Lee, L. J. Murray, J. Carver, E. Chan, K. G. Moss, 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,” Clinical Cancer Research, Vol. 9, No. 1, 2003, pp. 327-337.
[10]	T. J. Abrams, L. B. Lee, L. J. Murray, N. K. Pryer and J. M. Cherrington, “SU11248 Inhibits KIT and Platelet- Derived Growth Factor Receptor Beta in Preclinical Models of Human Small Cell Lung Cancer,” Molecular Cancer Therapeutics, Vol. 2, No. 5, 2003, pp. 471-478.
[11]	R. J. Motzer, T. E. Hutson, P. Tomczak, M. D. Michaelson, R. M. Bukowski, S. Oudard, S. Negrier, C. Szczylik, R. Pili, G. A. Bjarnason, X. Garcia-del-Muro, J. A. Sosman, E. Solska, G. Wilding, J. A. Thompson, S. T. Kim, I. Chen, X. Huang and R. A. Figlin, “Overall Survival and Updated Results for Sunitinib Compared with Interferon Alfa in Patients with Renal Cell Carcinoma,” Journal of Clinical Oncology, Vol. 27, No. 22, 2009, pp. 3584-3590. doi:10.1200/JCO.2008.20.1293
[12]	C. Yoo, J. E. Kim, J. L. Lee, J. H. Ahn, D. H. Lee, J. S. Lee, S. Na, C. S. Kim, J. H. Hong, B. Hong, C. Song and H. Ahn, “The Efficacy and Safety of Sunitinib in Korean Patients with Advanced Renal Cell Carcinoma: High Incidence of Toxicity Leads to Frequent Dose Reduction,” Japanese Journal of Clinical Oncology, Vol. 40, No. 10, 2010, pp. 980-985. doi:10.1093/jjco/hyq073
[13]	H. Uemura, N. Shinohara, T. Yuasa, Y. Tomita, H. Fujimoto, M. Niwakawa, S. Mugiya, T. Miki, N. Nonomura, M. Takahashi, Y. Hasegawa, N. Agata, B. Houk, S. Naito and H. Akaza, “A Phase II Study of Sunitinib in Japanese Patients with Metastatic Renal Cell Carcinoma: Insight into the Treatment, Efficacy and Safety,” Japanese Journal of Clinical Oncology, Vol. 40, No. 3, 2010, pp. 194-202. doi:10.1093/jjco/hyp146
[14]	Y. Tomita, N. Shinohara, T. Yuasa, H. Fujimoto, M. Niwakawa, S. Mugiya, T. Miki, H. Uemura, N. Nonomura, M. Takahashi, Y. Hasegawa, N. Agata, B. Houk, S. Naito and H. Akaza, “Overall Survival and Updated Results from a Phase II Study of Sunitinib in Japanese Patients with Metastatic Renal Cell Carcinoma,” Japanese Journal of Clinical Oncology, Vol. 40, No. 12, 2010, pp. 1166-1172. doi:10.1093/jjco/hyq146
[15]	Y. Horikawa, N. Tsuchiya, K. Yuasa, S. Narita, M. Saito, K. Takayama, T. Nara, H. Tsuruta, T. Obara, K. Numakura, S. Satoh and T. Habuchi, “Efficacy and Safety of Sunitinib for Metastatic Renal Cell Carcinoma: Early Clinical Experiences at Akita University Hospital (Japan),” Japanese Journal of Clinical Oncology, Vol. 41, No. 3, 2011, pp. i6-i17. doi:10.1093/jjco/hyq254
[16]	R. J. Motzer, J. Bacik, L. H. Schwartz, V. Reuter, P. Russo, S. Marion and M. Mazumdar, “Prognostic Factors for Survival in Previously Treated Patients with Metastatic Renal Cell Carcinoma,” Journal of Clinical Oncology, Vol. 22, No. 3, 2004, pp. 454-463. doi:10.1200/JCO.2004.06.132
[17]	P. Therasse, S. G. Arbuck, E. A. Eisenhauer, J. Wanders, R. S. Kaplan, L. Rubinstein, J. Verweij, M. Van Glabbeke, A. T. van Oosterom, M. C. Christian and S. G. Gwyther, “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,” Journal of the National Cancer Institute, Vol. 92, No. 3, 2000, pp. 205-216. doi:10.1093/jnci/92.3.205
[18]	E. L. Kaplan and P. Meier, “Nonparametric Estimation from Incomplete Observations,” Journal of the American Statistical Association, Vol. 53, No. 282, 1958, pp. 457-481. doi:10.2307/2281868
[19]	T. Ueda, Y. Imamura, A. Komaru, S. Fukasawa, T. Sazuka, T. Suyama, Y. Naya, N. Nihei, T. Ichikawa and M. Maruoka, “Treatment Outcomes of Sorafenib for First Line or Cytokinerefractory Advanced Renal Cell Carcinoma in Japanese Patients,” International Journal of Urology, Vol. 17, No. 9, 2010, pp. 811-815.
[20]	G. Hudes, M. Carducci, P. Tomczak, J. Dutcher, R. Figlin, A. Kapoor, E. Staroslawska, J. Sosman, D. McDermott, I Bodrogi, Z. Kovacevic, V. Lesovoy, I. G. Schmidt-Wolf, O. Barbarash, E. Gokmen, T. O'Toole, S. Lustgarten, L. Moore, R. J. Motzer and Global ARCC Trial, “Temsirolimus, Interferon Alfa, or Both for Advanced Renal-Cell Carcinoma,” The New England Journal of Medicine, Vol. 356, No. 22, 2007, pp. 2271-2281. doi:10.1056/NEJMoa066838