A Phase II Study of Sunitinib in Japanese Patients with Metastatic Renal Cell Carcinoma: Insights into the Treatment, Efficacy and Safety

Uemura, Hirotsugu; Shinohara, Nobuo; Yuasa, Takeshi; Tomita, Yoshihiko; Fujimoto, Hiroyuki; Niwakawa, Masashi; Mugiya, Soichi; Miki, Tsuneharu; Nonomura, Norio; Takahashi, Masayuki; Hasegawa, Yoshihiro; Agata, Naoki; Houk, Brett E.; Naito, Seiji; Akaza, Hideyuki

doi:10.1093/jjco/hyp146

Cited by 132 publications

(98 citation statements)

References 21 publications

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“…Compared to the Caucasian population, Asian people in general have a relatively lower body surface area (BSA), and as a result drug exposure in Asian patients may be higher after a standard dose. However, no or only a relatively small effect of BSA on sunitinib pharmacokinetics was identified in both Caucasian [44] and Japanese patients [46]. In contrast, the lean body mass (LBM) has recently been identified to be related with sunitinib and SU12662 exposure in 92 patients with solid tumors.…”

Section: Discussionmentioning

confidence: 99%

Assessment of ethnic differences in sunitinib outcome between Caucasian and Asian patients with metastatic renal cell carcinoma: a meta-analysis

et al. 2016

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Background: An increasing number of studies have reported ethnic differences in sunitinib outcome in metastatic renal cell carcinoma (mRCC) patients. However, a comprehensive analysis is still lacking. Therefore, we systematically collected available published data and performed a meta-analysis to compare sunitinib efficacy and toxicity in Asian and Caucasian mRCC patients. Methods: Data were extracted from published results from clinical trials, expanded access program and real-world clinical practice. Progression-free survival (or time to tumor progression), overall survival, objective response rate and adverse events were used as endpoints to evaluate the differences of sunitinib outcome between the two ethnicities. For adverse events, we focused the following clinically relevant side effects: diarrhea, fatigue, mucositis/stomatitis, hand-foot syndrome, hypertension, leukopenia, neutropenia and thrombocytopenia. Results: A total of 33 publications including 9977 patients were available for meta-analysis. The efficacy of sunitinib in Asian patients was similar to that in Caucasian patients. However, Asian patients showed a higher incidence of all grades toxicity of hand-foot syndrome, > grade 2 fatigue, > grade 2 hand-foot syndrome and > grade 2 thrombocytopenia. Conclusion: Ethnic differences in adverse events of sunitinib in mRCC patients existed and dose adjustment in Asian patients may be considered.

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Section: Discussionmentioning

confidence: 99%

Assessment of ethnic differences in sunitinib outcome between Caucasian and Asian patients with metastatic renal cell carcinoma: a meta-analysis

et al. 2016

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“…Sunitinib is widely used for the treatment of advanced renal cell carcinoma and imatinib-refractory gastrointestinal stromal tumors, and was recently approved for pancreatic neuroendocrine tumors by the U. S. Food and Drug Administration and European Medicines Agency. Several clinical trials have demonstrated that sunitinib significantly improves overall survival as well as progression-free survival in patients with advanced renal cell carcinoma (Motzer et al, 2007(Motzer et al, , 2009) and imatinib-refractory gastrointestinal stromal tumors (Demetri et al, 2006); however, patients taking sunitinib are often forced to reduce the dose or discontinue treatment because of frequent adverse events, such as thrombocytopenia, liver dysfunction, and hand-foot syndrome (Demetri et al, 2006;Motzer et al, 2007Motzer et al, , 2009Hong et al, 2009;Uemura et al, 2010;Yoo et al, 2010). In addition, tumor regrowth observed during drug-off periods is recognized as a serious problem (Chow and Eckhardt, 2007).…”

Section: Introductionmentioning

confidence: 99%

Effect of P-Glycoprotein and Breast Cancer Resistance Protein Inhibition on the Pharmacokinetics of Sunitinib in Rats

et al. 2013

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The aim of this study was to elucidate the roles of P-glycoprotein (P-gp/ABCB1) and breast cancer resistance protein (BCRP/ABCG2) in the plasma concentration, biliary excretion, and distribution to the liver, kidney, and brain of sunitinib. The pharmacokinetics of sunitinib was examined in rats treated with PSC833 (valspodar) and pantoprazole, potent inhibitors of P-gp and BCRP, respectively. The sunitinib concentrations in plasma, bile, liver, kidney, and brain were determined by liquid chromatography-tandem mass spectrometry. It was found that the area under the concentration-time curve for 4 hours (AUC 0-4 ) and maximum concentration (C max ) of sunitinib administered intraintestinally were significantly increased by pretreatment with PSC833 or pantoprazole. Each inhibitor markedly reduced the biliary excretion of sunitinib for 60 minutes after an intravenous administration and significantly increased the distribution of sunitinib to the liver as well as kidney. In addition, the brain distribution of sunitinib was significantly increased by PSC833 but not pantoprazole, and coadministration of both inhibitors further enhanced the accumulation of sunitinib in the brain. These results demonstrate that plasma concentrations of sunitinib and the biliary excretion and distribution to the kidney, liver, and brain of sunitinib are influenced by pharmacologic inhibition of P-gp and/or BCRP.

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“…Hypothyroidism was also considered to be an important AE associated with sunitinib treatment, for which 31 patients (53.4%) required medication during this study. ficacy and safety of these agents in the Western world [7,8,11], only few reports have described findings in Asian populations [12][13][14]19]. In 2010, Tomita et al reported updated results from a Phase II trial of sunitinib in the Japanese population [14].…”

Section: Evaluation Of Aesmentioning

confidence: 99%

“…In addition, only patients with clear-cell histology were eligible for the study [8]. Although sunitinib has been universally prescribed to patients with mRCC, few studies have examined the efficacy and safety of this agent in daily clinical practice, especially in patients of Asian ethnicity [12][13][14][15]. Here, we assessed the efficacy and safety of sunitinib in Japanese patients with mRCC in general clinical practice.…”

Section: Introductionmentioning

confidence: 99%

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

Suyama¹,

Ueda²,

Fukasawa³

et al. 2011

JCT

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A Phase II Study of Sunitinib in Japanese Patients with Metastatic Renal Cell Carcinoma: Insights into the Treatment, Efficacy and Safety

Abstract: In Japanese patients with RCC, sunitinib is consistently effective and tolerable with similar risk/benefit as that in Western patients, though there was a trend toward greater antitumour efficacy and higher incidence of haematological adverse events in Japanese patients.

Cited by 132 publications

References 21 publications

Assessment of ethnic differences in sunitinib outcome between Caucasian and Asian patients with metastatic renal cell carcinoma: a meta-analysis

Assessment of ethnic differences in sunitinib outcome between Caucasian and Asian patients with metastatic renal cell carcinoma: a meta-analysis

Effect of P-Glycoprotein and Breast Cancer Resistance Protein Inhibition on the Pharmacokinetics of Sunitinib in Rats

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

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