Assessment of Sunitinib-Induced Toxicities and Clinical Outcomes Based on Therapeutic Drug Monitoring of Sunitinib for Patients With Renal Cell Carcinoma

作者：Noda Satoshi; Otsuji Takashi; Baba Masato; Yoshida Tetsuya; Kageyama Susumu; Okamoto Keisei; Okada Yusaku; Kawauchi Akihiro; Onishi Hiroyuki; Hira Daiki; Morita Shin ya; Terada Tomohiro^*

来源：Clinical Genitourinary Cancer, 2015, 13(4): 350-358.

DOI：10.1016/j.clgc.2015.01.007

• Individualized pharmacotherpy
• Kidney cancer
• Pharmacokinetics
• Tolerability
• Tyrosine kinase inhibitor

The benefit of pharmacokinetic assessment of sunitinib remains unknown. We reported that patients with total sunitinib (sunitinib + its active metabolite SU12662) >= 100 ng/mL showed high incidence of Grade >= 3 toxicities and worsening clinical outcomes. Thus, pharmacokinetic assessment of sunitinib could be helpful for dose optimization.
Background: Sunitinib has been approved for the treatment of metastatic renal cell carcinoma (RCC). Sunitinib pharmacokinetics shows a large interpatient variability. Patients and Methods: A retrospective, observational clinical study of 21 patients with RCC was performed. Sunitinib was administered for 4 weeks of a 6-week cycle for the first cycle. We evaluated the association of sunitinib-induced toxicities and clinical outcomes with the trough total sunitinib concentration in a steady state during the first cycle. Results: The median total sunitinib concentration was 91.8 ng/mL (range, 49.8-205 ng/mL). There was an association between total sunitinib concentration and the severity of thrombocytopenia, anorexia, and fatigue. Patients with >= 100 ng/mL total sunitinib (n = 8), compared with patients with < 100 ng/mL (n = 13), had a greater incidence of Grade >= 3 toxicities (6 patients [75.0%] vs. 3 patients [23.1%]). Patients with < 100 ng/mL total sunitinib had significantly longer time to treatment failure (TTF) and progression-free survival (PFS) time than patients with >= 100 ng/mL (median TTF, 590 vs. 71 days; P = .04; median PFS, 748 vs. 238 days; P = .02). Conclusion: Results of this study suggest that therapeutic drug monitoring of sunitinib could be useful for avoiding severe toxicities. Dose reduction might be needed, especially when the total sunitinib concentration is >= 100 ng/mL, to avoid unnecessary early discontinuation of treatment.

• 出版日期2015-8