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

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

13 ( 4 )  , pp.350 - 358 , 2015-08 , Elsevier
Description
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.
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.
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http://repository.shiga-med.ac.jp/dspace//bitstream/10422/10933/1/j.clgc.2015.01.007.pdf

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