title: Assessment of Sunitinib-Induced Toxicities and Clinical Outcomes Based on Therapeutic Drug Monitoring of Sunitinib for Patients With Renal Cell Carcinoma.
abstract: BACKGROUND
  Sunitinib has been approved for the treatment of metastatic renal cell carcinoma (RCC). Sunitinib pharmacokinetics shows a large interpatient variability.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacy, Shiga University of Medical Science Hospital, Shiga, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Noda
authors.affiliation: Department of Pharmacy, Shiga Medical Center for Adults, Shiga, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Otsuji
authors.affiliation: Department of Urology, Shiga University of Medical Science Hospital, Shiga, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Baba
authors.affiliation: Department of Urology, Shiga University of Medical Science Hospital, Shiga, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of Urology, Shiga University of Medical Science Hospital, Shiga, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Kageyama
authors.affiliation: Department of Urology, Shiga University of Medical Science Hospital, Shiga, Japan.
authors.forename: Keisei
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Department of Urology, Shiga University of Medical Science Hospital, Shiga, Japan.
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Department of Urology, Shiga University of Medical Science Hospital, Shiga, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kawauchi
authors.affiliation: Department of Urology, Shiga Medical Center for Adults, Shiga, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Onishi
authors.affiliation: Department of Pharmacy, Shiga University of Medical Science Hospital, Shiga, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Hira
authors.affiliation: Department of Pharmacy, Shiga University of Medical Science Hospital, Shiga, Japan.
authors.forename: Shin-Ya
authors.initials: SY
authors.lastname: Morita
authors.affiliation: Department of Pharmacy, Shiga University of Medical Science Hospital, Shiga, Japan. Electronic address: teradat@belle.shiga-med.ac.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Terada
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007211:Indoles / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011758:Pyrroles / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D012189:Retrospective Studies; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
keywords: Individualized pharmacotherpy; Kidney cancer; Pharmacokinetics; Tolerability; Tyrosine kinase inhibitor