Individualized Dosing of Axitinib Based on First-Dose Area Under the Concentration–Time Curve for Metastatic Renal-Cell Carcinoma

Yuji Miura, Chiyo K. Imamura, Keita Uchino, Takeshi Kishida, Nobuaki Matsubara, Toshiaki Shinojima, Keiichi Kondo, Fumiya Hongo, Kenichi Yoshimura, Yusuke Tanigawara, Toshimi Takano

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6 Citations (Scopus)


Background: Previous studies have revealed that higher exposure of axitinib leads to better prognosis in metastatic renal-cell carcinoma. We thus assessed individualized dosing of axitinib on the basis of the first-dose area under the concentration–time curve from 0 to 12 hours (AUC0-12) for sunitinib-pretreated metastatic renal-cell carcinoma patients. Patients and Methods: In this prospective single-arm trial, the starting dose of axitinib was 5 mg twice daily. A series of blood samples were taken at predetermined times after the first dose to calculate AUC0-12. On day 15 of axitinib administration, the dose was adjusted to ensure ≥ 150 ng·h/mL AUC0-12 at steady state according to first-dose AUC0-12. The primary end point was the 6-month progression-free survival rate. Results: Twenty-six Japanese patients were enrolled. The median recommended dose based on the first-dose AUC0-12 was 2.5 mg (range, 1-16 mg) twice daily. The 6-month progression-free survival rate for all enrolled patients and per-protocol set, from which 3 patients were excluded for not adjusting to the recommended dose on day 15, was 84.6% (95% confidence interval, 65.5-94.1) and 82.6% (95% confidence interval, 61.8-93.3), respectively. The most common nonhematologic adverse events were hypertension, hand–foot syndrome, fatigue, and decreased appetite. Eighteen patients (75%) developed grade 3 hypertension; however, actual blood pressure could be controlled using antihypertensive agents. Other adverse events were manageable during the protocol treatment. Conclusion: Individualized dosing of axitinib based on the first-dose AUC0-12 might have promising efficacy and manageable toxicity.

Original languageEnglish
Pages (from-to)e1-e11
JournalClinical Genitourinary Cancer
Issue number1
Publication statusPublished - 2019 Feb


  • First-dose AUC
  • Kidney cancer
  • Recommended dose
  • VEGFR inhibitor
  • mRCC

ASJC Scopus subject areas

  • Oncology
  • Urology


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