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

Abstract 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 (AUC 0-12 ) 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 AUC 0-12 . On day 15 of axitinib administration, the dose was adjusted to ensure ≥ 150 ng·h/mL AUC 0-12 at steady state according to first-dose AUC 0-12 . 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 AUC 0-12 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 AUC 0-12 might have promising efficacy and manageable toxicity.