TY - JOUR
T1 - Individualized Dosing of Axitinib Based on First-Dose Area Under the Concentration–Time Curve for Metastatic Renal-Cell Carcinoma
AU - Miura, Yuji
AU - Imamura, Chiyo K.
AU - Uchino, Keita
AU - Kishida, Takeshi
AU - Matsubara, Nobuaki
AU - Shinojima, Toshiaki
AU - Kondo, Keiichi
AU - Hongo, Fumiya
AU - Yoshimura, Kenichi
AU - Tanigawara, Yusuke
AU - Takano, Toshimi
PY - 2019/2
Y1 - 2019/2
N2 - 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.
AB - 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.
KW - First-dose AUC
KW - Kidney cancer
KW - Recommended dose
KW - VEGFR inhibitor
KW - mRCC
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U2 - 10.1016/j.clgc.2018.09.015
DO - 10.1016/j.clgc.2018.09.015
M3 - Article
C2 - 30529389
AN - SCOPUS:85055275886
VL - 17
SP - e1-e11
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
SN - 1558-7673
IS - 1
ER -