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 (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. Individualized dosing of axitinib based on drug exposure remains unknown. In this study we evaluated the efficacy and safety of the recommended axitinib dose on the basis of the first-dose area under the concentration–time curve from 0 to 12 hours in metastatic renal-cell carcinoma. Adjusting to the recommended dose lead to promising efficacy and manageable toxicity. The current study provides novel information to develop individualized axitinib treatment.
| Original language | English |
|---|---|
| Journal | Clinical Genitourinary Cancer |
| DOIs | |
| Publication status | Accepted/In press - 2018 Jan 1 |
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Keywords
- First-dose AUC
- Kidney cancer
- mRCC
- Recommended dose
- VEGFR inhibitor
ASJC Scopus subject areas
- Oncology
- Urology
Cite this
Individualized Dosing of Axitinib Based on First-Dose Area Under the Concentration–Time Curve for Metastatic Renal-Cell Carcinoma. / Miura, Yuji; Imamura, Chiyo; Uchino, Keita; Kishida, Takeshi; Matsubara, Nobuaki; Shinojima, Toshiaki; Kondo, Keiichi; Hongo, Fumiya; Yoshimura, Kenichi; Tanigawara, Yusuke; Takano, Toshimi.
In: Clinical Genitourinary Cancer, 01.01.2018.Research output: Contribution to journal › Article
}
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
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 - 2018/1/1
Y1 - 2018/1/1
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. Individualized dosing of axitinib based on drug exposure remains unknown. In this study we evaluated the efficacy and safety of the recommended axitinib dose on the basis of the first-dose area under the concentration–time curve from 0 to 12 hours in metastatic renal-cell carcinoma. Adjusting to the recommended dose lead to promising efficacy and manageable toxicity. The current study provides novel information to develop individualized axitinib treatment.
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. Individualized dosing of axitinib based on drug exposure remains unknown. In this study we evaluated the efficacy and safety of the recommended axitinib dose on the basis of the first-dose area under the concentration–time curve from 0 to 12 hours in metastatic renal-cell carcinoma. Adjusting to the recommended dose lead to promising efficacy and manageable toxicity. The current study provides novel information to develop individualized axitinib treatment.
KW - First-dose AUC
KW - Kidney cancer
KW - mRCC
KW - Recommended dose
KW - VEGFR inhibitor
UR - http://www.scopus.com/inward/record.url?scp=85055275886&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055275886&partnerID=8YFLogxK
U2 - 10.1016/j.clgc.2018.09.015
DO - 10.1016/j.clgc.2018.09.015
M3 - Article
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
SN - 1558-7673
ER -