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

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.

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.

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.

Individualized dosing of axitinib based on the first-dose AUC0-12 might have promising efficacy and manageable toxicity.

Clinical genitourinary cancer. 2018 Sep 29 [Epub ahead of print]

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

Department of Medical Oncology, Toranomon Hospital, Tokyo, Japan. Electronic address: ., Department of Clinical Pharmacokinetics and Pharmacodynamics, Keio University School of Medicine, Tokyo, Japan., Department of Medical Oncology, Kyusyu Medical Center, Fukuoka, Japan., Department of Urology, Kanagawa Cancer Center Hospital, Kanagawa, Japan., Department of Breast and Medical Oncology, National Cancer Center Hospital East, Chiba, Japan., Department of Urology, Keio University School of Medicine, Tokyo, Japan., Department of Urology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan., Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan., Innovative Clinical Research Center, Kanazawa University Hospital, Ishikawa, Japan., Department of Medical Oncology, Toranomon Hospital, Tokyo, Japan.

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