Department of Urology, Yamagata University Faculty of Medicine, Yamagata, Japan.
Axitinib (AG-013736) is an oral, selective and potent inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, 2 and 3. This phase II study investigated axitinib efficacy, safety and biomarkers in Japanese patients with cytokine-refractory metastatic renal cell carcinoma (mRCC).
In an open-label, multicentre study, 64 patients received an axitinib starting dose of 5mg twice daily.
Objective response rate (ORR) was 50.0% and median progression-free survival (PFS) was 11.0months per independent review committee. Common treatment-related adverse events were hypertension (84%; 70% grade ⩾3), hand-foot syndrome (75%; 22% grade ⩾3) and diarrhoea (64%; 5% grade ⩾3). Eighteen patients (28%) developed proteinuria ⩾2g/24h and required dose reduction or treatment interruption/discontinuation. Proteinuria was a major cause for treatment discontinuation. Baseline urine protein levels were associated with development of proteinuria ⩾2g/24h (hazard ratio [HR]=5.457, P=0.0035 in patients with baseline proteinuria ⩾1+ versus < 1+). Baseline urine protein levels correlated more strongly with axitinib-related proteinuria than other baseline renal function test values or blood pressure. Patients with greater decreases in soluble VEGFR-2 concentrations had significantly higher ORR and longer PFS than those with smaller decreases (ORR: 64.5% versus 37.5%, P=0.045; median PFS: 12.9months versus 9.2months, HR=0.42, P=0.01).
Axitinib showed significant antitumour activity and was well tolerated in Japanese mRCC patients. Baseline proteinuria and soluble VEGFR-2 levels may be key indicators of axitinib-induced proteinuria and efficacy, respectively.
Written by:
Tomita Y, Uemura H, Fujimoto H, Kanayama HO, Shinohara N, Nakazawa H, Imai K, Umeyama Y, Ozono S, Naito S, Akaza H. Are you the author?
Reference: Eur J Cancer. 2011 Aug 31. Epub ahead of print.
doi: 10.1016/j.ejca.2011.07.014
PubMed Abstract
PMID: 21889330
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