title: Overall survival and final efficacy and safety results from a Japanese phase II study of axitinib in cytokine-refractory metastatic renal cell carcinoma.
abstract: In an open-label, multicenter phase II study of Japanese patients with cytokine-refractory metastatic renal cell carcinoma, axitinib showed substantial antitumor activity with an acceptable safety profile. Here, we report overall survival and updated efficacy and safety results. Sixty-four Japanese patients with metastatic renal cell carcinoma following prior therapy with cytokines were treated with axitinib at a starting dose of 5 mg b.i.d. Following median treatment duration of 14.2 months, median overall survival was 37.3 months (95% CI, 28.6-49.9). The objective response rate, the primary endpoint of the study, was 51.6% (95% CI, 38.7-64.2); the median duration of response, 11.1 months (95% CI, 8.2-13.7); and the median progression-free survival was 11.0 months (95% CI, 9.2-12.0), assessed by the independent review committee. Common treatment-related all-grade adverse events were hypertension (88%), hand-foot syndrome (75%), diarrhea (66%), proteinuria (63%), fatigue (55%) and dysphonia (53%). In an exploratory analysis, median overall survival was found to be significantly longer in patients who had greater decreases in plasma levels of soluble vascular endothelial growth factor receptor-2 during the first cycle of treatment. In conclusion, the present study showed axitinib to be effective, and toxicities with long-term treatment were generally controllable with axitinib dose modification and/or standard medications in these Japanese patients. Some frequently reported adverse events warrant close monitoring and management. Changes in the plasma levels of soluble vascular endothelial growth factor receptor-2 may be used as a prognostic factor for overall survival in metastatic renal cell carcinoma following axitinib treatment. This study is registered at ClinicalTrial.gov (identifier NCT00569946).
authors.affiliation: Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Eto
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Uemura
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Tomita
authors.forename: Hiroomi
authors.initials: H
authors.lastname: Kanayama
authors.forename: Nobuo
authors.initials: N
authors.lastname: Shinohara
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kamei
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Fujii
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Umeyama
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Ozono
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Akaza
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000077784:Axitinib; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects*; D007191:Indazoles / Q000008:administration & dosage / Q000009:adverse effects*; D007564:Japan; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000473:pathology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D007191:Indazoles; D000077784:Axitinib; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Axitinib; Japanese; cytokine-refractory; overall survival; renal cell carcinoma