FCCC LOGO Faculty Publications
Rixe O , Bukowski RM , Michaelson MD , Wilding G , Hudes GR , Bolte O , Motzer RJ , Bycott P , Liou KF , Freddo J , Trask PC , Kim S , Rini BI
Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study
Lancet Oncology. 2007 Nov;8(11) :975-984
PMID: ISI:000250907300017   
Back to previous list
Background Axitinib (AG-013736) is an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3. We aimed to assess the activity and safety of axitinib in patients with metastatic renal-cell cancer who had failed on previous cytokine-based treatment. Methods Between Oct 3, 2003, and April 7, 2004, 52 patients were enrolled. All patients who had at least one measurable target lesion received axitinib orally (starting dose 5 mg twice daily). The primary endpoint was objective response (ie, percentage of patients with confirmed complete response or partial response by use of Response Evaluation Criteria In Solid Tumors [RECIST] criteria. Secondary endpoints were duration of response, time to progression, overall survival, safety, pharmacokinetics, and patient-reported health-related quality of life. This trial is registered on the clinical trials site of the US National Cancer Institute website http://www.clinicaltrials.gov/ct/show/ NCT00076011. Findings In an intention-to-treat analysis, two complete and 21 partial responses were noted, for an objective response rate of 44.2% (95% CI 30.5-58.7). Median response duration was 23.0 months (20.9-not estimable; range 4.2-29.8). However, 12 of 23 initial responders progressed with response duration ranging from 4.2 months to 26.5 months. Additionally, 22 patients showed stable disease for longer than 8 weeks, including 13 patients with stable disease for 24 weeks or longer. Four patients had early disease progression. Three patients had missing response data. Median time to progression was 15.7 months (8.4-23.4, range 0.03-31.5) and median overall survival was 29.9 months (20.3-not estimable; range 2.4-35.8). Treatment-related adverse events included diarrhoea, hypertension, fatigue, nausea, and hoarseness. Treatment-related hypertension occurred in 30 patients and resolved with antihypertensive treatment in all but eight patients, of whom seven patients had a history of hypertension at baseline. Interpretation Axitinib shows clinical activity in patients with cytokine-refractory metastatic renal-cell cancer. Although 28 patients had grade 3 or grade 4 treatment-related adverse events, these adverse events were generally manageable and controlled by dose modification or supportive care, or both. Further studies are needed to confirm these findings.
ISI Document Delivery No.: 230WP Times Cited: 2 Cited Reference Count: 18 Cited References: AARONSON NK, 1993, J NATL CANCER I, V85, P365 ESCUDIER B, 2007, J CLIN ONCOL, V25, S2 ESCUDIER B, 2007, NEW ENGL J MED, V356, P125 JEMAL A, 2006, CA-CANCER J CLIN, V56, P106 KUENEN BC, 2003, CLIN CANCER RES, V9, P1648 MANCUSO MR, 2006, J CLIN INVEST, V116, P2610 MOTZER RJ, 2000, J CLIN ONCOL, V18, P1928 MOTZER RJ, 2004, J CLIN ONCOL, V22, P454 MOTZER RJ, 2006, J CLIN ONCOL, V24, P16 MOTZER RJ, 2007, NEW ENGL J MED, V356, P115 NEGRIER S, 2005, J CLIN ONCOL S 1, V23, S380 OSOBA D, 1998, J CLIN ONCOL, V16, P139 RINI BI, 2005, J CLIN ONCOL, V23, P1028 RUGO HS, 2005, J CLIN ONCOL, V23, P5474 SUGIMOTO H, 2003, J BIOL CHEM, V278, P12605 TAM BYY, 2006, NAT MED, V12, P793 THERASSE P, 2000, J NATL CANCER I, V92, P205 YANG JC, 2003, NEW ENGL J MED, V349, P427 Rixe, Olivier Bukowski, Ronald M. Michaelson, M. Dror Wilding, George Hudes, Gaty R. Bolte, Oliver Motzer, Robert J. Bycott, Paul Liou, Katherine F. Freddo, James Trask, Peter C. Kim, Sinil Rini, Brian I. LANCET LTD; 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND