Cediranib for metastatic alveolar soft part sarcoma.
J Clin Oncol, 2013/6/20;31(18):2296-302.
Kummar S[1], Allen D, Monks A, Polley EC, Hose CD, Ivy SP, Turkbey IB, Lawrence S, Kinders RJ, Choyke P, Simon R, Steinberg SM, Doroshow JH, Helman L
Affiliations
PMID: 23630200DOI: 10.1200/JCO.2012.47.4288
Impact factor: 50.717
Abstract
purpose: Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor, for which no effective standard systemic treatment exists for patients with unresectable disease. Cediranib is a potent, oral small-molecule inhibitor of all three vascular endothelial growth factor receptors (VEGFRs).
patients and methods: We conducted a phase II trial of once-daily cediranib (30 mg) given in 28-day cycles for patients with metastatic, unresectable ASPS to determine the objective response rate (ORR). We also compared gene expression profiles in pre- and post-treatment tumor biopsies and evaluated the effect of cediranib on tumor proliferation and angiogenesis using positron emission tomography and dynamic contrast-enhanced magnetic resonance imaging.
results: Of 46 patients enrolled, 43 were evaluable for response at the time of analysis. The ORR was 35%, with 15 of 43 patients achieving a partial response. Twenty-six patients (60%) had stable disease as the best response, with a disease control rate (partial response + stable disease) at 24 weeks of 84%. Microarray analysis with validation by quantitative real-time polymerase chain reaction on paired tumor biopsies from eight patients demonstrated downregulation of genes related to vasculogenesis.
conclusion: In this largest prospective trial to date of systemic therapy for metastatic ASPS, we observed that cediranib has substantial single-agent activity, producing an ORR of 35% and a disease control rate of 84% at 24 weeks. On the basis of these results, an open-label, multicenter, randomized phase II registration trial is currently being conducted for patients with metastatic ASPS comparing cediranib with another VEGFR inhibitor, sunitinib.
MeSH terms
Adult; Anorexia; Antineoplastic Agents; Diarrhea; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Hypertension; Male; Middle Aged; Oligonucleotide Array Sequence Analysis; Prospective Studies; Quinazolines; Reverse Transcriptase Polymerase Chain Reaction; Sarcoma, Alveolar Soft Part; Treatment Outcome; Young Adult
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