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J Clin Oncol. 2013 Jun 20;31(18):2296-302. doi: 10.1200/JCO.2012.47.4288. Epub 2013 Apr 29.

Cediranib for metastatic alveolar soft part sarcoma.

Author information

1
National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. kummars@mail.nih.gov

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00942877.

PMID:
23630200
PMCID:
PMC3677840
DOI:
10.1200/JCO.2012.47.4288
[Indexed for MEDLINE]
Free PMC Article

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