title: Cediranib for metastatic alveolar soft part sarcoma.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. kummars@mail.nih.gov
authors: Shivaani
authors: S
authors: Kummar
authors: Deborah
authors: D
authors: Allen
authors: Anne
authors: A
authors: Monks
authors: Eric C
authors: EC
authors: Polley
authors: Curtis D
authors: CD
authors: Hose
authors: S Percy
authors: SP
authors: Ivy
authors: Ismail B
authors: IB
authors: Turkbey
authors: Scott
authors: S
authors: Lawrence
authors: Robert J
authors: RJ
authors: Kinders
authors: Peter
authors: P
authors: Choyke
authors: Richard
authors: R
authors: Simon
authors: Seth M
authors: SM
authors: Steinberg
authors: James H
authors: JH
authors: Doroshow
authors: Lee
authors: L
authors: Helman
mesh_terms: D000328:Adult; D000855:Anorexia / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D053263:Gene Regulatory Networks; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011446:Prospective Studies; D011799:Quinazolines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018234:Sarcoma, Alveolar Soft Part / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult; D007211:Indoles
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; C500926:cediranib; D007211:Indoles
references: Eur J Cancer. 2003 Jul;39(11):1511-6
references: 12855256
references: J Clin Oncol. 2009 Nov 20;27(33):5601-6
references: 19826113
references: Eur J Cancer. 2012 Mar;48(4):527-37
references: 22285180
references: Ann Oncol. 2011 Jul;22(7):1682-1690
references: 21242589
references: Nat Rev Cancer. 2012 Jan 24;12(2):89-103
references: 22270953
references: J Clin Oncol. 2007 Jul 20;25(21):3045-54
references: 17634482
references: Cancer. 2001 Feb 1;91(3):585-91
references: 11169942
references: Am J Pathol. 2001 Jul;159(1):179-92
references: 11438465
references: Cancer Res. 2007 Feb 1;67(3):919-29
references: 17283122
references: J Clin Oncol. 2010 Dec 10;28(35):5174-81
references: 21060028
references: Cancer. 2012 Dec 1;118(23):5894-902
references: 22605650
references: Cancer. 1989 Jan 1;63(1):1-13
references: 2642727
references: Oncogene. 2001 Jan 4;20(1):48-57
references: 11244503
references: Clin Cancer Res. 2007 Dec 15;13(24):7314-21
references: 18094412
references: Arch Pathol Lab Med. 2007 Mar;131(3):488-91
references: 17516754
references: Front Biosci (Landmark Ed). 2011 Jan 01;16:1172-85
references: 21196225
references: AJR Am J Roentgenol. 1989 Aug;153(2):335-9
references: 2750619
references: Mol Cancer Ther. 2007 Aug;6(8):2198-208
references: 17699717
references: Eur J Cancer. 2011 May;47(7):997-1005
references: 21247755
references: J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
references: 10655437
references: Cancer Res. 2005 May 15;65(10):4389-400
references: 15899831
references: BMC Cancer. 2009 Jan 15;9:22
references: 19146682
references: Cancer Discov. 2012 Mar;2(3):270-87
references: 22585997