title: A phase II study of a urokinase-derived peptide (A6) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma: a Gynecologic Oncology Group study.
abstract: OBJECTIVE
  This multi-institutional phase II trial assessed the activity and tolerability of the anti-metastatic A6 peptide that binds CD44 in patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (EOC/FTC/PPC).
  
  
  METHODS
  Women with persistent or recurrent EOC/FTC/PPC were eligible for participation if they had measurable disease defined by RECIST criteria, good performance status, and good overall organ function. Patients must have received one prior platinum-based chemotherapeutic regimen and were allowed to have received one additional cytotoxic regimen for the management of recurrent or persistent disease. Women received a 150 mg twice daily subcutaneous dose of A6 and continued on treatment until disease progression or unacceptable toxicity. Primary measures of clinical efficacy were objective tumor response and progression-free survival (PFS) at 6 months. The association of CD44 in archival tissue specimens with clinical outcome was investigated.
  
  
  RESULTS
  Thirty-one eligible patients were evaluated. No responses were observed. Two patients (6.5%) were progression free for at least 6 months. The median PFS was 2.0 months, and median overall survival has not yet been reached. One patient died of hemorrhage which was possibly study related. There were no grade 4 toxicities. The most common grade 3 toxicities were constitutional (2/31; 6.5%). Archival specimens were available for 27 patients, and 5 (18.5%) were CD44 positive by immunohistochemistry. CD44 expression was not associated with the 6-month PFS (p=0.342).
  
  
  CONCLUSIONS
  A6 was well tolerated but had minimal activity in patients with persistent or recurrent EOC/FTC/PPC.
authors.affiliation: Vanderbilt University Medical Center, B1100 Medical Center North, 1161 21st Avenue South, Nashville, TN 37232, USA. michael.gold@vanderbilt.edu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gold
authors.forename: William E
authors.initials: WE
authors.lastname: Brady
authors.forename: Heather A
authors.initials: HA
authors.lastname: Lankes
authors.forename: Peter G
authors.initials: PG
authors.lastname: Rose
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Kelley
authors.forename: Koen
authors.initials: K
authors.lastname: De Geest
authors.forename: Marta A
authors.initials: MA
authors.lastname: Crispens
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Resnick
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Howell
mesh_terms: D000328:Adult; D000368:Aged; D000077216:Carcinoma, Ovarian Epithelial; D018572:Disease-Free Survival; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010446:Peptide Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D010446:Peptide Fragments; D014568:Urokinase-Type Plasminogen Activator; C489333:acetyl-lysyl-prolyl-seryl-seryl-prolyl-prolyl-glutamyl-glutamic acid amide