Abstract | PURPOSE: 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). PATIENTS AND 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). CONCLUSION: A6 was well tolerated but had minimal activity in patients with persistent or recurrent EOC/ FTC/PPC.
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Authors | Michael A Gold, William E Brady, Heather A Lankes, Peter G Rose, Joseph L Kelley, Koen De Geest, Marta A Crispens, Kimberly E Resnick, Stephen B Howell |
Journal | Gynecologic oncology
(Gynecol Oncol)
Vol. 125
Issue 3
Pg. 635-9
(Jun 2012)
ISSN: 1095-6859 [Electronic] United States |
PMID | 22446624
(Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Elsevier Inc. All rights reserved. |
Chemical References |
- CD44 protein, human
- Hyaluronan Receptors
- Peptide Fragments
- Urokinase-Type Plasminogen Activator
- acetyl-lysyl-prolyl-seryl-seryl-prolyl-prolyl-glutamyl-glutamic acid amide
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Topics |
- Adult
- Aged
- Carcinoma, Ovarian Epithelial
- Disease-Free Survival
- Fallopian Tube Neoplasms
(drug therapy, metabolism)
- Female
- Humans
- Hyaluronan Receptors
(biosynthesis)
- Middle Aged
- Neoplasm Recurrence, Local
(drug therapy)
- Neoplasms, Glandular and Epithelial
(drug therapy, metabolism)
- Ovarian Neoplasms
(drug therapy, metabolism)
- Peptide Fragments
(adverse effects, therapeutic use)
- Peritoneal Neoplasms
(drug therapy, metabolism)
- Urokinase-Type Plasminogen Activator
(adverse effects, therapeutic use)
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