A phase II clinical trial of polyethylene glycol-conjugated L-asparaginase in patients with advanced ovarian cancer: Early closure for safety

Hays,John  L.; Kim,Geoff; Walker,Amanda; Annunziata,Christina  M.; Lee,Jung-Min; Squires,Jennifer; Houston,Nicole; Steinberg,Seth  M.; Kohn,Elise  C.

doi:10.3892/mco.2013.99

May-June 2013 Volume 1 Issue 3

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May-June 2013 Volume 1 Issue 3

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Article

A phase II clinical trial of polyethylene glycol-conjugated L-asparaginase in patients with advanced ovarian cancer: Early closure for safety

Authors:
- John L. Hays
- Geoff Kim
- Amanda Walker
- Christina M. Annunziata
- Jung-Min Lee
- Jennifer Squires
- Nicole Houston
- Seth M. Steinberg
- Elise C. Kohn
View Affiliations / Copyright

Affiliations: Women's Cancers Clinic, Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA, Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, Rockville, MD 20852, USA
Pages: 565-569
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Published online on: March 20, 2013

https://doi.org/10.3892/mco.2013.99
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Abstract

The anti-angiogenic activity of L‑asparaginase (L‑ASP) and the sensitivity of ovarian cancer cell lines to L‑ASP has been previously demonstrated by preclinical findings. The aim of this clinical trial was to translate those findings and evaluate the activity of polyethylene glycol‑conjugated L‑asparaginase (PEG-ASP or pegaspargase) in advanced ovarian cancer. Women with recurrent ovarian cancer and good end‑organ function were enrolled in an open‑label phase II trial of PEG-ASP at a dose of 2,000 IU/m2 by intravenous infusion every 2 weeks. Patients were evaluated for response every 8 weeks and for toxicity on an ongoing basis. Early stopping rules for toxicity and activity were included. Four patients were enrolled and received a total of 7 treatment cycles. The study ended accrual by invoking an early stopping rule, after excessive toxicity was identified in patients. Drug-related toxicities included grade 2 pancreatitis, fatigue, neutropenia, hypoalbuminemia, weight loss, dehydration, decreased fibrinogen and 1 case of grade 3 hypersensitivity reaction during cycle 2. One patient died during the study. No patients were evaluable for response. PEG-ASP was poorly tolerated in this group of advanced‑stage ovarian cancer patients and no conclusions regarding activity may be drawn. Further studies of PEG-ASP in ovarian cancer patients are not recommended.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

A phase II clinical trial of polyethylene glycol-conjugated L-asparaginase in patients with advanced ovarian cancer: Early closure for safety

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