Work

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

Year: 2013

Type: article

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.

Source: Molecular and Clinical Oncology

DOI: 10.3892/mco.2013.99