title: A phase II clinical trial of polyethylene glycol-conjugated L-asparaginase in patients with advanced ovarian cancer: Early closure for safety.
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/m2by 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.
authors.affiliation: Women's Cancers Clinic, Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892;
authors.forename: John L
authors.initials: JL
authors.lastname: Hays
authors.affiliation: Women's Cancers Clinic, Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892;
authors.forename: Geoff
authors.initials: G
authors.lastname: Kim
authors.affiliation: Women's Cancers Clinic, Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892;
authors.forename: Amanda
authors.initials: A
authors.lastname: Walker
authors.affiliation: Women's Cancers Clinic, Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892;
authors.forename: Christina M
authors.initials: CM
authors.lastname: Annunziata
authors.affiliation: Women's Cancers Clinic, Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892;
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Women's Cancers Clinic, Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892;
authors.forename: Jennifer
authors.initials: J
authors.lastname: Squires
authors.affiliation: Women's Cancers Clinic, Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892;
authors.forename: Nicole
authors.initials: N
authors.lastname: Houston
authors.affiliation: Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, Rockville, MD 20852, USA.
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.affiliation: Women's Cancers Clinic, Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892;
authors.forename: Elise C
authors.initials: EC
authors.lastname: Kohn
keywords: L-asparaginase; angiogenesis; ovarian cancer; pegaspargase