Randomized trial of two intravenous schedules of the topoisomerase I inhibitor liposomal lurtotecan in women with relapsed epithelial ovarian cancer: a trial of the national cancer institute of Canada clinical trials group.
Authors
Dark, Graham GCalvert, A Hilary
Grimshaw, Robert
Poole, Christopher
Swenerton, Ken
Kaye, Stan B
Coleman, Robert E
Jayson, Gordon C
Le, Tien
Ellard, Susan
Trudeau, Marc
Vasey, Paul
Hamilton, Marta
Cameron, Terri
Barrett, Emma
Walsh, Wendy
McIntosh, Lynn
Eisenhauer, Elizabeth A
Affiliation
MBBS, MRCP, ILTM, Department of Medical Oncology, University of Newcastle, Westgate Rd, Newcastle upon Tyne, NE4 6BE, United Kingdom. graham.dark@ncl.ac.ukIssue Date
2005-03-20
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PURPOSE: Liposomal lurtotecan (OSI-211) is a liposomal formulation of the water-soluble topoisomerase I inhibitor lurtotecan (GI147211), which demonstrated superior levels of activity compared with topotecan in preclinical models. We studied two schedules of OSI-211 in a randomized design in relapsed ovarian cancer to identify the more promising of the two schedules for further study. PATIENTS AND METHODS: Eligible patients had measurable epithelial ovarian, fallopian, or primary peritoneal cancer that was recurrent after one or two prior regimens of chemotherapy. Patients were randomly assigned to receive either arm A (OSI-211 1.8 mg/m(2)/d administered by 30-minute intravenous infusion on days 1, 2, and 3 every 3 weeks) or arm B (OSI-211 2.4 mg/m(2)/d administered by 30-minute intravenous infusion on days 1 and 8 every 3 weeks). The primary outcome measure was objective response, which was confirmed by independent radiologic review, and a pick the winner statistical design was used to identify the schedule most likely to be superior. RESULTS: Eighty-one patients were randomized between October 2000 and September 2001. The hematologic toxic effects were greater on arm A than on arm B (grade 4 neutropenia, 51% v 22%, respectively), as was febrile neutropenia (26% v 2.4%, respectively). Of the 80 eligible patients, eight patients (10%) had objective responses; six responders (15.4%; 95% CI, 6% to 30%) were in arm A and two responders (4.9%; 95% CI, 1% to 17%) were in arm B. CONCLUSION: The OSI-211 daily for 3 days intravenous schedule met the statistical criteria to be declared the winner in terms of objective response. This schedule was also associated with more myelosuppression than the schedule of OSI-211 administered in arm B.Citation
Randomized trial of two intravenous schedules of the topoisomerase I inhibitor liposomal lurtotecan in women with relapsed epithelial ovarian cancer: a trial of the national cancer institute of Canada clinical trials group. 2005, 23 (9):1859-66 J. Clin. Oncol.Journal
Journal of Clinical OncologyDOI
10.1200/JCO.2005.02.028PubMed ID
15699482Type
ArticleLanguage
enISSN
0732-183Xae974a485f413a2113503eed53cd6c53
10.1200/JCO.2005.02.028
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