[OSI-211 dose finding trial in ovarian cancer]
>>JCO Early Release, published online ahead of print Feb 7 2005
Journal of Clinical Oncology, 10.1200/JCO.2005.02.028
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
Graham G. Dark *, A. Hilary Calvert , Robert Grimshaw , Christopher Poole , Ken Swenerton , Stan Kaye , Robert Coleman , Gordon Jayson , Tien Le , Susan Ellard , Marc Trudeau , Paul Vasey , Marta Hamilton , Terri Cameron , Emma Barrett , Wendy Walsh , Lynn McIntosh , and Elizabeth A. Eisenhauer
From the University of Newcastle, Newcastle upon Tyne; City Hospital, National Health Services Trust, Birmingham; The Royal Marsden Hospital, Sutton Surrey; Weston Park Hospital, Cancer Research Centre, Sheffield; Christie Hospital National Health Services Trust, Manchester, United Kingdom; Queen Elizabeth II Health Sciences Centre, Victoria Site, Halifax, Nova Scotia; BC Cancer Agency, Vancouver; BC Cancer Agency, Kelowna, British Columbia; Saskatoon Cancer Centre, Saskatoon, Saskatoon; McGill University Department of Oncology, Montreal Quebec; National Cancer Institute of Canada Clinical Trials Group, Queen's University, Kingston, Ontario, Canada; Beatson Oncology Centre, Glasgow, Scotland; and OSI Pharmaceuticals, Boulder, CO.
* To whom correspondence should be addressed. E-mail: graham.dark@ncl.ac.uk
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/m2/d administered by 30-minute intravenous infusion on days 1, 2, and 3 every 3 weeks) or arm B (OSI-211 2.4 mg/m2/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.<<
Cheers, Tuck |
