Originally published as JCO Early Release 10.1200/JCO.2005.02.028 on February 7 2005

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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

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

Address reprint requests to Graham G. Dark, MBBS, MRCP, ILTM, Department of Medical Oncology, University of Newcastle, Westgate Rd, Newcastle upon Tyne, NE4 6BE, United Kingdom; e-mail: graham.dark{at}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.

Supported in part by grants from the National Cancer Institute of Canada and OSI Pharmaceuticals.

Presented as a poster at the 38th Annual Meeting of the American Society of Oncology, Orlando, FL, May 18-21, 2002.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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