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.

2.50
Hdl Handle:
http://hdl.handle.net/10541/76797
Title:
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 G; Calvert, A Hilary; Grimshaw, Robert; Poole, Christopher; Swenerton, Ken; Kaye, Stan B; Coleman, Robert E; Jayson, Gordon C ( 0000-0002-8515-8944 ) ; Le, Tien; Ellard, Susan; Trudeau, Marc; Vasey, Paul; Hamilton, Marta; Cameron, Terri; Barrett, Emma; Walsh, Wendy; McIntosh, Lynn; Eisenhauer, Elizabeth A
Abstract:
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.
Affiliation:
MBBS, MRCP, ILTM, Department of Medical Oncology, University of Newcastle, Westgate Rd, Newcastle upon Tyne, NE4 6BE, United Kingdom. graham.dark@ncl.ac.uk
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 Oncology
Issue Date:
20-Mar-2005
URI:
http://hdl.handle.net/10541/76797
DOI:
10.1200/JCO.2005.02.028
PubMed ID:
15699482
Type:
Article
Language:
en
ISSN:
0732-183X
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorDark, Graham G-
dc.contributor.authorCalvert, A Hilary-
dc.contributor.authorGrimshaw, Robert-
dc.contributor.authorPoole, Christopher-
dc.contributor.authorSwenerton, Ken-
dc.contributor.authorKaye, Stan B-
dc.contributor.authorColeman, Robert E-
dc.contributor.authorJayson, Gordon C-
dc.contributor.authorLe, Tien-
dc.contributor.authorEllard, Susan-
dc.contributor.authorTrudeau, Marc-
dc.contributor.authorVasey, Paul-
dc.contributor.authorHamilton, Marta-
dc.contributor.authorCameron, Terri-
dc.contributor.authorBarrett, Emma-
dc.contributor.authorWalsh, Wendy-
dc.contributor.authorMcIntosh, Lynn-
dc.contributor.authorEisenhauer, Elizabeth A-
dc.date.accessioned2009-08-10T09:23:21Z-
dc.date.available2009-08-10T09:23:21Z-
dc.date.issued2005-03-20-
dc.identifier.citationRandomized 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.en
dc.identifier.issn0732-183X-
dc.identifier.pmid15699482-
dc.identifier.doi10.1200/JCO.2005.02.028-
dc.identifier.urihttp://hdl.handle.net/10541/76797-
dc.description.abstractPURPOSE: 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.en
dc.language.isoenen
dc.subjectCancer Recurrenceen
dc.subjectOvarian Canceren
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAntineoplastic Agents-
dc.subject.meshArea Under Curve-
dc.subject.meshCamptothecin-
dc.subject.meshCanada-
dc.subject.meshDrug Administration Schedule-
dc.subject.meshEndpoint Determination-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshInfusions, Intravenous-
dc.subject.meshMiddle Aged-
dc.subject.meshNeoplasm Recurrence, Local-
dc.subject.meshOvarian Neoplasms-
dc.titleRandomized 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.en
dc.typeArticleen
dc.contributor.departmentMBBS, MRCP, ILTM, Department of Medical Oncology, University of Newcastle, Westgate Rd, Newcastle upon Tyne, NE4 6BE, United Kingdom. graham.dark@ncl.ac.uken
dc.identifier.journalJournal of Clinical Oncologyen

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