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

Abstract

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.

Liposomal, Nanoparticle, and Conjugated Formulations of Anticancer Agents

“…Immunoliposomes that contain an antibody conjugated to a liposome are being developed to provide targeted delivery to cancer cells expressing specific proteins (8, 67). Future studies need to evaluate the mechanism of clearance of liposomal and nanoparticle drug formulations and the factors associated with pharmacokinetic variability (19,37,41,42,50,67). In addition, additional preclinical models are needed for toxicity, efficacy, and pharmacokinetic studies, especially because liposomes may not be allometrically scaled across species and toxicity in certain species may not predict human toxicity (50,68).…”

“…(52). Liposomal encapsulation of camptothecins is an attractive formulation due to the solubility issues associated with most camptothecin analogues and the potential for prolonged exposure after administration of a single dose (37,41,50). As compared with pegylated or coated liposomes, conventional liposomal formulations of camptothecin analogues, such as LE-SN38 and OSI-211, may result in the rapid release of the drug from the liposome in blood and thus act more as a new i.v.…”

Concept and Clinical Evaluation of Carrier-Mediated Anticancer Agents

“…Nanosomal encapsulation of camptothecins is an attractive formulation because of the solubility issues associated with most camptothecin analogues, maintenance of the drug in the active lactone form, and the potential for prolonged exposure after administration of a single dose [59,61,66]. Some of the nanosomal formulations of camptothecin analogues that are currently in development are liposome encapsulated SN-38 (LE-SN38) [61][62][63][64], lurtotecan (OSI-211) [59,60,67,68], 9-nitrocamptothecin (9NC) [69 -71], pegylated (IHL-305 and nanoliposomal CPT-11) and nonpegylated irinotecan [2,[52][53][54]72], S-CKD602 [32,33], and TLI [56].…”

“…Some of the nanosomal formulations of camptothecin analogues that are currently in development are liposome encapsulated SN-38 (LE-SN38) [61][62][63][64], lurtotecan (OSI-211) [59,60,67,68], 9-nitrocamptothecin (9NC) [69 -71], pegylated (IHL-305 and nanoliposomal CPT-11) and nonpegylated irinotecan [2,[52][53][54]72], S-CKD602 [32,33], and TLI [56]. A randomized phase II trial of OSI-211 in patients with relapsed ovarian cancer comparing OSI-211 i.v.…”

“…on days 1, 2, and 3 repeated every 3 weeks with OSI-211 i.v. on days 1 and 8 repeated every 3 weeks was performed [59]. OSI-211 daily for 3 days was declared the winner in terms of objective response.…”