拓扑异构酶I抑制剂依沙替康甲磺酸盐(DX-8951f)两种不同剂量给药方案的IIA期研究:在顺铂/紫杉醇耐药性卵巢癌患者中的应用

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There is an urgent need for new agents with activity inplatinum -and taxane -resistant epi thelial ovarian can-cer.Exatecan mesylate is a novel top oisomerase I inhibitor with potent activity against ovaria n cancer in vitro.A multicentre phase IIA study was cond ucted in patients with platinum -and taxaneresistant epit helial ovarian cancer.Fifty -seven patients with bidimensionally measurable o-varian cancer,previously exposed t o platinum and taxanes,whose disease had relapsed within 6months of platinum -containing chemotherapy were randomised to one of two intravenous schedules of exatecan m esylate;0.3mg /m 2 daily for 5days every 3weeks(Arm A )or 2.1mg /m 2 weekly for 3weeks out of 4(Arm B ).There were no re-sponses in the weekly arm and a radiological response rate of 5.3%(95%CI 0.3-21.8%)in the daily arm.Principal toxicities were myelosup pression and emesis.Grade 3/4neutropenia occurred in 29%of patients inArm A and 6%patients in Arm B.Seventyone percent of pa-tients in Arm A required red cell tran sfusions while on treatment.Exatecan is well tolerated in this poor prognosis group of patients but only has modest single agent activity when administered in a daily regimen. There is an urgent need for new agents with activity in platinum-and taxane-resistant epi thel ovarian can-cer. Exatecan mesylate is a novel top oisomerase I inhibitor with potent activity against ovaria n cancer in vitro. A multicentre phase IIA study was cond ucted in patients with platinum-and taxaneresistant epitheial ovarian cancer. Fifty-seven patients with bidimensionally measurable o-varian cancer, previously exposed to platinum and taxanes, whose disease had relapsed within 6 months of platinum-cancer chemotherapy were randomized to one of two intravenous schedules of exatecan m esylate; 0.3 mg / m 2 daily for 5 days of 3 weeks (Arm A) or 2.1 mg / m 2 weekly for 3 weeks of 4 of (Arm B) .There were no re-sponses in the weekly arm and a radiological response rate of 5.3% (95% CI 0.3-21.8%) in the daily arm. Percipal toxicities were myelosup pression and emesis. Grade 3/4 netropenia occurred in 29% of patients in Arm A and 6% patients in Arm B. Seventyone percent of pa -tients in Arm A required red cell tran sfusions while on treatment. Exatecan is well tolerated in this poor prognosis group of patients but only has modest single agent activity when administered in a daily regimen.
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