Objective. To determine the safety and efficacy of a novel illudin S derivative, irofulven(MGI- 114), in patients with recurrent ovarian cancer who had received extensive prior chemotherapy. Methods. The trial was an ...Objective. To determine the safety and efficacy of a novel illudin S derivative, irofulven(MGI- 114), in patients with recurrent ovarian cancer who had received extensive prior chemotherapy. Methods. The trial was an open label phase II study. Patients initially enrolled in this study were treated every 14 days with a dose of 24 mg/m2. Unexpected retinal toxicity associated with this dose and schedule lead to modification of the dosing to 0.55 mg/kg on the same schedule with a maximum individual dose of 50 mg. Dose reductions were permitted based on both hematologic and non- hematologic toxicities. Results. Seventy- four women were accrued and stratified into two cohorts including 58 women with platinum- resistant disease and 16 with platinum- sensitive disease. Non- hematologic toxicities included nausea, vomiting, and fatigue. Thirty- one women had between one and six visual symptoms, most were Grade 1 and 2 in nature. The majority of visual toxicities resolved either during treatment or post- treatment with irofulven. There was one partial response in each cohort with 19 (33% ) and 8 (50% ) of women having stable disease in the platinum- resistant and platinum- sensitive cohorts, respectively. Conclusions. Irofulven at 24 mg/m2 on every 14- day schedule is associated with significant retinal toxicity in this patient population. Dosing at 0.55 mg/kg has persistent retinal toxicity, yet demonstrated only limited anti- tumor activity in a population of women who had received extensive prior chemotherapy.展开更多
Objective. Incorporating topotecan into standard platinum/taxane chem otherapy for advanced ovarian cancer has been complicated by myelosuppression. This study evaluated sequential doublets of topotecan and carboplati...Objective. Incorporating topotecan into standard platinum/taxane chem otherapy for advanced ovarian cancer has been complicated by myelosuppression. This study evaluated sequential doublets of topotecan and carboplatin, followed by paclita xel and carboplatin, in newly diagnosed advanced ovarian cancer patients. Method s. Forty-five patients (median age, 56 years; range, 38-77 years) with stage I II/IV disease and GOG performance status < 2 were enrolled and received four cyc les of topotecan (1.0 mg/m2/day on days 1 to 3) and carboplatin (AUC 4 on day 1) , followed by four cycles of paclitaxel (175 mg/m2 via 3-h IV infusion on day 1 ) and carboplatin (AUC 5 on day 1). All cycles were 21 days. Antitumor response was assessed after four and eight cycles; patients with clinical complete respon se (CR) underwent second-look laparotomy for determination of pathologic CR (PC R). Dose reductions were instituted for grade 4 neutropenia and thrombocytopenia , and for grade 3/4 nonhematologic toxicity. Results. Among 41 CA-125 evaluable patients, complete and partial responses were observed in 29 (70.7%) and 11 (26.8%) patients, r espectively. Of the 12 clinical CRs (43%) in 28 evaluable patients, 10 patients underwent second-look laparotomy, with 3 PCRs (30%). Median time to progressi on was 14 months and actuarial survival was 23 months. Neutropenia was the prima ry toxicity and cause of dose adjustments and delays, including two deaths. Conc lusion. The antitumor activity observed is comparable with other series, althoug h neutropenic complications were increased. Progression-free and actuarial surv ivals were slightly inferior. A Phase Ⅲtrial (GOG182) of sequential doublets in the reverse sequence is ongoing.展开更多
文摘Objective. To determine the safety and efficacy of a novel illudin S derivative, irofulven(MGI- 114), in patients with recurrent ovarian cancer who had received extensive prior chemotherapy. Methods. The trial was an open label phase II study. Patients initially enrolled in this study were treated every 14 days with a dose of 24 mg/m2. Unexpected retinal toxicity associated with this dose and schedule lead to modification of the dosing to 0.55 mg/kg on the same schedule with a maximum individual dose of 50 mg. Dose reductions were permitted based on both hematologic and non- hematologic toxicities. Results. Seventy- four women were accrued and stratified into two cohorts including 58 women with platinum- resistant disease and 16 with platinum- sensitive disease. Non- hematologic toxicities included nausea, vomiting, and fatigue. Thirty- one women had between one and six visual symptoms, most were Grade 1 and 2 in nature. The majority of visual toxicities resolved either during treatment or post- treatment with irofulven. There was one partial response in each cohort with 19 (33% ) and 8 (50% ) of women having stable disease in the platinum- resistant and platinum- sensitive cohorts, respectively. Conclusions. Irofulven at 24 mg/m2 on every 14- day schedule is associated with significant retinal toxicity in this patient population. Dosing at 0.55 mg/kg has persistent retinal toxicity, yet demonstrated only limited anti- tumor activity in a population of women who had received extensive prior chemotherapy.
文摘Objective. Incorporating topotecan into standard platinum/taxane chem otherapy for advanced ovarian cancer has been complicated by myelosuppression. This study evaluated sequential doublets of topotecan and carboplatin, followed by paclita xel and carboplatin, in newly diagnosed advanced ovarian cancer patients. Method s. Forty-five patients (median age, 56 years; range, 38-77 years) with stage I II/IV disease and GOG performance status < 2 were enrolled and received four cyc les of topotecan (1.0 mg/m2/day on days 1 to 3) and carboplatin (AUC 4 on day 1) , followed by four cycles of paclitaxel (175 mg/m2 via 3-h IV infusion on day 1 ) and carboplatin (AUC 5 on day 1). All cycles were 21 days. Antitumor response was assessed after four and eight cycles; patients with clinical complete respon se (CR) underwent second-look laparotomy for determination of pathologic CR (PC R). Dose reductions were instituted for grade 4 neutropenia and thrombocytopenia , and for grade 3/4 nonhematologic toxicity. Results. Among 41 CA-125 evaluable patients, complete and partial responses were observed in 29 (70.7%) and 11 (26.8%) patients, r espectively. Of the 12 clinical CRs (43%) in 28 evaluable patients, 10 patients underwent second-look laparotomy, with 3 PCRs (30%). Median time to progressi on was 14 months and actuarial survival was 23 months. Neutropenia was the prima ry toxicity and cause of dose adjustments and delays, including two deaths. Conc lusion. The antitumor activity observed is comparable with other series, althoug h neutropenic complications were increased. Progression-free and actuarial surv ivals were slightly inferior. A Phase Ⅲtrial (GOG182) of sequential doublets in the reverse sequence is ongoing.
