Seiden Michael V, Muggia Franco, Astrow Allan, Matulonis Ursula, Campos Susanna, Roche Maria, Sivret Julia, Rusk Jason, Barrett Emma
The Division of Medical Oncology, New York University, New York, NY 10016, USA.
Gynecol Oncol. 2004 Apr;93(1):229-32. doi: 10.1016/j.ygyno.2003.12.037.
To determine the safety and efficacy of a novel topoisomerase I inhibitor, liposomal lurtotecan, in patients with topotecan resistant ovarian cancer.
The trial was an open-label phase II study for patients stratified by resistance to either single agent topotecan or to a prior topotecan-containing regimen. Liposomal lurtotecan was delivered at a dose of 2.4 mg/m(2) on Days 1 and 8 of a 21-day cycle. Dose escalations and reductions were allowed based on hematologic toxicity. Patients were evaluated every two cycles for response to liposomal lurtotecan.
Twenty-two women were accrued, with 16 women resistant to single agent topotecan and 6 women resistant to topotecan given in combination with a second chemotherapy agent. Hematologic toxicity consisted of mild to moderate thrombocytopenia, anemia, and neutropenia with mild to moderate gastrointestinal toxicity and fatigue. There were no responses, although eight patients had stable disease.
Liposomal lurtotecan at this schedule demonstrates moderate hematologic toxicity and no evidence of clinical activity in a group of heavily pretreated women previously exposed to the topoisomerase I inhibitor topotecan. The study of this agent in alternative patient populations or with alternative schedules is ongoing.
确定新型拓扑异构酶I抑制剂脂质体鲁替康在对拓扑替康耐药的卵巢癌患者中的安全性和疗效。
该试验是一项开放标签的II期研究，患者按对单药拓扑替康或含拓扑替康的既往治疗方案耐药进行分层。脂质体鲁替康在21天周期的第1天和第8天以2.4mg/m²的剂量给药。根据血液学毒性允许剂量递增或递减。每两个周期评估患者对脂质体鲁替康的反应。
共纳入22名女性，其中16名对单药拓扑替康耐药，6名对拓扑替康联合第二种化疗药物耐药。血液学毒性包括轻度至中度血小板减少、贫血和中性粒细胞减少，并伴有轻度至中度胃肠道毒性和疲劳。尽管有8名患者疾病稳定，但无反应。
在此给药方案下，脂质体鲁替康显示出中度血液学毒性，在一组先前接受过拓扑异构酶I抑制剂拓扑替康大量治疗的女性中未显示出临床活性证据。正在对该药物在其他患者群体或其他给药方案中进行研究。
