Phase II trial of pegylated-liposomal doxorubicin (Doxil™) in sarcoma
Phase II trial of pegylated-liposomal doxorubicin (Doxil™) in sarcoma
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DOI：
10.1081/cnv-120016412
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发表时间：
2003-01-01
影响因子：
2.4
通讯作者：
Skubitz, KM
中科院分区：
文献类型：
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作者：
Skubitz, KM
聚乙二醇化脂质体多柔比星（Doxil（TM））是一种独特的脂质体多柔比星形式，其中脂质体涂有甲氧基聚（乙二醇），导致网状内皮系统的吸收减少，从而导致血液中的半衰期更长，毒性特征与非聚乙二醇化脂质体不同。我们在肉瘤中进行了Doxil的11期研究。患者人群主要既往接受过治疗或被诊断为对化疗无反应。每个疗程的初始剂量为55 mg/m2，每4周一次，根据粘膜炎和手足综合征（主要限制性毒性）调整剂量。治疗通常耐受良好。在47例患者的214个可评价疗程中，毒性轻微，与既往报告相似，但剂量减少很常见。未观察到明确的心脏毒性。有：骨肉瘤6例，尤文氏瘤3例，骨外骨肉瘤1例，软骨肉瘤1例，腺泡状软组织肉瘤2例，胃肠道间质瘤15例，其他软组织肉瘤19例。47例患者中有3例获得CR或PR，尽管47例患者中有15例患者被认为从治疗中获得了临床获益。有些答复被推迟。这些数据表明，聚乙二醇化脂质体阿霉素在这个预后不良的肉瘤人群中具有活性，并且这种治疗与适度的毒性相关。
Pegylated-liposomal doxorubicin (Doxil(TM)) is a unique form of liposomal doxorubicin in which the liposomes are coated with methoxypoly (ethylene glycol), resulting in a diminished uptake by the reticuloendothelial system, leading to a longer half-life in blood and a different toxicity profile than nonpegylated liposomes. We performed a phase 11 study of Doxil in sarcoma. The patient population was primarily previously treated or had diagnoses considered unresponsive to chemotherapy. The initial dose per course was 55 mg/m(2) every four weeks with dose modification based on mucositis and hand-foot syndrome (the main limiting toxicities). Treatment was generally well tolerated. Of 214 evaluable treatment courses in 47 patients, toxicities were mild and similar to previous reports, but dose reduction was common. No definite cardiac toxicity was observed. There were: 6 osteosarcomas, 3 Ewings, I extraosseous osteosarcoma, I chondrosarcoma, 2 alveolar soft part sarcomas, 15 gastrointestinal stromal cell tumors (GIST), and 19 other soft tissue sarcomas. Three of the 47 patients received a CR or PR, although 15 of the 47 patients were felt to have derived clinical benefit from the treatment. Some responses were delayed. These data suggest that pegylated-liposomal doxorubicin has activity in this population of poor prognosis sarcoma and that this treatment is associated with modest toxicity.