洛铂联合阿霉素、异环磷酰胺化疗方案新辅助治疗骨肉瘤的剂量探索  

Dose escalation trial of lobaplatin combined with adriamycin and ifosfamide for neoadjuvant chemotherapy in osteosarcoma

作　　者：陈国景[1] 王臻[1] 叶新红 吴智钢[1] 朱皓东[1] 石磊[1] 付军[1] 

机构地区：[1]第四军医大学西京医院骨肿瘤科,西安710032 [2]海南长安国际制药有限公司,570314

出　　处：《临床肿瘤学杂志》2014年第4期354-357,共4页Chinese Clinical Oncology

摘　　要：目的探讨洛铂(LBP)联合阿霉素(ADM)、异环磷酰胺(IFO)化疗方案新辅助治疗骨肉瘤的最大耐受量(MTD),并观察其毒副反应。方法 LBP设定3个剂量水平,分别为45mg/m2、50mg/m2、55mg/m2,ADM和IFO剂量固定(ADM 60mg/m2、IFO 12g/m2),观察到出现剂量限制性毒性(DLT)即终止试验,或至55mg/m2未出现DLT,试验亦终止。结果共有6例患者完成了爬坡试验,当试验进行到第1个剂量组时,出现2例DLT,试验终止。从而确定联合化疗方案的MTD为LBP 45mg/m2、ADM 60mg/m2和IFO 12g/m2。主要不良反应为骨髓抑制,血小板减少的发生率为66.6%(4/6),3级发生率为33.3%(2/6);白细胞减少的发生率为83.3%(5/6),未发生4级白细胞减少;中性粒细胞减少的发生率为83.3%(5/6),4级发生率为33.3%(2/6)。所有患者经对症治疗后均好转,未影响继续治疗。结论 LBP联合ADM、IFO化疗方案新辅助治疗骨肉瘤的MTD为LBP 45mg/m2、ADM 60mg/m2和IFO12g/m2,毒副反应可耐受,建议以此为依据开展进一步临床研究。Objective To investigate the maximum-tolerated dose（MTD） and observe the side effects of lobaplatin（LBP） combined with adriamycin（ ADM） and ifosfamide （ IFO） for neoadjuvant chemotherapy in osteosarcoma. Methods The doses of ADM and IFO were fixed（ ADM 60mg/m2 ,IFO 12g/m2 ） ,and three dose levels of LBP were setted, namely 45mg/m2 , 50mg/m2 , 55mg/m2 . The dose of LBP would increase gradually until dose-limiting toxicity（DLT） or 55mg/m2. Results Six cases were enrolled, and 2 DLT cases were observed when the test to the first dose group. So the MTD was LBP 45mg/m2 , ADM 60mg/m2 , IFO 12g/m2 . The main toxicities were reversible bone marrow suppression. The incidence rate of thrombocytopenia was 66？6% （ 4/6） and grade 3 was 33？3% （2/6）. The incidence rate of leukocytopenia was 83？3% （5/6） and no grade 3-4 toxicity was observed 0 （0/6）. The inci-dence of neutropenia was 83？3% （ 5/6） and grade 4 was 33？3% （ 2/6） . All patients were recovered by symptomatic treatment. Con-clusion The MTD of LBP combined with ADM and IFO as neoadjuvant chemotherapy in treating osteosarcoma is LBP 45mg/m2 , ADM 60mg/m2 , IFO 12g/m2 . The therapy is well tolerated and recommended as a basis for further clinical studies.

关 键 词：洛铂 骨肉瘤 新辅助化疗 剂量递增 耐受性 

分 类 号：R738.1[医药卫生—肿瘤]