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

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。

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

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.