甲氨蝶呤、顺铂、阿霉素和异环磷酰胺治疗ⅡB期肢体骨肉瘤的临床观察

Clinical observation of methotrexate,cisplatin,adriamycin and ifosfamide for stage ⅡB extremity osteosarcoma

目的观察大剂量甲氨蝶呤(MTX)、顺铂(DDP)、阿霉素(ADM)和异环磷酰胺(IFO)4种药物两种不同组合方案治疗ⅡB期肢体骨肉瘤的疗效及毒副反应。方法回顾性分析接受4种药物化疗方案的185例ⅡB期肢体骨肉瘤患者,其中93例接受意大利IOR-OS/N-5方案(MTX8～12g/m2静滴6h,d1;用药后12h亚叶酸钙解救12次,每次15mg;DDP80～100mg/m2、ADM60mg/m2静滴,d8;IFO2.0g/m2静滴,d21～d25;美司那400mg每天IFO用后第0、4、8h静滴),92例接受优化方案(除ADM由第8天静滴改为第21天与IFO联用外,其他同IOR-OS/N-5方案)。比较两种方案的疗效及毒副反应。结果 IOR-OS/N-5方案和优化方案组的保肢率分别为52.7%(49/93)和58.7%(54/92)。两组患者的3年复发率分别为14.0%、7.6%,3年转移率分别为47.3%、30.4%,差异均有统计学意义(P<0.05);两组患者的3年生存率分别为57.0%、75.0%,差异有统计学意义(P<0.05)。两组患者的中位无病生存时间(DFS)分别为22.2个月(95%CI:16.2～28.2个月)和29.0个月(95%CI:23.8～34.3个月),差异有统计学意义(P=0.024);两组患者的中位总生存时间(OS)分别为32.2个月(95%CI:23.2～38.2个月)和36.1个月(95%CI:33.8～44.3个月),差异有统计学意义(P=0.032)。两组患者的主要毒副反应为肝功能损害、骨髓抑制、恶心呕吐等。其中3、4级肝功能损害的发生率分别为35.2%、16.6%,3、4级白细胞减少的发生率分别为22.6%、30.2%。结论将大剂量MTX、DDP、ADM和IFO这4种药物进行优化组合治疗骨肉瘤患者的耐受性好,疗效提高。

Objective To investigate the efficacy and side effects of two combinations of high-dose methotrexate（ MTX）, cisplatin（DDP）, adriamycin（ADM） and ifosfamide（IFO） in the treatment of extremity osteosarcoma patients with stage liB. Methods A retrospective analysis was conducted for 185 osteosarcoma patients treated with the four drugs mentioned above. Ninety three patients received the Italian therapeutic scheme IOR-OS/N-5 （MTX 8-12g/m2iv 6h,dl, CF 15mg at one time, 12 times; DDP 80-100mg/m2 ,ADM 60mg/m2 iv,ds;IFO 2. 0g/m2iv d21-d, mesna 400mg after IFO for 0,4,8h）and the remaining 92 patients received the therapeutic scheme optimized（MTX 8-12g/mE iv 6h, dl, CF 15mg at one time, 12times; DDP 80-100mg/m2 iv, ds ;ADM 60mg/m2 iv d21, IFO 2. 0g/ m2iv d21-d25 ,mesna 400mg after IFO for 0,4,8h）. To compare the efficacy and side effects of two therapeutic schemes. Results The limb salvage rates of IOR-OS/N-5 and optimized schemes were 52. 7% （49/93）and 58.7% （54/92）, respectively. The 3-year recurrence rates of IOR-OS/N-5 and optimized schemes were 14. 0% and 7.6% ,respectively. The 3-year metastasis rates of IOR-OS/N-5 and optimized schemes were 47. 3% and 30. 4%, respectively. The 3-year survival rates of IOR-OS/N-5 and optimized schemes were 57.0% and 75.0% with statistical significance （P 〈 0. 05 ）. The median disease-free survival times of two groups were 22. 2 months （95% CI ： 16. 2- 28.2） and 29. 0 months（95% CI ： 23.8-34. 3 ）, respectively. There was statistical significance （ P = 0. 024 ）. The median overall survival times of two groups were 32. 2 months（95% CI：23.2-38. 2） and 36. 1 months（95% CI：33. 8-44. 3） ,respectively. There was statisticalsignificance（P = 0. 032）. The main side effects were liver function damages, myelosuppression, nausea and vomiting and so on. The in- cidence rate of liver damage with grade 3-4 accounted for 35.2% and 16. 6% in IOR-OS/N-5 and optimized scheme groups, respectively. Grade 3-4 neutropenia accounted for 22. 6% and 30. 2% in two groups, respectively. Conclusion Optimization of high-dose MTX, DDP, ADM and IFO based on the Chinese patients＇ body condition increases the resistance and efficacy in the treatment of osteosarcoma.