成骨肉瘤新辅助化学药物治疗的疗效分析

目的 探讨恶性骨肿瘤新辅助化学药物治疗(化疗)的治疗经验。方法 自1996年7月至2002年12月,对113例成骨肉瘤的患者实施了术前化疗,局部广泛切除加术后化疗。其中男65例,女48例。年龄7～32岁。肿瘤部位包括：股骨近端6例,股骨干部4例,股骨远端49例,胫骨近端37例,胫骨干部2例,胫骨远端1例,肱骨近端7例,腓骨3例,锁骨1例,肩胛骨1例,骨盆骶骨各1例。外科分期(Enneking)：ⅡA7例,ⅡB106例。术前化疗2个周期,术后继续行3个周期的化疗。结果 完全有效者60例,部分有效者35例,对术前化疗无效者18例。所有术后患者的中位随访时间为3年半,最长者7年,最短者27个月。不同的手术方式术后局部复发率不同,人工关节置换组局部复发5例(8．3％),肿瘤骨灭活再植组局部复发12例(55％)。对术前化疗反应好的60例患者,随访期间有11例患者出现肺转移,占18．3％。其中有10例局部复发,均为行肿瘤骨灭活再植及灭活骨复合人工关节置换的患者。对术前化疗反应中等的35例患者中,13例出现肺转移,占37％。对术前化疗反应差的18例中,14例出现肺转移,约占78％。对本组113例成骨肉瘤的治疗结果进行了Kaplan-Meyer生存曲线分析,5年生存率为71．93％。影响患者预后最重要的因素是肿瘤对化疗的敏感性。结论 化疗原则：(1)个体化超大剂量化疗;(2)术前阿霉素(ADM)和胞嘧啶核苷二磷酸(CDP)动脉插管化疗,使用动脉泵将上述药物泵人,保持血药浓度持续高浓度,甲氨喋呤(MTX)和异环磷酰胺(IFO)静脉内给予,采取动静脉结合的双途径化疗方式;(3)对一线药物化疗效果欠佳的患者,术前加用二线药物IFO、紫衫醇;(4)化疗过程中,仔细观察,详细记录肿瘤对化疗药物的反应,了解该患者对哪种药物敏感,用于指导术后化疗方案的改进;(5)应用有效的升高白细胞药物,缩短化疗周期,提高药物的剂量强度;(6)对于出现肺转移的患者,加用三氧化二砷、紫衫醇。

Neoadjuvant chemotherapy for osteosarcoma

OBJECTIVE: To summarize the experience in neoadjuvant chemotherapy for osteosarcoma. METHODS: Between July 1996 and December 2002 113 patients, 65 males and 48 females, aged 7 approximately 31, with osteosarcoma located in pelvis (n = 2), sacrum (n = 1), proximal femur (n = 6), shaft of femur (n = 4), distal femur (n = 49), proximal tibia (n = 37), shaft of tibia (n = 2), distal tibia (n = 1), fibula (n = 3), scapula (n = 1), clavicle (n = 1), or proximal humerus, (n = 7) without metastasis, 7 of which being at the Ennecking stage of IIA and 106 of which being at the stage of IIB, underwent 2 cycles of chemotherapy with high dose methotrexate (MTX) preoperatively and then operation. If poor response was observed after the first cycle of chemotherapy MTX was abandoned and operation was performed immediately. Twenty-two patients underwent reimplantation of devitalized tumor bone and 80 patients underwent prosthetic replacement. The protocol of cisplatin, ifosfamide, and paclitaxel was adopted after operation. At least 3 cycles of chemotherapy were given postoperatively for all patients. The patients were followed up for 20 approximately 66 months. RESULTS: Sixty patients showed excellent response to the preoperative chemotherapy, 35 showed good response, and 18 showed poor response. Relapse of tumor was found in 12 out of the 22 patients (55%) receiving reimplantation of devitalized tumor bone and in 5 out of the 60 patients (8.3%) receiving prosthetic replacement. The 5-year survival rate of the whole group was 71.93%. The lung metastasis rates were 18.3%, 37%, and 78% in the preoperative excellent response group, good response group, and poor response group respectively. CONCLUSION: The neoadjuvant chemotherapy protocol with the second-line drugs such as ifosfamide and paclitaxel used to the patients responding poorly to MTX is more effective than the older protocol. Local arterial chemotherapy is feasible.