大剂量化疗与标准剂量化疗治疗原发性高分化骨肉瘤疗效的系统评价

目的评价大剂量化疗治疗原发性高分化骨肉瘤的疗效是否优于标准剂量化疗。方法采用Cochrane系统评价方法,检索MEDLINE、Embase、OVID、Cochrane图书馆临床对照试验数据库、中国生物医学文献光盘数据库,以及手工检索《中华肿瘤杂志》、《中国肿瘤临床》、《肿瘤》等(检索时间为自创刊至2006年2月)。由两名评价者共同评价纳入研究质量,对同质研究进行Meta分析。结果共纳入4个研究、937例原发性、非转移性、高分化肢体骨肉瘤患者。所有研究均未描述具体的随机方法、是否盲法,只有1个研究描述分配隐藏,所有研究均报告了失访及退出原因以及基线资料。大剂量化疗组在5年无瘤生存率[RR 1．10,95％CI(0．96,1．25)]、5年总生存率[RR 1．08,95％CI(0．97,1．20)]、局部复发率[RR 0．92,95％CI(0．54,1．57)]、组织学反应良好者所占的比例[RR 0．93,95％CI(0．81,1．07)]、保肢率[RR 0．97,95％CI(0．92,1．02)]方面与低剂量组相比差异无统计学意义;肿瘤对术前化疗组织学反应良好与不良的5年无瘤生存率差异有统计学意义。结论现有研究结果显示,肿瘤对术前化疗的组织学反应是骨肉瘤的一个独立的预后因素。大剂量化疗治疗原发性高分化骨肉瘤不优于低剂量化疗,但由于纳入研究存在选择性偏倚、实施偏倚、以及发表偏倚的中度可能性,很可能影响结果的可靠性,期望将来高质量的随机对照试验提供更可靠的证据。

High-dose Versus Moderate-dose Chemotherapy for Osteosarcoma:A Systematic Review

Objective To assess the efficacy of high-dose chemotherapy versus moderate-dose chemotherapy in the treatment of osteosarcoma. Methods We searched MEDLINE, EMbase, OVID database, CBMdisc, Cochrane CENTRAL Register of Controlled Trials in The Cochrane Library, and handsearched Journal of Chinese Oncology, Journal of Chinese Clinical Oncology and Tumor. The search time was updated to Feburary 2006.The quality of the included studies was evaluated by two reviewers and meta-analyses were performed on the results of homogenous studies. Results Four studies involving 937 participants with primary, high-grade and non-metastatic extremity osteosarcoma were included. All the included studies were judged to be inadequate at reporting randomization and blinding, only one reported allocation concealment. All included studies reported the number of withdrawals and the reasons for these. The meta-analyses showed that there were no significant differences in 5-year event free survival (EFS) (RR 1.10, 95% CI 0.96 to 1.25), 5-year overall survival (OS) (RR 1.08, 95% CI 0.97 tol.20), local recurrence rate (RR 0.92, 95% CI 0.54 to 1.57), proportion of good histological response (RR 0.93, 95% CI 0.81 to 1.07), proportion of limb salvage [RR 0.97, 95% CI 0.92 to 1.02) between the high-dose group and the moderate-dose group. The 5-year EFS of the good histological response group was significantly higher than in the poor histological response group [OR 2.45,95% CI 1.76 to 3.39,P<0.00001 ). Conclusions No advantage is shown for high-dose chemotherapy over moderate-dose chemotherapy in 5-year EFS, 5-year OS, local recurrence rate, proportion of good histological response and proportion of limb salvage. Histological response to preoperative chemotherapy is an independent prognosis factor for osteosarcoma. Due to the potential risk of selection bias, performance bias and publication bias, the evidence is not strong enough to judge whether high-dose chemotherapy is better than moderate-dose chemotherapy in the treatment of osteosarcoma. Our conclusion suggests that large-scale randomized trials should be performed.