骨肉瘤的化学辅助治疗：我们处于什么位置？

Chemotherapeutic adjuvant treatment for osteosarcoma: where do we stand?

机构信息

Department of Paediatric Oncology, Leiden University Medical Center, The Netherlands.

出版信息

Eur J Cancer. 2011 Nov;47(16):2431-45. doi: 10.1016/j.ejca.2011.05.030. Epub 2011 Jun 22.

DOI:10.1016/j.ejca.2011.05.030

PMID:21703851

Abstract

AIM

Since the introduction of chemotherapy, survival in localised high-grade osteosarcoma has improved considerably. However, there is still no worldwide consensus on a standard chemotherapy approach. In this systematic review evidence for effectiveness of each single drug and the role of response guided salvage treatment of adjuvant chemotherapy are addressed, whereas in a meta-analysis the number of drugs in current protocols is considered.

METHODS

A systematic literature search for clinical studies in localised high-grade osteosarcoma was undertaken, including both randomised and non-randomised trials. Historical clinical studies from the pre-chemotherapy era were included for comparison purposes.

RESULTS

Nine historical studies showed a long-term survival of 16% after only local treatment. Fifty single agent phase II studies showed high response rates for adriamycin (A, 43%), ifosfamide (Ifo, 33%), methotrexate (M, 32%), cisplatin (P, 26%) but only 4% for etposide (E). In 19 neo-adjuvant studies the mean 5-year event free survival (EFS) was 48% for 2-drug regimens and 58% for ⩾3 drug regimens, with a 5-year overall survival (OAS) of 62% and 70%, respectively. Meta-analysis showed that ⩾3 drug regimens including methotrexate plus adriamycin plus cisplatin (plus ifosfamide) (MAP(Ifo)) had significant better outcome (EFS: HR=0.701 (95% confidence interval [95% CI]: 0.615-0.799); OAS: HR=0.792 (95% CI: 0.677-0.926) than 2-drug regimens, but there was no significant difference between MAP and MAPIfo (or plus etoposide). Salvage of poor responders by changing drugs, or intensifying treatment postoperatively has not proven to be useful in this analysis.

CONCLUSION

Meta-analysis in patients with localised high-grade osteosarcoma shows that 3-drug regimens, for example MAP are the most efficacious drug regimens.

摘要

目的

自化疗引入以来，局部高级别骨肉瘤的生存率已大幅提高。然而，目前仍然没有全球共识的标准化疗方法。本系统评价旨在探讨每种单一药物的有效性，以及辅助化疗中基于反应的挽救性治疗的作用，而荟萃分析则考虑了目前方案中药物的数量。

方法

系统检索了局部高级别骨肉瘤的临床研究，包括随机和非随机试验。为了进行比较，还纳入了化疗前时代的历史临床研究。

结果

9 项历史研究表明，仅局部治疗后，长期生存率为 16%。50 项单药 II 期研究显示阿霉素（A）、异环磷酰胺（Ifo）、甲氨蝶呤（M）、顺铂（P）的高缓解率分别为 43%、33%、32%、26%，而依托泊苷（E）仅为 4%。在 19 项新辅助研究中，2 种药物方案的 5 年无事件生存率（EFS）平均为 48%，≥3 种药物方案的 EFS 为 58%，5 年总生存率（OAS）分别为 62%和 70%。荟萃分析显示，包括甲氨蝶呤+阿霉素+顺铂（加异环磷酰胺）（MAP（Ifo））在内的≥3 种药物方案的结局显著更好（EFS：HR=0.701（95%置信区间[95%CI]：0.615-0.799）；OAS：HR=0.792（95%CI：0.677-0.926）优于 2 种药物方案，但 MAP 与 MAP（Ifo）或加依托泊苷之间无显著差异。在本分析中，改变药物或术后强化治疗来挽救反应差的患者并不能证明是有效的。