Meta-Analysis Group, Medical Research Council Clinical Trials Unit, London, United Kingdom.
J Clin Oncol. 2008 Dec 10;26(35):5802-12. doi: 10.1200/JCO.2008.16.4368. Epub 2008 Nov 10.
After a 1999 National Cancer Institute (NCI) clinical alert was issued, chemoradiotherapy has become widely used in treating women with cervical cancer. Two subsequent systematic reviews found that interpretation of the benefits was complicated, and some important clinical questions were unanswered.
We initiated a meta-analysis seeking updated individual patient data from all randomized trials to assess the effect of chemoradiotherapy on all outcomes. We prespecified analyses to investigate whether the effect of chemoradiotherapy differed by trial or patient characteristics.
On the basis of 13 trials that compared chemoradiotherapy versus the same radiotherapy, there was a 6% improvement in 5-year survival with chemoradiotherapy (hazard ratio [HR] = 0.81, P < .001). A larger survival benefit was seen for the two trials in which chemotherapy was administered after chemoradiotherapy. There was a significant survival benefit for both the group of trials that used platinum-based (HR = 0.83, P = .017) and non-platinum-based (HR = 0.77, P = .009) chemoradiotherapy, but no evidence of a difference in the size of the benefit by radiotherapy or chemotherapy dose or scheduling was seen. Chemoradiotherapy also reduced local and distant recurrence and progression and improved disease-free survival. There was a suggestion of a difference in the size of the survival benefit with tumor stage, but not across other patient subgroups. Acute hematologic and GI toxicity was increased with chemoradiotherapy, but data were too sparse for an analysis of late toxicity.
These results endorse the recommendations of the NCI alert, but also demonstrate their applicability to all women and a benefit of non-platinum-based chemoradiotherapy. Furthermore, although these results suggest an additional benefit from adjuvant chemotherapy, this requires testing in randomized trials.
1999年美国国立癌症研究所（NCI）发布临床警报后，放化疗已广泛应用于宫颈癌女性患者的治疗。随后的两项系统评价发现，对其益处的解读很复杂，一些重要的临床问题仍未得到解答。
我们开展了一项荟萃分析，从所有随机试验中获取更新的个体患者数据，以评估放化疗对所有结局的影响。我们预先设定分析，以研究放化疗的效果是否因试验或患者特征而异。
基于13项比较放化疗与单纯放疗的试验，放化疗使5年生存率提高了6%（风险比[HR]=0.81，P<.001）。在放化疗后给予化疗的两项试验中，观察到更大的生存获益。使用铂类（HR=0.83，P=.017）和非铂类（HR=0.77，P=.009）放化疗的试验组均有显著的生存获益，但未发现放疗或化疗剂量及方案在获益程度上存在差异的证据。放化疗还降低了局部和远处复发及进展，并改善了无病生存期。生存获益程度在肿瘤分期方面存在差异的迹象，但在其他患者亚组中未观察到。放化疗使急性血液学和胃肠道毒性增加，但晚期毒性分析的数据过于稀少。
这些结果支持了NCI警报的建议，但也证明了其对所有女性的适用性以及非铂类放化疗的益处。此外，尽管这些结果表明辅助化疗有额外益处，但这需要在随机试验中进行验证。
