Rydzewska Larysa, Tierney Jayne, Vale Claire L, Symonds Paul R
Meta-analysis Group, MRC Clinical Trials Unit, 222 Euston Road, London, UK, NW1 2DA.
Cochrane Database Syst Rev. 2010 Jan 20(1):CD007406. doi: 10.1002/14651858.CD007406.pub2.
BACKGROUND: A prior systematic review found that giving neoadjuvant chemotherapy before surgery improved survival compared with radiotherapy. However, the role of neoadjuvant chemotherapy followed by surgery versus surgery alone is still unclear. OBJECTIVES: To assess the role of neoadjuvant chemotherapy in women with early or locally advanced cervical cancer. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), (Issue 2, 2009), MEDLINE (to March 2009), LILACS (to March 2009), Physician's Data Query (PDQ) (to March 2009). Both published and unpublished trials were sought and systematic searches of a number of trial sources were undertaken with no restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing neoadjuvant chemotherapy with surgery in women with early or locally advanced cervical cancer who had not undergone any prior treatment likely to interfere with the treatment comparison. Trials giving radical radiotherapy for inoperable tumours and/or post-operative radiotherapy were also eligible. The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), local and distant recurrence, rates of resection and surgical morbidity. DATA COLLECTION AND ANALYSIS: Data were extracted from trial reports and independently checked by two review authors. Depending on the type of outcome, trial hazard ratios (HRs) and odds ratios (ORs) were obtained or estimated from trial reports or sought from trial investigators. MAIN RESULTS: Six trials (1072 women) were identified for inclusion in the review. Although data on PFS was available for all six trials (1036 women), data on overall survival, resection rates and pathological response were only available for five trials (909 to 938 women) and data on recurrence were only available for three trials (604 women). Whilst PFS was significantly improved with neoadjuvant chemotherapy (HR = 0.76, 95% CI = 0.62 to 0.94, p = 0.01), no OS benefit was observed (HR = 0.85, 95% CI = 0.67 to 1.07, p = 0.17). Furthermore, estimates for both local (OR = 0.76, 95% CI = 0.49 to 1.17, p = 0.21) and distant (OR = 0.68, 95% CI = 0.41 to 1.13, p = 0.13) recurrence and rates of resection (OR = 1.55, 95% CI = 0.96 to 2.50, p = 0.07) only tended to be in favour of neoadjuvant chemotherapy, and heterogeneity was observed. Exploratory analyses of pathological response showed a significant decrease in adverse pathological findings with neoadjuvant chemotherapy (OR = 0.54, 95% CI = 0.39 to 0.73, p = < 0.0001 for lymph node status; OR = 0.58, 95% CI = 0.41 to 0.82, p = 0.002 for parametrial infiltration) which despite a high level of heterogeneity was still significant when the random effects model was used. There was also no difference in the effect of neoadjuvant chemotherapy according to total cisplatin dose, chemotherapy cycle length or by cervical cancer stage. AUTHORS' CONCLUSIONS: Despite outcomes tending to be in favour of neoadjuvant chemotherapy few, including overall survival, were significant. Therefore, it remains unclear whether neoadjuvant chemotherapy consistently offers a benefit over surgery alone for women with early-stage or locally advanced cervical cancer.
背景：一项先前的系统评价发现，与放疗相比，术前给予新辅助化疗可提高生存率。然而，新辅助化疗后手术与单纯手术相比的作用仍不明确。 目的：评估新辅助化疗在早期或局部晚期宫颈癌女性中的作用。 检索策略：我们检索了Cochrane对照试验中心注册库（CENTRAL，2009年第2期）、MEDLINE（截至2009年3月）、LILACS（截至2009年3月）、医师数据查询（PDQ，截至2009年3月）。同时检索了已发表和未发表的试验，并对多个试验来源进行了无限制的系统检索。 入选标准：随机对照试验（RCT），比较新辅助化疗与手术在未接受过任何可能干扰治疗比较的先前治疗的早期或局部晚期宫颈癌女性中的效果。对不可手术切除的肿瘤进行根治性放疗和/或术后放疗的试验也符合条件。主要结局是总生存期（OS）。次要结局是无进展生存期（PFS）、局部和远处复发、切除率和手术并发症发生率。 数据收集与分析：从试验报告中提取数据，并由两位综述作者独立检查。根据结局类型，从试验报告中获取或估计试验风险比（HRs）和比值比（ORs），或向试验研究者索取。 主要结果：确定了6项试验（1072名女性）纳入综述。虽然所有6项试验（1036名女性）都有PFS数据，但总生存期、切除率和病理反应的数据仅5项试验（909至938名女性）可用，复发数据仅3项试验（604名女性）可用。新辅助化疗显著改善了PFS（HR = 0.76，95%CI = 0.62至0.94，p = 0.01），但未观察到OS获益（HR = 0.85, 95%CI = 0.67至1.07，p = 0.17）。此外，局部（OR = 0.76，95%CI = 0.49至1.17，p = 0.21）和远处（OR = 0.68，95%CI = 0.41至1.13，p = 0.13）复发以及切除率（OR = 1.55，95%CI = 0.96至2.50，p = 0.07）的估计仅倾向于支持新辅助化疗，且观察到异质性。病理反应的探索性分析显示，新辅助化疗使不良病理结果显著减少（淋巴结状态：OR = 0.54，95%CI = 0.39至0.73，p = <0.0001；宫旁浸润：OR = 0.58，95%CI = 0.41至0.82，p = 0.002），尽管异质性程度较高，但使用随机效应模型时仍具有显著性。根据顺铂总剂量、化疗周期长度或宫颈癌分期，新辅助化疗的效果也没有差异。 作者结论：尽管结果倾向于支持新辅助化疗，但包括总生存期在内的很少结果具有显著性。因此，对于早期或局部晚期宫颈癌女性，新辅助化疗是否始终比单纯手术更有益尚不清楚。
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