Vale Claire L, Tierney Jayne, Bull Sarah J, Symonds Paul R
Meta-analysis Group, MRC Clinical Trials Unit, London, UK.
Cochrane Database Syst Rev. 2012 Aug 15;2012(8):CD003915. doi: 10.1002/14651858.CD003915.pub4.
Although endometrial adenocarcinoma is a common gynaecological cancer, a comparatively small proportion of patients present with, or develop, recurrent or advanced disease. However, for those women whose disease does progress or recur the prognosis is poor and the best treatment is yet to be identified. Co-morbidity, including obesity and cardiac disease, and concerns over toxicity have prevented more extensive studies of cytotoxic chemotherapy, although there are a number of active agents.
To assess any benefits or adverse effects of cytotoxic chemotherapy in women with advanced, recurrent or metastatic endometrial adenocarcinoma.
Systematic searches of MEDLINE, EMBASE, CENTRAL and the Cochrane Gynaecological Cancer specialist trials register were conducted to identify all eligible randomised controlled trials (RCTs).Databases were searched from 1966 to January 2012. Literature searches were supplemented with searches of relevant trials registers and conference proceedings.
RCTs comparing chemotherapy versus another intervention (including different chemotherapy) in advanced disease were considered. Trials of adjuvant treatment or for sarcomatous tumours were excluded.
Data were extracted from the papers by review authors and authors of included studies contacted for further information.
Fourteen eligible trials, which recruited patients between 1974 and 2005, were identified, eight of which compared 'more' with 'less' chemotherapy. Results from these eight trials, including 1519 patients, showed that treatment consisting of 'more' chemotherapy was associated with longer overall survival (OS) (hazard ratio (HR) 0.86; 95% confidence intervals (CI) 0.77 to 0.96; P = 0.005) and with longer progression-free survival (PFS) (n = 1526; HR 0.82; 95% CI 0.74 to 0.90; P < 0.0001). However, serious acute toxicities were more common in women randomised to the more-intense chemotherapy regimens.There was no evidence to suggest that any particular doublet chemotherapy was better (or worse) than any other, or that any single-agent chemotherapy was better (or worse) than another; however, data for these two comparisons were limited. There were no comparative trials of chemotherapy with endocrine therapy or best supportive care alone.
AUTHORS' CONCLUSIONS: This review suggests that more-intense chemotherapy regimens may improve both OS and PFS for women with advanced or recurrent endometrial cancer. However, owing to inconsistencies between cytotoxic drug combinations that have been assessed in randomised trials to date, the optimum regimen has still to be defined. Future trials should aim to include measures of quality of life (QoL) and symptom control in addition to survival and progression outcomes.
虽然子宫内膜腺癌是一种常见的妇科癌症,但只有相对较小比例的患者出现复发性或晚期疾病,或疾病进展至该阶段。然而,对于那些疾病确实进展或复发的女性,预后较差,且最佳治疗方案尚未确定。合并症,包括肥胖和心脏病,以及对毒性的担忧,阻碍了对细胞毒性化疗进行更广泛的研究,尽管有多种活性药物。
评估细胞毒性化疗对晚期、复发性或转移性子宫内膜腺癌女性患者的益处或不良反应。
系统检索MEDLINE、EMBASE、CENTRAL和Cochrane妇科癌症专科试验注册库,以识别所有符合条件的随机对照试验(RCT)。检索了1966年至2012年1月的数据库。文献检索还补充了对相关试验注册库和会议论文集的检索。
考虑比较晚期疾病化疗与另一种干预措施(包括不同化疗方案)的RCT。辅助治疗试验或肉瘤肿瘤试验被排除。
综述作者从论文中提取数据,并联系纳入研究的作者以获取更多信息。
确定了14项符合条件的试验,这些试验在1974年至2005年期间招募患者,其中8项试验比较了“更多”化疗与“更少”化疗。这8项试验的结果,包括1519名患者,表明采用“更多”化疗的治疗与更长的总生存期(OS)相关(风险比(HR)0.86;可信区间(CI)95%为0.7至0.96;P = 0.005),且与更长的无进展生存期(PFS)相关(n = 1526;HR 0.82;95%CI 0.74至0.90;P < .0001)。然而,随机分配到更强化疗方案的女性中,严重急性毒性更为常见。没有证据表明任何特定的双联化疗比其他化疗更好(或更差),也没有证据表明任何单药化疗比其他化疗更好(或更差);然而,这两种比较的数据有限。没有化疗与内分泌治疗或单纯最佳支持治疗的比较试验。
本综述表明,更强的化疗方案可能改善晚期或复发性子宫内膜癌女性的总生存期和无进展生存期。然而,由于迄今为止在随机试验中评估的细胞毒性药物组合之间存在不一致性,最佳方案仍有待确定。未来的试验除了生存和疾病进展结果外,还应旨在纳入生活质量(QoL)和症状控制措施。