Sanghera P, Wong D W Y, McConkey C C, Geh J I, Hartley A
The Cancer Centre at the Queen Elizabeth Hospital, Birmingham, UK.
Clin Oncol (R Coll Radiol). 2008 Mar;20(2):176-83. doi: 10.1016/j.clon.2007.11.013. Epub 2008 Jan 14.
With the aim of improving locoregional control, the use of preoperative chemoradiotherapy (CRT) for rectal cancer has increased. A pathological complete response (pCR) is often used as a surrogate marker for the efficacy of different CRT schedules. By analysing factors affecting pCR, this analysis aims to guide the development of future trials.
Searches of Medline, EMBASE and the electronic American Society of Clinical Oncology abstract databases were carried out to identify prospective phase II and phase III trials using preoperative CRT to treat rectal cancer. Trials were eligible for inclusion if they defined: the CRT drugs, the radiation dose and the pCR rate. Phase I patients were excluded from the analysis. A multivariate analysis examined the effect of the above variables on the pCR rate and in addition the use of neoadjuvant chemotherapy, the type of publication (peer reviewed vs abstract), the year of publication and whether the cancers were stated to be inoperable, fixed or threatening the circumferential resection margin were included. The method of analysis used was weighted linear modelling of the pCR rate.
Sixty-four phase II and seven phase III trials were identified including a total of 4732 patients. Statistically significant factors associated with pCR were the use of two drugs, the method of fluoropyrimidine administration (with continuous intravenous 5-fluorouracil being the most effective) and a higher radiotherapy dose. Although the use of two drugs was associated with a higher rate of pCR, no single schedule seemed to be more effective. None of the other factors analysed significantly influenced pCR.
A higher rate of pCR is seen in studies using two drugs, infusional 5-fluorouracil and a radiotherapy dose of 45 Gy and above.
为提高局部区域控制率，直肠癌术前放化疗（CRT）的应用有所增加。病理完全缓解（pCR）常被用作不同CRT方案疗效的替代标志物。通过分析影响pCR的因素，本分析旨在指导未来试验的开展。
检索Medline、EMBASE和美国临床肿瘤学会电子摘要数据库，以确定使用术前CRT治疗直肠癌的前瞻性II期和III期试验。如果试验定义了CRT药物、放射剂量和pCR率，则符合纳入标准。I期患者被排除在分析之外。多变量分析考察了上述变量对pCR率的影响，此外还纳入了新辅助化疗的使用、出版物类型（同行评审与摘要）、出版年份以及癌症是否被声明为不可切除、固定或威胁环周切缘。所采用的分析方法是pCR率的加权线性建模。
共确定了64项II期试验和7项III期试验，包括4732例患者。与pCR相关的具有统计学意义的因素是使用两种药物、氟嘧啶给药方法（持续静脉输注5-氟尿嘧啶最有效）和更高的放疗剂量。虽然使用两种药物与更高的pCR率相关，但似乎没有单一方案更有效。分析的其他因素均未对pCR产生显著影响。
在使用两种药物、输注5-氟尿嘧啶且放疗剂量为45 Gy及以上的研究中，pCR率更高。
