Mocellin Simone, Pilati Pierluigi, Lise Mario, Nitti Donato
Clinica Chirurgica Generale 2, Department of Oncological and Surgical Sciences, University of Padova, via Giustiniani 2, 35128 Padova, Italy.
J Clin Oncol. 2007 Dec 10;25(35):5649-54. doi: 10.1200/JCO.2007.12.1764.
The treatment of unresectable liver-confined metastatic disease from colorectal cancer (CRC) is a challenging issue. Although locoregional treatments such as hepatic arterial infusion (HAI) claim the advantage of delivering higher doses of anticancer agents directly into the affected organ, the benefit in terms of overall survival (OS) is unclear. We quantitatively summarized the results of randomized controlled trials (RCT) comparing HAI with systemic chemotherapy (SCT).
To date, 10 RCTs have been published, for a total of 1,277 patients enrolled. For tumor response rates, relative risks (RR) and their 95% CIs were obtained from raw data; for OS, hazard ratios (HRs) and their 95% CIs were extrapolated from the Kaplan-Meier survival curves.
HAI regimens were based on floxuridine (FUDR) in nine of 10 RCTs, whereas in one RCT, fluorouracil (FU) + leucovorin was used. SCT consisted of FUDR, FU, FU + leucovorin, or a miscellany of FU and best supportive care in three, one, four, and two studies, respectively. Pooling the data, tumor response rate was 42.9% and 18.4% for HAI and SCT, respectively (RR = 2.26; 95% CI, 1.80 to 2.84; P < .0001). Mean weighted median OS times were 15.9 and 12.4 months for HAI and SCT, respectively; the meta-risk of death was not statistically different between the two study groups (HR = 0.90; 95% CI, 0.76 to 1.07; P = .24).
Currently available evidence does not support the clinical or investigational use of fluoropyrimidine-based HAI alone for the treatment of patients with unresectable CRC liver metastases, at least as a first-line therapy.
结直肠癌（CRC）不可切除的肝局限性转移疾病的治疗是一个具有挑战性的问题。尽管诸如肝动脉灌注（HAI）等局部区域治疗方法声称具有将更高剂量的抗癌药物直接输送到受影响器官的优势，但在总生存期（OS）方面的益处尚不清楚。我们对比较HAI与全身化疗（SCT）的随机对照试验（RCT）结果进行了定量总结。
迄今为止，已发表了10项RCT，共纳入1277例患者。对于肿瘤缓解率，从原始数据中获取相对风险（RR）及其95%置信区间（CI）；对于OS，从Kaplan-Meier生存曲线外推风险比（HR）及其95%CI。
在10项RCT中的9项中，HAI方案基于氟尿苷（FUDR），而在1项RCT中，使用氟尿嘧啶（FU）+亚叶酸。SCT分别在3项、1项、4项和2项研究中由FUDR、FU、FU+亚叶酸或FU与最佳支持治疗的混合方案组成。汇总数据后，HAI和SCT的肿瘤缓解率分别为42.9%和18.4%（RR=2.26；95%CI，1.80至2.84；P<.0001）。HAI和SCT的平均加权中位OS时间分别为15.9个月和12.4个月；两个研究组之间的死亡meta风险无统计学差异（HR=0.90；95%CI，0.76至1.07；P=.24）。
目前可得的证据不支持单独将基于氟嘧啶的HAI用于不可切除的CRC肝转移患者的临床或研究性治疗，至少作为一线治疗不支持。
