Piedbois P, Buyse M, Kemeny N, Rougier P, Carlson R, Allen-Mersh T, O'Connell M, Chang A, Sondak V, Kemeny M, Levy E
J Natl Cancer Inst. 1996 Mar 6;88(5):252-8. doi: 10.1093/jnci/88.5.252.
Metastases confined to the liver cause substantial morbidity and mortality for patients with colorectal cancer. The results of several randomized clinical trials conducted to study the effectiveness of hepatic arterial infusion (HAI) of fluoropyrimidines for the treatment of such patients have suggested that this treatment, as compared with systemic administration of fluoropyrimidines, increases the likelihood of tumor response. However, the impact of HAI on survival is unclear.
A meta-analysis was carried out to provide an objective and quantitative appraisal of the benefits of HAI in terms of tumor response rate and overall patient survival.
The meta-analysis was based on individual data provided by the principal investigators of six individual trials and on summary data for one trial. Of the seven trials, five compared HAI with floxuridine (5-fluoro-2'-deoxyuridine; FUDR) and intravenous chemotherapy (IVC) with FUDR (three trials) or fluorouracil (5-FU) (two-trials), and two compared HAI with FUDR and an ad libitum control group in which some patients could be left untreated. Response data were analyzed by use of a Mantel-Haenszel test on all randomized patients. Survival data were analyzed by the use of stratified logrank test. Multivariate analyses were performed with use of the logistic regression model for tumor response and the Cox regression model for survival. All P values resulted from two-sided statistical tests. The analyses were performed by an independent secretariat and were reviewed by the collaborators.
The tumor response rate was 41% for patients allocated to HAI with FUDR or 5-FU (CR, 2%; PR, 12%). This difference was highly significant, with a response odds ratio of 0.25 (95% confidence interval = 0.16-0.40; P < 10 (-10)). Survival analyses showed a statistically significant advantage for HAI with FUDR compared with control when trials were taken into account (P = .0009) but not when the survival analysis was restricted to trials comparing HAI with FUDR and IVC with FUDR or 5-FU (P = .14).
These results confirm that HAI can achieve much higher tumor response rates than systemic chemotherapy in patients with liver metastases from colorectal cancer.
The therapeutic benefit of use of HAI with FUDR in these patients should be judged together, with an overall evaluation of this therapy in terms of convenience, toxicity, and costs. These end points should be considered in addition to tumor response and survival in further trials involving HAI.
局限于肝脏的转移灶会给结直肠癌患者带来严重的发病和死亡风险。多项旨在研究氟嘧啶肝动脉灌注（HAI）治疗此类患者有效性的随机临床试验结果表明，与氟嘧啶全身给药相比，这种治疗方式增加了肿瘤缓解的可能性。然而，HAI对生存的影响尚不清楚。
进行一项荟萃分析，以客观、定量地评估HAI在肿瘤缓解率和患者总生存方面的益处。
该荟萃分析基于六项独立试验的主要研究者提供的个体数据以及一项试验的汇总数据。在这七项试验中，五项试验比较了HAI与氟尿苷（5-氟-2'-脱氧尿苷；FUDR）以及FUDR静脉化疗（IVC）（三项试验）或氟尿嘧啶（5-FU）静脉化疗（两项试验），两项试验比较了HAI与FUDR以及一个随意对照组（其中部分患者可能未接受治疗）。对所有随机分组患者的缓解数据采用Mantel-Haenszel检验进行分析。生存数据采用分层对数秩检验进行分析。使用逻辑回归模型分析肿瘤缓解情况，使用Cox回归模型分析生存情况。所有P值均来自双侧统计检验。分析由独立秘书处进行，并由合作者进行审核。
接受HAI联合FUDR或5-FU治疗的患者肿瘤缓解率为41%（完全缓解，2%；部分缓解，12%）。这一差异具有高度显著性，缓解比值比为0.25（95%置信区间 = 0.16 - 0.40；P < 10⁻¹⁰）。生存分析表明，考虑所有试验时，与对照组相比，HAI联合FUDR具有统计学显著优势（P = .0009），但当生存分析仅限于比较HAI与FUDR以及IVC与FUDR或5-FU的试验时，差异无统计学意义（P = .14）。
这些结果证实，对于结直肠癌肝转移患者，HAI能比全身化疗实现更高的肿瘤缓解率。
在这些患者中使用HAI联合FUDR的治疗益处应与对该疗法在便利性、毒性和成本方面的全面评估一同判断。在涉及HAI的进一步试验中，除了肿瘤缓解和生存情况外，还应考虑这些终点指标。
