Hepatic arterial infusion versus systemic therapy for hepatic metastases from colorectal cancer: A randomized trial of efficacy, quality of life, and molecular markers (CALGB 9481)
Hepatic arterial infusion versus systemic therapy for hepatic metastases from colorectal cancer: A randomized trial of efficacy, quality of life, and molecular markers (CALGB 9481)
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DOI：
10.1200/jco.2005.03.8166
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发表时间：
2006-03-20
影响因子：
45.3
通讯作者：
Mayer, RJ
中科院分区：
文献类型：
--
作者：
Kemeny, NE;Niedzwiecki, D;Mayer, RJ
目的 肝转移瘤的大部分血液供应来自肝动脉；因此，对于结直肠癌肝转移患者，肝动脉灌注（HAI）化疗可能会改善预后。方法在一项多机构试验中，135 名患者被随机分配接受 HAI 治疗与全身推注氟尿嘧啶和亚叶酸治疗。主要终点是生存；次要终点是缓解、复发、毒性、生活质量、费用和分子标志物的影响。 结果 与全身治疗相比，HAI 的总生存期显着更长（中位为 24.4 个月 vs 20 个月；P = .0034），缓解率（47% 和 24%；P = .012）和肝进展时间（THP；9.8 个月 vs 7.3 个月；P = .034）也更长。 HAI 组的肝外进展时间（7.7 个月 vs 14.8 个月；P = .029）显着缩短。生活质量测量显示，在 3 个月和 6 个月的随访评估中，HAI 组的身体机能有所改善。 HAI 和全身治疗组的毒性分别包括≥3 级中性粒细胞减少症（2% 和 45%；P < .01）、口腔炎（0% 和 24%；P < .01）和胆红素升高（18.6% 和 0；P < .01）。接受 HAI 的男性与女性相比，经历胆道毒性的比例更高（分别为 37% 和 15%；P = .05）。对于肿瘤中胸苷酸合酶水平低于或>= 4 的 HAI 患者，中位生存期分别为 24 和 14 个月 (P = .17)。 结论 与全身治疗相比，HAI 治疗可提高总体生存率、缓解率、THP，并且与更好的身体功能相关。还需要开展更多研究来探讨新化疗药物与单独 HAI 或 HAI 与新药物联合治疗的总体效益和成本。
Purpose Hepatic metastases derive most of their blood supply from the hepatic artery; therefore, for patients with hepatic metastases from colorectal cancer, hepatic arterial infusion (HAI) of chemotherapy may improve outcome.Methods In a multi-institutional trial, 135 patients were randomly assigned to receive HAI versus systemic bolus fluorouracil and leucovorin. The primary end point was survival; secondary end points were response, recurrence, toxicity, quality of life, cost, and the influence of molecular markers.Results Overall survival was significantly longer for HAI versus systemic treatment (median, 24.4 v 20 months; P = .0034), as were response rates (47% and 24%; P = .012) and time to hepatic progression (THP; 9.8 v 7.3 months; P = .034). Time to extrahepatic progression (7.7 v 14.8 months; P = .029) was significantly shorter in the HAI group. Quality-of-life measurements showed improved physical functioning in the HAI group at the 3- and 6-month follow-up assessments. Toxicity included grade >= 3 neutropenia (2% and 45%; P < .01), stomatitis (0% and 24%; P < .01), and bilirubin elevation (18.6% and 0; P < .01) in the HAI and systemic treatment groups, respectively. A greater proportion of men versus women receiving HAI experienced biliary toxicity (37% and 15%, respectively; P = .05). For HAI patients with thymidylate synthase levels in tumor less than or >= 4, the median survival was 24 and 14 months, respectively (P = .17).Conclusion HAI therapy increased overall survival, response rate, THP, and was associated with better physical functioning compared with systemic therapy. Additional studies need to address the overall benefit and cost of new chemotherapy agents versus HAI alone or the combination of HAI with new agents.