Phase III Trial Comparing Protracted Intravenous Fluorouracil Infusion Alone or With Yttrium-90 Resin Microspheres Radioembolization for Liver-Limited Metastatic Colorectal Cancer Refractory to Standard Chemotherapy
Phase III Trial Comparing Protracted Intravenous Fluorouracil Infusion Alone or With Yttrium-90 Resin Microspheres Radioembolization for Liver-Limited Metastatic Colorectal Cancer Refractory to Standard Chemotherapy
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DOI：
10.1200/jco.2010.28.5643
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发表时间：
2010-08-10
影响因子：
45.3
通讯作者：
Flamen, Patrick
中科院分区：
文献类型：
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作者：
Hendlisz, Alain;Van den Eynde, Marc;Flamen, Patrick
目的肝脏播散是晚期结直肠癌患者死亡的主要原因。肝动脉内注射β -释放同位素钇-90 （Y-90）结合到树脂微球（放射栓塞）提供治疗放射剂量的肝转移，对邻近组织的损害最小。患者和方法我们进行了一项前瞻性，多中心，随机III期试验，在不可切除，化疗难治性肝局限性转移性CRC （mCRC）患者中进行比较a组（氟尿嘧啶[FU]持续静脉输注300 mg/m(2)，每3周1至14天）和B组（放射栓塞加静脉输注氟尿嘧啶225 mg/m2，然后每3周300 mg/m2，第1至14天），直到肝脏进展。主要终点为肝脏进展时间（TTLP）。结果随机分配46例患者，其中44例符合分析条件（A组，n = 23； B组，n = 21）。中位随访时间为24.8个月。A组和B组的中位TTLP分别为2.1和5.5个月（风险比[HR] = 0.38; 95% CI, 0.20 ~ 0.72; P = 0.003）。中位肿瘤进展时间（TTP）分别为2.1和4.5个月（HR = 0.51; 95% CI, 0.28 ~ 0.94; P = 0.03）。单次FU治疗后6例出现3级或4级毒性反应，放射栓塞加FU治疗后1例出现3级或4级毒性反应（P = 0.10）。44例患者中有25例在进展后接受了进一步治疗，其中A组10例患者接受了放射栓塞治疗。A组和B组的中位总生存期分别为7.3个月和10.0个月（HR = 0.92; 95% CI, 0.47 ~ 1.78; P = 0.80）。结论y -90树脂微球联合FU放射栓塞耐受良好，与单独FU相比，TTLP和TTP明显改善。该手术是化疗难治性肝局限性mCRC的有效治疗选择。中华临床杂志，28(3):387 - 394。(C) 2010年由美国临床肿瘤学会出版
PurposeLiver dissemination is a major cause of mortality among patients with advanced colorectal cancer. Hepatic intra-arterial injection of the beta-emitting isotope yttrium-90 (Y-90) bound to resin microspheres (radioembolization) delivers therapeutic radiation doses to liver metastases with minimal damage to adjacent tissues.Patients and MethodsWe conducted a prospective, multicenter, randomized phase III trial in patients with unresectable, chemotherapy-refractory liver-limited metastatic CRC (mCRC) comparing arm A (fluorouracil [FU] protracted intravenous infusion 300 mg/m(2) days 1 through 14 every 3 weeks) and arm B (radioembolization plus intravenous FU 225 mg/m2 days 1 through 14 then 300 mg/m2 days 1 through 14 every 3 weeks) until hepatic progression. The primary end point was time to liver progression (TTLP). Cross-over to radioembolization was permitted after progression in arm A.ResultsForty-six patients were randomly assigned and 44 were eligible for analysis (arm A, n = 23; arm B, n = 21). Median follow-up was 24.8 months. Median TTLP was 2.1 and 5.5 months in arms A and B, respectively (hazard ratio [HR] = 0.38; 95% CI, 0.20 to 0.72; P = .003). Median time to tumor progression (TTP) was 2.1 and 4.5 months, respectively (HR = 0.51; 95% CI, 0.28 to 0.94; P = .03). Grade 3 or 4 toxicities were recorded in six patients after FU monotherapy and in one patient after radioembolization plus FU treatment (P = .10). Twenty-five of 44 patients received further treatment after progression, including 10 patients in arm A who received radioembolization. Median overall survival was 7.3 and 10.0 months in arms A and B, respectively (HR = 0.92; 95% CI, 0.47 to 1.78; P = .80).ConclusionRadioembolization with Y-90-resin microspheres plus FU is well tolerated and significantly improves TTLP and TTP compared with FU alone. This procedure is a valid therapeutic option for chemotherapy-refractory liver-limited mCRC. J Clin Oncol 28: 3687-3694. (C) 2010 by American Society of Clinical Oncology