Medicine Department, Institut Jules Bordet, Brussels, Belgium.
J Clin Oncol. 2010 Aug 10;28(23):3687-94. doi: 10.1200/JCO.2010.28.5643. Epub 2010 Jun 21.
Liver dissemination is a major cause of mortality among patients with advanced colorectal cancer. Hepatic intra-arterial injection of the beta-emitting isotope yttrium-90 ((90)Y) bound to resin microspheres (radioembolization) delivers therapeutic radiation doses to liver metastases with minimal damage to adjacent tissues.
We 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/m(2) days 1 through 14 then 300 mg/m(2) 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.
Forty-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).
Radioembolization with (90)Y-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.
肝转移是晚期结直肠癌患者死亡的主要原因。β发射同位素钇-90（90Y）与树脂微球结合的肝动脉内注射（放射性栓塞）将治疗辐射剂量递送到肝转移灶，同时对邻近组织的损伤最小。
我们进行了一项前瞻性、多中心、随机 III 期试验，纳入了无法切除、化疗耐药的肝局限性转移性结直肠癌（mCRC）患者，比较了 A 臂（氟尿嘧啶[FU]持续静脉输注 300 mg/m2，第 1 天至第 14 天，每 3 周 1 次）和 B 臂（放射性栓塞联合静脉 FU 225 mg/m2，第 1 天至第 14 天，然后每 3 周 1 次，第 1 天至第 14 天 300 mg/m2），直至肝进展。主要终点是肝进展时间（TTLP）。A 臂进展后允许交叉至放射性栓塞。
46 例患者随机分配，44 例符合分析条件（A 臂，n=23；B 臂，n=21）。中位随访时间为 24.8 个月。A 臂和 B 臂的中位 TTLP 分别为 2.1 和 5.5 个月（风险比[HR]=0.38；95%CI，0.20 至 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 至 0.94；P=0.03）。FU 单药治疗后有 6 例患者发生 3 级或 4 级毒性，FU 联合放射性栓塞治疗后有 1 例患者发生 3 级或 4 级毒性（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 10 例 A 臂患者接受了放射性栓塞。A 臂和 B 臂的中位总生存期分别为 7.3 和 10.0 个月（HR=0.92；95%CI，0.47 至 1.78；P=0.80）。
与 FU 单药治疗相比，（90）Y 树脂微球联合 FU 的放射性栓塞具有良好的耐受性，可显著提高 TTLP 和 TTP。对于化疗耐药的肝局限性 mCRC，该方法是一种有效的治疗选择。
