Department of Radiology, IVR Center, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8522, Japan.
Department of Internal Medicine, Dongo Hospital, Yamatotakada, Nara, Japan.
BMC Cancer. 2019 Aug 1;19(1):758. doi: 10.1186/s12885-019-5862-3.
Efficacy of treatments for colorectal liver metastases after failure of first-line chemotherapy is limited. The aim of this study was to prospectively evaluate the feasibility, tolerability, and pharmacokinetics of selective transarterial chemoembolization (TACE) with irinotecan-loaded 40 μm microspheres combined with systemic FOLFIRI for colorectal liver metastases refractory to oxaliplatin regimen.
The dose escalation study was conducted in three patient groups with different amounts of irinotecan loaded (50, 75 and 100 mg per mL-microspheres). Selective catheterization was performed to embolize subsegments or segments of located tumors using TACE navigation system. FOLFIRI was administrated 7 days after TACE. Plasma concentration was measured before and time points after administration.
Nine patients successfully underwent a total of 22 TACE procedures. Dose-limiting toxicity did not appear at any level. The overall response rate was 55.6%. The median progression free and overall survival were 8.1 and 18.2 months, respectively. The AUC and C of plasma SN-38 per 1 mg injected irinotecan dose were significantly higher in irinotecan-loaded microspheres compared with FOLFIRI (P = 0.009 and P < 0.001, respectively).
Selective TACE using 40 μm irinotecan-loaded microspheres combined with systemic FOLFIRI was feasible and safe even when a high dose of irinotecan was loaded. Irinotecan-loaded microspheres resulted in a higher plasma concentration and AUC of SN-38 than treatment with FOLFIRI. Further large scale trials to evaluate the efficacy are mandatory.
University Hospital Medical Information Network (UMIN) Clinical Trials Registry, Registration number; UMIN000015367 ; Registered date; 08,10,2014.
一线化疗失败后治疗结直肠癌肝转移的疗效有限。本研究旨在前瞻性评估伊立替康载药 40μm 微球选择性经动脉化疗栓塞（TACE）联合全身 FOLFIRI 治疗奥沙利铂耐药结直肠癌肝转移的可行性、耐受性和药代动力学。
该剂量递增研究在三组患者中进行，载药量分别为 50、75 和 100mg/mL-微球。使用 TACE 导航系统对位于肿瘤的亚段或段进行选择性导管插入以进行栓塞。TACE 后 7 天给予 FOLFIRI。在给药前和给药后时间点测量血浆浓度。
9 例患者成功接受了总共 22 次 TACE 治疗。任何剂量水平均未出现剂量限制毒性。总缓解率为 55.6%。中位无进展生存期和总生存期分别为 8.1 和 18.2 个月。与 FOLFIRI 相比，伊立替康载药微球的血浆 SN-38 每 1mg 注射伊立替康剂量的 AUC 和 C 显著更高（P=0.009 和 P<0.001）。
即使载药量高，使用 40μm 伊立替康载药微球进行选择性 TACE 联合全身 FOLFIRI 是可行且安全的。伊立替康载药微球可使 SN-38 的血浆浓度和 AUC 高于 FOLFIRI 治疗。需要进一步进行大规模试验来评估疗效。
大学医院医学信息网（UMIN）临床试验注册，注册号 UMIN000015367；注册日期 2014 年 10 月 8 日。
