Department of Solid Tumor Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA,
Ann Surg Oncol. 2014 Feb;21(2):479-86. doi: 10.1245/s10434-013-3275-0. Epub 2013 Oct 24.
Systemic bevacizumab (Bev) was added to hepatic arterial infusion (HAI) floxuridine (FUDR)-based chemotherapy in three studies in an attempt to improve outcomes. A specific review of biliary toxicity was carried out.
This analysis included 203 patients from three prospective studies. The first (study A) was an adjuvant study after liver resection of colorectal metastases in which patients received HAI and systemic chemotherapy (Sys) with or without Bev. Study B comprised unresectable colorectal patients who received HAI and Sys plus Bev. Study C included patients with unresectable cholangiocarcinoma or hepatocellular carcinoma who received HAI plus systematic Bev. The outcome and toxicity of patients in studies B and C were compared with historical controls.
In all three studies, the incidence of hyperbilirubinemia and biliary stent placement within 1 year of treatment was increased with the addition of Bev. In the no-Bev versus Bev groups, the placement of biliary stents was as follows: study A, 0 of 38 versus 4 of 35 patients (p = 0.05); study B, 0 of 49 versus 3 of 24 (p = 0.06); and study C, 0 of 34 versus 3 of 22 (p = 0.15). Elevation in bilirubin was noted in the no-Bev versus Bev groups: study A, 0 of 38 versus 5 of 35 patients (p = 0.02); study B, 1 of 49 versus 7 of 24 (p = 0.005); and study C, 2 of 34 versus 5 of 22 (p = 0.10). The addition of Bev did not seem to be associated with improved progression-free or overall survival.
The addition of Bev to HAI FUDR resulted in increased biliary toxicity in three separate studies. Although the sample sizes were small, there was no evidence of improved PFS or OS with the addition of Bev. Bev should not be combined with HAI FUDR.
在三项研究中，尝试将全身性贝伐珠单抗（Bev）加入到基于肝动脉输注（HAI）氟尿嘧啶（FUDR）的化疗中，以改善疗效。本研究专门对胆道毒性进行了回顾。
本分析纳入了三项前瞻性研究中的 203 例患者。第一项（研究 A）是结直肠转移瘤肝切除术后的辅助研究，患者接受 HAI 和全身性化疗（Sys）联合或不联合 Bev。第二项（研究 B）包括不可切除的结直肠癌患者，接受 HAI 和 Sys 联合 Bev。第三项（研究 C）包括不可切除的胆管癌或肝细胞癌患者，接受 HAI 联合系统性 Bev。研究 B 和 C 的患者的治疗结局和毒性与历史对照进行了比较。
在所有三项研究中，加用 Bev 后，治疗后 1 年内高胆红素血症和胆道支架置入的发生率增加。无 Bev 组和 Bev 组的胆道支架置入情况如下：研究 A，38 例中无 1 例 vs. 35 例中有 4 例（p=0.05）；研究 B，49 例中无 1 例 vs. 24 例中有 3 例（p=0.06）；研究 C，34 例中无 1 例 vs. 22 例中有 3 例（p=0.15）。无 Bev 组和 Bev 组的胆红素升高情况如下：研究 A，38 例中无 1 例 vs. 35 例中有 5 例（p=0.02）；研究 B，49 例中无 1 例 vs. 24 例中有 7 例（p=0.005）；研究 C，34 例中无 1 例 vs. 22 例中有 5 例（p=0.10）。Bev 的加入似乎并未改善无进展生存期（PFS）或总生存期（OS）。
在三项独立研究中，将 Bev 加入到 HAI FUDR 中导致胆道毒性增加。尽管样本量较小，但 Bev 的加入并未改善 PFS 或 OS。Bev 不应与 HAI FUDR 联合使用。
