Department of Hematology/oncology, University of New Mexico, Albuquerque, New Mexico, USA.
Department of Hematology/oncology, MD Anderson Cancer Center, Houston, Texas.
Oncologist. 2017 Oct;22(10):1158-e116. doi: 10.1634/theoncologist.2017-0168. Epub 2017 Jul 7.
There continues to be a lack of systemic options for advanced hepatocellular carcinoma (HCC); sorafenib and, very recently, regorafenib are the only approved options. There exists a potential to combine sorafenib with chemotherapeutic agents shown to be active in HCC, such as capecitabine, safely.Good tumor response was observed, with objective improvement in a few patients seldom seen by single agent sorafenib; however, because of the limited number of patients, meaningful conclusions on survival cannot be drawn.
Sorafenib is the currently approved first-line treatment for hepatocellular carcinoma (HCC). Capecitabine has antitumor activity in hepatobiliary cancers. The combination of the two, if tolerated, could possibly improve antitumor response, and survival.
Patients with advanced HCC ineligible for locoregional therapy, Eastern Cooperative Oncology Group performance status of ≤2, Child-Pugh class A or B-7 cirrhosis, hemoglobin ≥8.5 g/dL, platelets ≥50,000/μL, absolute neutrophil count (ANC) ≥1,500 cells/μL, and serum creatinine of ≤2.0 mg/dL were recruited. All subjects received a combination of sorafenib and capecitabine, on a 14-day 7-days on 7-days off schedule. The primary end point was safety and secondary end points were overall survival (OS) and disease control rate.
A total of 15 out of 47 patients met inclusion criteria. Median age was 64 years (56-79) and 77% were male. With a median follow-up of 12 months, median OS was 12.7 months (95% confidence interval [CI], 8.5-23.4). Disease control rate was 77% (complete response 8%, partial response 8%, and stable disease 61%). Common adverse events were as follows: (a) thrombocytopenia (64%); (b) anemia (14%); (c) hypophosphatemia (21%); (d) hypomagnesemia (14%); (e) hyperbilirubinemia (21%); (f) increased aspartate transaminase (AST) (14%); (g) hand-foot syndrome (21%); and (h) deep vein thrombosis (21%).
At tolerable doses, the combination of sorafenib and capecitabine seems an active and safe palliative treatment for HCC in class A and B-7 patients with cirrhosis. The small sample size does not allow comparison with single-agent sorafenib.
目前对于晚期肝细胞癌（HCC）仍缺乏系统性治疗选择；索拉非尼和最近刚获批的瑞戈非尼是仅有的两种获批药物。联合在 HCC 中显示出活性的化疗药物，如卡培他滨，有可能是安全的，且具有潜在的效果。观察到肿瘤有良好的反应，客观改善了少数单独使用索拉非尼时很少见到的患者；然而，由于患者数量有限，无法对生存情况得出有意义的结论。
索拉非尼是目前 HCC 的一线治疗药物。卡培他滨在肝胆癌中有抗肿瘤活性。如果耐受，两者联合使用可能会改善抗肿瘤反应和生存。
招募了不符合局部区域治疗条件、东部肿瘤协作组体能状态≤2、Child-Pugh 分级 A 或 B-7 肝硬化、血红蛋白≥8.5g/dL、血小板≥50000/μL、绝对中性粒细胞计数（ANC）≥1500 细胞/μL、血清肌酐≤2.0mg/dL 的晚期 HCC 患者。所有患者均接受索拉非尼联合卡培他滨治疗，方案为 14 天的 7 天用药-7 天停药。主要终点是安全性，次要终点是总生存期（OS）和疾病控制率。
47 例患者中共有 15 例符合纳入标准。中位年龄为 64 岁（56-79 岁），77%为男性。中位随访 12 个月时，中位 OS 为 12.7 个月（95%置信区间[CI]：8.5-23.4）。疾病控制率为 77%（完全缓解 8%，部分缓解 8%，稳定疾病 61%）。常见不良事件如下：（a）血小板减少症（64%）；（b）贫血（14%）；（c）低磷血症（21%）；（d）低镁血症（14%）；（e）高胆红素血症（21%）；（f）天冬氨酸转氨酶（AST）升高（14%）；（g）手足综合征（21%）；和（h）深静脉血栓形成（21%）。
在可耐受的剂量下，索拉非尼联合卡培他滨似乎是一种有效的姑息治疗方法，适用于 A 级和 B-7 级肝硬化的 HCC 患者。由于样本量小，无法与单药索拉非尼进行比较。
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