Objective

Although sorafenib, a molecular targeted agent, has survival benefits for advanced hepatocellular carcinoma (HCC) patients, its disease control rate remains limited. To explore the potential for augmenting its antitumor effect, we assessed the preclinical and clinical efficacy and tolerability of S-1 metronomic chemotherapy (MC) plus sorafenib.

Methods

Antitumor effects and toxicity of this combination were tested with HAK-1B xenograft and spontaneous HCC mouse models, and a prospective pilot study was performed to compare therapeutic effects and safety between sorafenib plus MC S-1 for 12 advanced HCC cases and the historical control of 363 sorafenib-treated advanced HCC patients at our hospital from July 2011 to June 2015.

Results

In mice, the combination chemotherapy enhanced anti-angiogenic effects, resulting in a stronger tumor hypoxic environment and increased tumor cell apoptosis. Clinically, the objective response rate of the combination chemotherapy was higher than that of sorafenib mono therapy (16.7%; 2/12 vs 5.2%; 19/363, p < 0.05); however, there were no significant differences in overall survival and time to progression. Adverse events including alopecia, thrombocytopenia, and pancreatic enzymes elevation in the combination chemotherapy were higher than those of sorafenib. No patient treated with the combination chemotherapy discontinued treatment due to severe adverse events.

Conclusions

Sorafenib plus MC S-1 seems to be effective and tolerable for patients with advanced HCC and could be considered a treatment option for these patients.

中文翻译：

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在临床前和临床评估中索拉非尼加节拍式化疗 S-1 治疗晚期肝细胞癌的疗效和耐受性

客观的

尽管索拉非尼作为一种分子靶向药物，对晚期肝细胞癌 (HCC) 患者具有生存优势，但其疾病控制率仍然有限。为了探索增强其抗肿瘤作用的潜力，我们评估了 S-1 节拍式化疗 (MC) 加索拉非尼的临床前和临床疗效和耐受性。

方法

使用 HAK-1B 异种移植和自发性 HCC 小鼠模型测试了这种组合的抗肿瘤作用和毒性，并进行了一项前瞻性试验研究，以比较索拉非尼加 MC S-1 对 12 例晚期 HCC 病例的治疗效果和安全性以及历史对照2011年7月至2015年6月我院接受索拉非尼治疗的晚期HCC患者363例。

结果

在小鼠中，联合化疗增强了抗血管生成作用，导致更强的肿瘤缺氧环境和增加肿瘤细胞凋亡。临床上，联合化疗的客观缓解率高于索拉非尼单药治疗（16.7%；2/12 vs 5.2%；19/363，p  < 0.05）；然而，总生存期和进展时间没有显着差异。联合化疗中的脱发、血小板减少和胰酶升高等不良事件高于索拉非尼。接受联合化疗的患者没有因严重不良事件而停止治疗。

结论

索拉非尼加 MC S-1 似乎对晚期 HCC 患者有效且可耐受，可考虑作为这些患者的治疗选择。