Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Department of Internal Medicine, Institute for Cancer Research, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
Cancer Res Treat. 2019 Jul;51(3):1128-1134. doi: 10.4143/crt.2018.379. Epub 2018 Nov 21.
Simvastatin has demonstrated anti-tumor activity in preclinical studies via tumor cell senescence, apoptosis, and anti-angiogenesis. This phase II trial evaluated the efficacy and toxicity profile of conventional XELOX and bevacizumab chemotherapy plus simvastatin in metastatic colorectal cancer patients (MCRC).
Patients with MCRC received first-line XELOX in 3-week treatment cycles of intravenous oxaliplatin 130 mg/m2 plus bevacizumab 7.5 mg/kg (day 1), followed by oral capecitabine 1,000 mg/m2 twice daily (day 1-14). Simvastatin 80 mg tablets were taken orally once daily every day during the period of chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, duration of response, overall survival (OS), time to progression, and toxicity.
From January 2014 to April 2015, 60 patients were enrolled and 55 patients were evaluable for tumor response. The median follow-up duration was 30.1 months (range, 28.5 to 31.7 months). The median PFS was 10.4 months (95% confidence interval [CI], 9.6 to 11.1). The median OS of all patients was 19.0 months (95% CI, 11.9 to 26.0). The disease-control rate and overall response rate were 88.3% (95% CI, 74 to 96) and 58.3% (95% CI, 44 to 77), respectively, by intent-to-treat protocol analysis. There was one complete response and 34 partial responses. One patient experienced grade 3 creatine kinase elevation and liver enzyme elevation.
Based on the current study, the addition of 80 mg simvastatin to XELOX and bevacizumab showed comparable clinical efficacy in patients with MCRC as first-line chemotherapy and did not increase toxicity.
辛伐他汀在临床前研究中通过肿瘤细胞衰老、凋亡和抗血管生成显示出抗肿瘤活性。本 II 期试验评估了转移性结直肠癌患者（MCRC）中常规 XELOX 和贝伐单抗化疗联合辛伐他汀的疗效和毒性特征。
MCRC 患者接受一线 XELOX，静脉注射奥沙利铂 130mg/m2 加贝伐单抗 7.5mg/kg（第 1 天），随后口服卡培他滨 1000mg/m2，每日 2 次（第 1-14 天）。在化疗期间，辛伐他汀 80mg 片剂每日一次口服。主要终点是无进展生存期（PFS）。次要终点是反应率、反应持续时间、总生存期（OS）、进展时间和毒性。
从 2014 年 1 月至 2015 年 4 月，共纳入 60 例患者，55 例患者可评估肿瘤反应。中位随访时间为 30.1 个月（范围，28.5 至 31.7 个月）。中位 PFS 为 10.4 个月（95%置信区间[CI]，9.6 至 11.1）。所有患者的中位 OS 为 19.0 个月（95%CI，11.9 至 26.0）。按意向治疗方案分析，疾病控制率和总反应率分别为 88.3%（95%CI，74%至 96%）和 58.3%（95%CI，44%至 77%）。有 1 例完全缓解和 34 例部分缓解。1 例患者出现 3 级肌酸激酶升高和肝酶升高。
根据本研究，XELOX 和贝伐单抗中添加 80mg 辛伐他汀作为一线化疗在转移性结直肠癌患者中显示出相当的临床疗效，且不会增加毒性。
