Tanaka Akira, Sadahiro Sotaro, Suzuki Toshiyuki, Okada Kazutake, Saito Gota
Dept. of Gastroenterological Surgery, Tokai University School of Medicine.
Gan To Kagaku Ryoho. 2014 Oct;41(10):1231-6.
Regorafenib is an orally administered multikinase inhibitor that was approved for the treatment of unresectable metastatic colorectal cancer in Japan last year, following an international phase 3 trial(CORRECT)that provided evidence of a survival benefit. However, some concerns remain about high odd ratios of specific adverse events.
We examined the clinical records of 16 patients(age: 57-78 years)treated with regorafenib for metastatic colorectal cancer that had progressed after all standard therapies were administered. Patients received either 160 mg(standard dose)or 80 mg(reduced at the physician's discretion)of regorafenib orally once a day, for the first 3 weeks of each 4-week cycle. Predefined dose reduction(by 40 mg, once)and dose interruption were permitted to manage treatment-related toxic effects.
The median duration of treatment was 6.5 weeks(interquartile ratio[IQR]: 3.8-21.8). Dose modifications were required in 87.5% of patients, resulting in a relative dose intensity of 48.8%. Adverse events of grade 3 or higher related to regorafenib were hand-foot skin reactions(44%), fatigue(13%), thrombocytopenia(13%), anorexia(6%), and hypertension( 6%), in addition to severe drug-induced liver injury in 1 patient. Disease control was achieved in 75.0%(95% confidence interval[CI]: 50.0-93.8)of patients, although no patient had a partial response. Progression-free survival(PFS) and overall survival(OS)were 9.0 weeks(8.5-9.5 weeks)and 26.6 weeks(5.0-48.1 weeks), respectively.
The efficacy of regorafenib was confirmed in late-stage cases that were refractory to standard chemotherapies. Most adverse events were manageable, although treatment was discontinued permanently in some cases because of hand-foot skin reactions, fatigue, and liver injury. The duration of treatment was short, but disease control, OS, and PFS were similar to those found in the CORRECT trial.
瑞戈非尼是一种口服多激酶抑制剂，去年在日本获批用于治疗不可切除的转移性结直肠癌，此前一项国际3期试验（CORRECT）提供了生存获益的证据。然而，对于特定不良事件的高比值比仍存在一些担忧。
我们研究了16例（年龄57 - 78岁）接受瑞戈非尼治疗转移性结直肠癌患者的临床记录，这些患者在接受所有标准治疗后病情进展。患者在每4周周期的前3周，每天口服160mg（标准剂量）或80mg（由医生酌情减量）瑞戈非尼。允许进行预定义的剂量减少（减少40mg，一次）和剂量中断以处理与治疗相关的毒性作用。
中位治疗持续时间为6.5周（四分位间距[IQR]：3.8 - 21.8）。87.5%的患者需要调整剂量，导致相对剂量强度为48.8%。与瑞戈非尼相关的3级或更高等级的不良事件包括手足皮肤反应（44%）、疲劳（13%）、血小板减少（13%）、厌食（6%）和高血压（6%），此外有1例患者出现严重药物性肝损伤。75.0%（95%置信区间[CI]：50.0 - 93.8）的患者实现了疾病控制，尽管没有患者出现部分缓解。无进展生存期（PFS）和总生存期（OS）分别为9.0周（8.5 - 9.5周）和26.6周（5.0 - 48.1周）。
瑞戈非尼在对标准化疗难治的晚期病例中疗效得到证实。大多数不良事件是可控的，尽管在某些情况下由于手足皮肤反应、疲劳和肝损伤而永久停药。治疗持续时间较短，但疾病控制、总生存期和无进展生存期与CORRECT试验中的结果相似。
