瑞戈非尼是一种口服多激酶抑制剂。CORRECT试验评估了瑞戈非尼在多线治疗后的转移性结直肠癌中的作用。纳入标准包括记录在案的转移性结直肠癌及在最后一种标准治疗中进展或治疗后3个月进展的转移性结直肠癌。所有病人随机以2:1入组接受最佳支持治疗联合瑞戈替尼（160mg od po，连续三周停一周）或联合安慰剂。主要终点是总生存期，次要终点包括无进展生存期，总有效率，疾病控制率，安全性及生活质量。应用单变量cox回归分析在预先设定的亚组中进行分析，以评估其疗效。结果发现：760个病人被随机分配（瑞戈替尼组505人，安慰剂组255人）。总生存期达符合预先设定的中期分析目标。瑞戈替尼组，其总生存期及无进展生存期显著高于安慰剂组（OS风险比 0.77，中位生存期6.4个月VS5个月，PFS风险比0.19，中位PFS1.9个月VS1.7个月）。在探索性亚组分析中，不同地区、不同年龄、到随机入组时的诊断时间，先前治疗方案数、K-RAS状态均观察到了OS和PFS的获益（见列表）。最常见的瑞戈替尼相关的3度以上不良反应包括：手足皮肤反应（16.6%），乏力，高血压，腹泻以及皮疹或脱屑。生活质量数据即将发布。结论：瑞戈替尼相对于安慰剂，表现出显著地提高多线治疗后转移性结直肠癌的OS和PFS，在亚组分析中也达到了获益水平。
Generic Name and Formulations:
Regorafenib 40mg; tablets.
Company:
Bayer Healthcare Pharmaceuticals Inc.
RECENT UPDATES
04/05/13
GIST indication added.
Indications for STIVARGA:
Treatment of patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy. Treatment of patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate or sunitinib malate.
Adult Dose for STIVARGA:
Swallow whole with a low-fat breakfast (contains <30% fat). 160mg once daily for the first 21 days of each 28-day cycle; until disease progression or unacceptable toxicity. Dose modifications: see full prescribing information.
Children's Dose for STIVARGA:
<18yrs: not established.
Pharmacological Class:
Kinase inhibitor.
Warnings/Precautions:
Risk of severe hepatotoxicity (may be fatal). Monitor hepatic function before starting and at least every 2 weeks during first 2 months of treatment; interrupt and reduce or discontinue if hepatotoxicity or hepatocellular necrosis occurs. Severe hepatic impairment: not recommended. Increased risk of hemorrhage; permanently discontinue if severe or life-threatening. Interrupt and reduce or permanently discontinue if dermatological toxicity occurs (eg, hand-foot skin reaction [a.k.a. palmar-plantar erythrodysesthesia], rash). Ensure BP is controlled before starting; monitor weekly for the first 6 weeks then every cycle or as clinically indicated; withhold if severe or uncontrolled. Myocardial ischemia/infarction: withhold if new or acute onset develops; resume when resolved. Discontinue if reversible posterior leukoencephalopathy syndrome or GI perforation/fistula develops. Wound healing complications: stop treatment at least 2 weeks before surgery; discontinue if wound dehiscence occurs. Fetal toxicity. Pregnancy (Category D); use effective contraception during treatment and up to 2 months after completion. Nursing mothers: not recommended.
Interactions:
Avoid concomitant strong CYP3A4 inducers (eg, rifampin, phenytoin, carbamazepine, phenobarbital, St. John’s Wort). Avoid concomitant strong CYP3A4 inhibitors (eg, clarithromycin, grapefruit juice, itraconazole, ketoconazole, posaconazole, telithromycin, voriconazole). Monitor INR levels with concomitant warfarin.
Adverse Reactions:
Asthenia/fatigue, decreased appetite and food intake, hand-foot skin reaction, diarrhea, mucositis, weight loss, infection, hypertension, dysphonia, GI and abdominal pain, rash, fever, nausea; hepatotoxicity, hemorrhage, GI perforation.
Metabolism:
Hepatic (CYP3A4, UGT1A9); 99.5% protein bound.
Elimination:
Fecal (major), renal.
Generic Availability:
NO
How Supplied:
Tabs—84 (3 x 28)