Rosati Gerardo, Del Gaudio Nunzio, Scarano Enrico, Cifarelli Rosa Anna, Altucci Lucia, Bilancia Domenico
Medical Oncology Unit, S Carlo Hospital, Potenza Department of Biochemistry, Biophysics and General Pathology, University of Campania "Luigi Vanvitelli", Napoli Radiology Department, S Carlo Hospital, Potenza Metapontum Agrobios, Metaponto di Bernalda, Matera, Italy.
Medicine (Baltimore). 2018 Jun;97(25):e11178. doi: 10.1097/MD.0000000000011178.
Regorafenib is an oral multikinase inhibitor and is approved as salvage therapy in the standard treatment of advanced colorectal cancer (CRC). Due to its limited efficacy, toxicity profile, and cost, it is necessary to identify those patients who may have the most benefit from regorafenib. In a previous case report, kinase insert domain receptor (KDR) mutation has been associated with exceptional clinical response (CR) in an elderly patient treated with a low dose of regorafenib; thus, it was hypothesized that it could represent a new predictive marker of drug response.
A heavily pretreated 67-year-old man with a wide peripancreatic recurrence of colon carcinoma and liver metastases was subjected to treatment with regorafenib.
After 3 months of therapy, a computed tomography scan showed an impressive reduction of disease.
Regorafenib was given at full doses (160 mg/die for 21 days, every 4 weeks).
A lasting response without relevant toxicity. No KDR mutation relief was detected. After 13 months from the start of treatment, the patient died after the diagnosis of encephalic metastases.
Regorafenib can lead to an unexpected and durable CR with consistent progression-free survival and overall survival benefit even in patients affected by polychemotherapy refractory metastatic CRC. Further studies are needed to establish the benefit of KDR mutation as predictive marker for regorafenib sensitivity for patients with CRC. We include a detailed revision of prognostic and predictive factors of clinical outcome identified in literature to optimize the use of regorafenib in this setting.
瑞戈非尼是一种口服多激酶抑制剂，被批准作为晚期结直肠癌（CRC）标准治疗中的挽救疗法。由于其疗效有限、毒性特征和成本等因素，有必要确定那些可能从瑞戈非尼中获益最大的患者。在之前的一份病例报告中，激酶插入结构域受体（KDR）突变与一名接受低剂量瑞戈非尼治疗的老年患者的卓越临床缓解（CR）相关；因此，推测它可能代表一种新的药物反应预测标志物。
一名67岁的男性，结肠癌伴广泛胰周复发和肝转移，接受过多种治疗，现接受瑞戈非尼治疗。
治疗3个月后，计算机断层扫描显示疾病明显减轻。
给予瑞戈非尼全剂量（160mg/天，共21天，每4周一次）。
获得持久缓解且无相关毒性。未检测到KDR突变缓解。治疗开始13个月后，患者在诊断为脑转移后死亡。
瑞戈非尼可导致意外且持久的CR，即使在对多种化疗难治的转移性CRC患者中也能带来一致的无进展生存期和总生存期获益。需要进一步研究来确定KDR突变作为CRC患者瑞戈非尼敏感性预测标志物的益处。我们对文献中确定的临床结局的预后和预测因素进行了详细综述，以优化瑞戈非尼在这种情况下的使用。
