Erdem Gökmen Umut, Sendur Mehmet Ali Nahit, Ozdemir Nuriye Yıldırım, Yazıcı Ozan, Zengin Nurullah
Ankara Numune Education and Research Hospital, Department of Medical Oncology , Ankara , Turkey.
Curr Med Res Opin. 2015 Apr;31(4):743-56. doi: 10.1185/03007995.2015.1018988. Epub 2015 Mar 17.
Basal cell carcinoma (BCC) is the most common cancer. Most cases of BCCs are treated with only optimal surgical resection. However, unresectable, locally advanced or metastatic tumors might have potential to progress. In this patient group, there is no standardized treatment approach. Vismodegib is a new selective inhibitor of the hedgehog (Hh) pathway. This manuscript is aimed to review the efficacy of the Hh pathway inhibitor vismodegib in BCC patients with locally advanced or metastatic disease.
Vismodegib showed positive results in clinical studies. A computerized search of the PubMed and American Society of Clinical Oncology Meeting abstracts was performed, by searching for the following keywords: 'vismodegib', 'pathway', 'inhibitor', and 'targeted therapies for BCC'. The last search was done on 1 September 2014. Most of the vismodegib data depend on phase I and II trials.
Preclinical and clinical studies have shown that Hh pathway activation occurs in BCC. In BCC patients the role of chemotherapy is not completely known. Although conventional chemotherapies like cisplatins increase the response rate in BCC, improvement in overall survival and progression free survival were not demonstrated. Results of both phase I and phase II studies have shown that vismodegib is a potential new treatment strategy for patients with locally advanced and metastatic BCC. As in previously published phase I trials, in the ERIVANCE BCC study the primary endpoint, objective response rate, significantly increased by 43% and 30% in patients with locally advanced and metastatic BCC, respectively. Because of the promising results in phase I and II trials, vismodegib was approved by the Food and Drug Administration (FDA) in the treatment of patients with BCC who are not suitable for surgery or radiotherapy or with relapsed locally advanced disease following surgery or metastatic disease.
Recent trials have shown that vismodegib has produced promising activity in patients with locally advanced and metastatic BCC. The ongoing studies with vismodegib in other solid tumors and BCC will shed light on more certain treatment pathways.
基底细胞癌（BCC）是最常见的癌症。大多数基底细胞癌病例仅通过最佳手术切除进行治疗。然而，无法切除、局部晚期或转移性肿瘤可能有进展的可能。在这组患者中，没有标准化的治疗方法。维莫德吉是一种新型的刺猬（Hh）通路选择性抑制剂。本手稿旨在综述Hh通路抑制剂维莫德吉在局部晚期或转移性基底细胞癌患者中的疗效。
维莫德吉在临床研究中显示出阳性结果。通过搜索以下关键词对PubMed和美国临床肿瘤学会会议摘要进行了计算机检索：“维莫德吉”、“通路”、“抑制剂”以及“基底细胞癌的靶向治疗”。最后一次检索于2014年9月1日进行。大多数维莫德吉数据依赖于I期和II期试验。
临床前和临床研究表明，Hh通路激活发生在基底细胞癌中。在基底细胞癌患者中，化疗的作用尚不完全清楚。尽管顺铂等传统化疗药物可提高基底细胞癌的缓解率，但未显示总生存期和无进展生存期有所改善。I期和II期研究结果均表明，维莫德吉是局部晚期和转移性基底细胞癌患者潜在的新治疗策略。正如之前发表的I期试验一样，在ERIVANCE BCC研究中，主要终点客观缓解率在局部晚期和转移性基底细胞癌患者中分别显著提高了43%和30%。由于I期和II期试验取得了令人鼓舞的结果，维莫德吉被美国食品药品监督管理局（FDA）批准用于治疗不适合手术或放疗的基底细胞癌患者，或手术后局部晚期复发或转移性疾病患者。
近期试验表明，维莫德吉在局部晚期和转移性基底细胞癌患者中产生了令人鼓舞的活性。正在进行的维莫德吉在其他实体瘤和基底细胞癌中的研究将为更明确的治疗途径提供线索。
