An investigator-initiated open-label clinical trial of vismodegib as a neoadjuvant to surgery for high-risk basal cell carcinoma
An investigator-initiated open-label clinical trial of vismodegib as a neoadjuvant to surgery for high-risk basal cell carcinoma
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DOI：
10.1016/j.jaad.2014.05.020
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发表时间：
2014-11-01
影响因子：
13.8
通讯作者：
Tang, Jean Yuh
中科院分区：
文献类型：
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作者：
Ally, Mina Sarah;Aasi, Sumaira;Tang, Jean Yuh
背景：Vismodegib是一种口服hedgehog通路抑制剂，被批准用于晚期基底细胞癌（BCC）。虽然大多数基底细胞癌是适合手术，切除大肿瘤的美学敏感部位可能会损害功能或cosmetis.Objective：我们试图评估减少基底细胞癌手术缺损面积后3至6个月的新辅助vismodegib.Methods：这是一个开放标签，单臂干预试验的主要结果，在目标肿瘤手术缺损面积的变化前和后vismodegib（150毫克/天）。次要结果是肿瘤面积和耐受性的变化。结果：15例入组患者中有11例，年龄在39至100岁之间，完成了试验。13个目标肿瘤切除后，平均4 - 6 - 2个月的vismodegib。总的来说，29%（14例患者中的4例）由于维莫德吉相关的副作用而无法完成超过3个月的治疗。平均基线靶肿瘤直径为3.2 cm，13个肿瘤中有10个发生在面部。总体而言，维莫德吉使手术缺损面积较基线减少了27%（95%置信区间为-45.7%至-7.9%; P = 0.006）。Vismodegib在接受不到3个月的患者中无效。在平均随访11.5（范围4-21）个月的所有肿瘤，只有1个肿瘤复发后17个月莫氏显微surgery.Limitations：随访时间短，没有安慰剂对照是limitations.Conclusion：新辅助vismodegib出现减少手术缺损面积时，为3个月或更长的非复发性基底细胞癌在功能敏感的位置。进一步的研究，更大的样本量和长期随访是必要的。
Background: Vismodegib is an oral hedgehog-pathway inhibitor approved for advanced basal cell carcinoma (BCC). Although most BCCs are amenable to surgery, excision of large tumors in aesthetically sensitive sites may compromise function or cosmesis.Objective: We sought to evaluate the reduction in BCC surgical defect area after 3 to 6 months of neoadjuvant vismodegib.Methods: This was an open-label, single-arm intervention trial with a primary outcome of change in target-tumor surgical defect area pre- and post-vismodegib (150 mg/d). Secondary outcomes were change in tumor area and tolerability.Results: Eleven of 15 enrolled patients, aged 39 to 100 years, completed the trial. Thirteen target tumors were excised after a mean of 4 6 2 months of vismodegib. In all, 29% (4 of 14 patients) could not complete more than 3 months because of vismodegib-related side effects. The mean baseline target-tumor diameter was 3.2 cm, and 10 of 13 tumors occurred on the face. Overall, vismodegib reduced the surgical defect area by 27% (95% confidence interval -45.7% to -7.9%; P = .006) from baseline. Vismodegib was not effective in patients who received less than 3 months. Over a mean follow-up of 11.5 (range 4-21) months for all tumors, only 1 tumor recurred at 17 months post-Mohs micrographic surgery.Limitations: Short follow-up time and no placebo control are limitations.Conclusion: Neoadjuvant vismodegib appears to reduce surgical defect area when taken for 3 months or longer for nonrecurrent BCCs in functionally sensitive locations. Further studies with larger sample sizes and long-term follow-up are warranted.