Huang Kang-Bo, Liu Ran-Yi, Peng Qi-Hua, Li Zai-Shang, Jiang Li-Juan, Guo Sheng-Jie, Zhou Qiang-Hua, Liu Ting-Yu, Deng Chuang-Zhong, Yao Kai, Qin Zi-Ke, Liu Zhuo-Wei, Li Yong-Hong, Han Hui, Zhou Fang-Jian
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou , China.
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou , China.
Urol Oncol. 2019 Jan;37(1):71-77. doi: 10.1016/j.urolonc.2018.10.016. Epub 2018 Nov 14.
There are limited therapeutic options for patients with advanced penile squamous cell carcinoma (PSCC) after chemotherapy failure. Thus, we evaluated the feasibility of salvage treatment using the epidermal growth factor receptor (EGFR) mono-antibody nimotuzumab in chemotherapy-failed PSCC patients and explored potential response or resistance biomarkers.
Six chemotherapy-failed PSCC patients with locally advanced disease or distant metastasis were enrolled consecutively to nimotuzumab treatment. Clinical responses and side effects were evaluated, and genetic characteristics of cancer specimens were analyzed through the next-generation sequencing of hotspot regions in cancer-related genes.
Two of 6 patients showed partial responses, one was identified as having stable disease, while the other 3 had disease progression after nimotuzumab therapy. Side effects were all welltolerated. Genetic analysis revealed that TP53, CDKN2A, RB1, SMAD4, FLT3, and PIK3CA were the most frequently mutated genes in PSCC specimens, while altered KRAS, HRAS, EGFR, ERBB2, and FLT3 may be correlated with nimotuzumab resistance. Furthermore, 3 patients that were human papillomavirus-positive each showed clinical response or stable disease.
EGFR mono-antibody may be a potential modality for locally advanced PSCC patients after chemotherapy failure. Further large-scale clinical studies are needed to elucidate the role of human papillomavirus status and critical gene mutations in the clinical response to EGFR-targeted therapy.
对于化疗失败的晚期阴茎鳞状细胞癌（PSCC）患者，治疗选择有限。因此，我们评估了在化疗失败的PSCC患者中使用表皮生长因子受体（EGFR）单克隆抗体尼妥珠单抗进行挽救治疗的可行性，并探索潜在的反应或耐药生物标志物。
连续纳入6例化疗失败的局部晚期或远处转移的PSCC患者接受尼妥珠单抗治疗。评估临床反应和副作用，并通过对癌症相关基因热点区域的二代测序分析癌组织标本的基因特征。
6例患者中2例显示部分缓解，1例病情稳定，另外3例在尼妥珠单抗治疗后病情进展。副作用均耐受良好。基因分析显示，TP53、CDKN2A、RB1、SMAD4、FLT3和PIK3CA是PSCC标本中最常发生突变的基因，而KRAS、HRAS、EGFR、ERBB2和FLT3的改变可能与尼妥珠单抗耐药相关。此外，3例人乳头瘤病毒阳性患者均显示临床反应或病情稳定。
EGFR单克隆抗体可能是化疗失败的局部晚期PSCC患者的一种潜在治疗方式。需要进一步的大规模临床研究来阐明人乳头瘤病毒状态和关键基因突变在EGFR靶向治疗临床反应中的作用。
