Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.
Clin Colorectal Cancer. 2019 Mar;18(1):e39-e52. doi: 10.1016/j.clcc.2018.09.005. Epub 2018 Sep 21.
Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC.
We reviewed all patients with advanced anal SCC receiving first-line FOLFCIS chemotherapy - essentially a FOLFOX (leucovorin, fluorouracil, and oxaliplatin) schedule with cisplatin substituted for oxaliplatin - in our institution between 2007 and 2017, and performed deep sequencing to identify genomic markers of response and key genomic drivers.
Fifty-three patients with advanced anal SCC (48 metastatic; 5 unresectable, locally advanced) received first-line FOLFCIS during this period; all were platinum-naive. The response rate was 48% (95% confidence interval [CI], 32.6%-63%). With a median follow-up of 41.6 months, progression-free survival and overall survival were 7.1 months (95% CI, 4.4-8.6 months) and 22.1 months (95% CI, 16.9-28.1 months), respectively. Among all patients with advanced anal SCC that underwent sequencing during the study period, the most frequent genomic alterations consisted of chromosome 3q amplification (51%) and mutations in PIK3CA (29%) and KMT2D (22%). No genomic alteration correlated with response to platinum-containing treatment. Although there were few cases, patients with human papillomavirus-negative anal SCC did not appear to benefit from FOLFCIS, and all harbored distinct genomic profiles with TP53, TERT promoter, and CDKN2A mutations.
FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients.
晚期肛门鳞状细胞癌（SCC）的治疗通常采用顺铂和 5-氟尿嘧啶联合治疗，但患者间反应存在差异，且毒性较大。我们研究了改良方案 FOLFCIS（亚叶酸、氟尿嘧啶和顺铂）的安全性和有效性，并对肛门 SCC 进行了综合临床和基因组分析。
我们回顾了 2007 年至 2017 年期间在我院接受一线 FOLFCIS 化疗（本质上是 FOLFOX[亚叶酸、氟尿嘧啶和奥沙利铂]方案，用顺铂替代奥沙利铂）的所有晚期肛门 SCC 患者，并进行了深度测序，以确定反应的基因组标记和关键基因组驱动因素。
在此期间，53 例晚期肛门 SCC 患者（48 例转移性；5 例不可切除局部晚期）接受了一线 FOLFCIS 治疗；所有患者均为铂类初治。客观缓解率为 48%（95%置信区间[CI]，32.6%-63%）。中位随访 41.6 个月时，无进展生存期和总生存期分别为 7.1 个月（95%CI，4.4-8.6 个月）和 22.1 个月（95%CI，16.9-28.1 个月）。在研究期间接受测序的所有晚期肛门 SCC 患者中，最常见的基因组改变包括染色体 3q 扩增（51%）和 PIK3CA（29%）和 KMT2D（22%）突变。没有基因组改变与含铂治疗的反应相关。虽然病例较少，但 HPV 阴性肛门 SCC 患者似乎不能从 FOLFCIS 中获益，且所有患者均具有独特的基因组特征，包括 TP53、TERT 启动子和 CDKN2A 突变。
FOLFCIS 作为晚期肛门 SCC 患者的一线化疗方案，疗效和安全性良好，是这些患者的另一种治疗选择。
