FOLFCIS Treatment and Genomic Correlates of Response in Advanced Anal Squamous Cell Cancer.

Clin Colorectal Cancer 2019 03 21;18(1):e39-e52. Epub 2018 Sep 21.

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address:

Background: 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.

Patients And Methods: 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.

Results: 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.

Conclusions: FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients.

Download full-text PDF

Source
https://linkinghub.elsevier.com/retrieve/pii/S15330028183039
Publisher Site
http://dx.doi.org/10.1016/j.clcc.2018.09.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428631PMC
March 2019
4 Reads

Publication Analysis

Top Keywords

advanced anal
24
anal scc
20
patients advanced
16
anal squamous
8
first-line folfcis
8
months 95%
8
cell cancer
8
squamous cell
8
anal
8
leucovorin fluorouracil
8
genomic
7
patients
7
advanced
7
folfcis
6
scc
6
months
5
median follow-up
4
progression-free survival
4
416 months
4
months progression-free
4

Similar Publications