{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Mondaca S"],"funding":["NCI NIH HHS","National Institutes of Health"],"pagination":["e39-e52"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6428631"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["18(1)"],"pubmed_abstract":["<h4>Background</h4>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.<h4>Patients and methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients."],"journal":["Clinical colorectal cancer"],"pubmed_title":["FOLFCIS Treatment and Genomic Correlates of Response in Advanced Anal Squamous Cell Cancer."],"pmcid":["PMC6428631"],"funding_grant_id":["P30 CA008748","P30 CA 008748"],"pubmed_authors":["Varghese AM","Saltz L","Hechtman JF","Yaeger R","Bates D","Mondaca S","Cercek A","Capanu M","Segal NH","Schultz N","Chatila WK","Shia J","Kundra R","Stadler ZK"],"additional_accession":[]},"is_claimable":false,"name":"FOLFCIS Treatment and Genomic Correlates of Response in Advanced Anal Squamous Cell Cancer.","description":"<h4>Background</h4>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.<h4>Patients and methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Mar","modification":"2024-11-21T09:08:43.803Z","creation":"2020-05-22T11:25:21Z"},"accession":"S-EPMC6428631","cross_references":{"pubmed":["30316684"],"doi":["10.1016/j.clcc.2018.09.005"]}}