Neoadjuvant FLOT: Real world toxicity from a specialist UK centre
Authors: Z. Kordatou, G. Papaxoinis, T. Waddell, V. Owen-Holt, J. Weaver, R. Hubner, W. Mansoor
Journal: Annals of Oncology (2018)

Introduction: Perioperative FLOT (5FU/leucovorin, oxaliplatin, docetaxel) improved all efficacy endpoints in resectable gastroesophageal adenocarcinoma (GOA), compared to ECF/X. This analysis aims to assess the tolerability of patients of our institution, and to compare with the reported toxicity rates of the AIO-FLOT4 trial. Methods: Clinical information was retrieved from patient notes and electronic files of patients undergoing neoadjuvant FLOT (November 2017-February 2018). All reported adverse events and hospital admissions were recorded and analysed. The analysis focused only on the neoadjuvant component of treatment. Results: Thirty-nine patients with resectable GOA commenced FLOT. Only 33 patients that completed/discontinued their neoadjuvant course by the time of the analysis were included. Demographics: males (n = 27, 82%), mean age 62 (range: 38-84). Tumour location: gastric (n = 3, 9%), GOJ (n = 16, 49%), and lower oesophagus (n = 14, 42%). Sixteen patients had node-positive disease (48.5%). Performance status (PS) prior to treatment: 0 (n = 26, 78.8%) and 1 (n = 7, 21.2%). Twenty-two patients (67%) completed 4 cycles. Three patients (9%) discontinued treatment after 3 cycles, 4 (12%) after 2 cycles, and 4 (12%) after 1 cycle. Twenty-three patients (70%) had at least 1 hospital admission during treatment, with mean duration 5.8 days (range 1-22). Commonest reasons for admission were non-neutropenic fever/infection (n = 9, 27%) and diarrhoea (n = 6, 19%). Thirteen patients (39%) had at least one treatment deferral/delay. Eight patients (24%) required dose reduction. Twenty-four patients (73%) had a drop in PS compare to baseline. Weight loss >5% was observed in 11 patients (34%) during treatment. All patients (100%) experienced grade 1/2 toxicities. Twenty patients (61%) had at least one grade 3/4 toxicity. Commonest grade 3/4 toxicities: neutropenia (n = 10, 30.3%), neutropenic sepsis (n = 3, 9%) diarrhoea (n = 4, 12.1%), fatigue (n = 4, 12.1%) nausea/vomiting (n = 2, 6%) anorexia (n = 2, 6%), oral mucositis (n = 1, 3%) anaemia (n = 1, 3%). Life threatening adverse events included one case of 5FU-related MI, and one patient with bowel perforation. No treatment related deaths occurred. Patients older than 70 had a lower completion rate (28.5% vs. 77%, p = 0.016), higher admission rate (85% vs. 61%, p = 0.228) but similar grade 3/4 toxicity rate (57% vs. 61%, p = 0.832) compared to younger counterparts. Compared to AIO –FLOT4 trial, our patients had higher rates of: discontinuation (33.3% vs. 6%), dose reductions (24% vs. 6%) and serious adverse events (70% vs. 41%). The commonest grade3/4 toxicity was neutropenia in both cohorts, but was less frequent in our institution (30% vs. 52%) probably due to primary GCSF prophylaxis. Grade 3/4 nausea/vomiting was commonest in the AOI-FLOT 4 cohort (12% vs. 6%), while grade3/4 diarrhoea was more frequent in our institution (12% vs. 7%). Fatigue grade 3/4 was commonest in our cohort (12% vs. 9%). No grade 3/4 cases of neurotoxicity were reported in our cohort, compared with the AIO-FLOT4 (8%). Conclusion: Neoadjuvant FLOT for resectable GOA was less tolerable and more toxic in our cohort, with higher rate of early treatment discontinuations, dose reductions, serious adverse events. The above results demonstrate that every day clinical practice often differs from trial results and underscore the importance of reporting real world experience data, especially regarding safety issues.