Early experience on the histopathological response to perioperative docetaxel, oxaliplatin and 5-FU/Sodium levofolinate (FLOT) for patients with resectable gastric adenocarcinoma when compared to cisplatin/5-fluorouracil (CF)
Authors: A. Rolo, S. Campelos, P. Carvalho, L. Oliveira, B. Lima, A. Teixeira, C. Carvalho, I. Faustino, C. Coutinho
Journal: Annals of Oncology (2018)

Introduction: Gastric cancer is the fifth most common cancer in the Portuguese population, with 3018 new cases/year and an incidence of 13.1 cases/100000. Portugal has one of the highest gastric cancer incidence rate in Europe, particularly Northern Portugal. Perioperative chemotherapy with epirubicin, cisplatin and 5-fluorouracil (ECF) is currently the standard treatment, but CF is an effective alternative with a more favorable toxicity profile. Recently presented at ASCO and ESMO in 2017, perioperative chemotherapy with FLOT significantly improved rates of curative resection, progression-free-survival and overall survival in patients with resectable gastroesophageal adenocarcinoma compared to ECF/X (capecitabine). We aimed to assess whether FLOT would also result in improved outcomes in gastric cancer, when compared to CF. Methods: We retrospectively compared histopathological tumor regression using the Becker and College American of Pathologists (CAP) regression criteria in consecutive patients with resectable gastric cancer (≥ cT2 and/or nodal positive disease) treated at our center in Northern Portugal between January and December of 2017 with FLOT (docetaxel 50 mg/m2, oxaliplatin 85 mg/m2, 5-FU 2600 mg/m2 infusion 24h, sodium levofolinate 100 mg/m2, all in d1, 14/14 days, 4 cycles) or CF (cisplatin 100 mg/m2, d1, 5-FU 1000 mg/m2, d1-d5 28/28 days, 3 cycles) prior to surgical resection. The pathologist was blinded to the chemotherapy regimen. Intention-to-treat statistical analysis was performed, using SPSS. Results: Twenty-six patients were included, 13 in the CF group and 13 in the FLOT group, with a mean age at diagnosis of 55 years (45-81), 81% were male. All patients in the CF group and 12 (92%) in the FLOT group completed all planned preoperative treatment cycles. Two patients (15.4%) in the FLOT group had pathological complete regression (pCR) according to the Becker criteria Tumor Regression Grade (TRG) 1a versus 0% in the CF group (p = 0.182). More patients in the FLOT group obtained complete and subtotal regression (TRG1a/1b) (38.5% vs 7.7% in the CF group, p = 0.16). Finally, the vast majority (76.9%) of the patients in CF group had minor or no regression (TRG3) after neoadjuvant chemotherapy, twice as much as patients in the FLOT group (38.5%). When the CAP system was assessed, FLOT was significantly associated with a higher incidence of pCR (Tumor Regression Score 0 [TRS0]: 15.4% vs 0% in the CF group, p = 0.008), as well as with a significant reduction of partial or poor response/no response in the resected specimen (TRS2/3: 53.8% versus 100% in the CF group, p = 0.015). We found no statistically significant differences in the toxicity profile for both groups prior to surgery. Conclusion: We report on our early experience with the FLOT regimen on a region with a very high incidence of gastric cancer. In our study, perioperative chemotherapy with FLOT was well tolerated, safe, and, crucially, resulted in significantly higher rates of complete histological regression when compared to CF (CAP TRS0: 15.4% versus 0%, p = 0.008). These encouraging results with the FLOT regimen will likely translate into improved clinical outcomes, and could hallmark a change in paradigms in the treatment of patients with gastric adenocarcinoma.