Total neoadjuvant chemotherapy with FLOT scheme in resectable adenocarcinoma of the gastro-oesophageal junction or gastric adenocarcinoma: impact on pathological complete response and safety

Abstract

Background: Gastric cancer is the fifth cause of cancer incidence worldwide. Multidisciplinary approaches that improve the survival are needed. Perioperative chemotherapies show improvement in pathological complete remission (pCR) and overall survival (OS), but less than 50% of the patients completed the chemotherapeutic regimen. The recent 5-fluorouracil, leucovorin, oxaliplatin, docetaxel-4 (FLOT4) study shows OS 50 months and pCR 16.6%, but only 46% of the patients completed pre-and postoperative treatment. This case series report evaluated pCR and safety in patients that received complete preoperative chemotherapeutic with FLOT.Methods: Patients received eight cycles FLOT regimen before surgery. Each cycle comprised 50 mg/m 2 docetaxel intravenous (iv) on day 1, 85 mg/m 2 oxaliplatin iv on day 1, 200 mg/m 2 leucovorin iv on day 1 and 2,600 mg/m 2 5-fluorouracil iv in a 24-hour infusion on day 1, every 2 weeks.Results: Fifty-nine patients were evaluated, 58 patients received preoperative cycles. Thirty-one patients received all eight cycles of preoperative therapy. 65.5% patients presented any major adverse event. Thirty-nine patients underwent surgery. Thirty-three biopsy reports were obtained. Six patients (18.2%) presented pCR, 13 patients (39.4%) had no lymph node involvement. OS was 21.32 months. Patients with histology of signet ring carcinoma cells had a shorter survival than other histologies. Conclusion:Total neoadjuvant with FLOT chemotherapy presents an adequate safety profile, a similar pathologic regression rate, and a slightly higher rate of completing treatment to report in perioperative FLOT regimen studies. A prospective clinical study with suitable diagnostic, staging tools and an adequate follow-up may prove total neoadjuvant chemotherapy's efficacy.

Exploring FLOT- and FOLFOX-Based total neoadjuvant therapy for patients with locally advanced gastroesophageal cancers

“…Taken together, our results in combination with other recently reported, support the ongoing continued evaluation of TNT in patients with locally advanced GE/G cancer using either FLOT or FOLFOX [28][29][30]. Given that rates of pCR are correlated with recurrence-free survival outcomes, the sum of our experience with FOLFIRINOX, FLOT, and FOLFOX in combination with those from recently reported studies suggests an early indicator that the TNT approach may be effective [25,26,28,31]. However, studies have yet to conclusively determine if survival outcomes can be improved with increased treatment intensity by delivering all chemotherapy prior to CRT and surgery.…”

“…Moreover, 80% (20/25) underwent surgical resection, including 95% R0 resection and 28% pCR with acceptable rates of adverse effects. Taken together, our results in combination with other recently reported, support the ongoing continued evaluation of TNT in patients with locally advanced GE/G cancer using either FLOT or FOLFOX [28][29][30]. Given that rates of pCR are correlated with recurrence-free survival outcomes, the sum of our experience with FOLFIRINOX, FLOT, and FOLFOX in combination with those from recently reported studies suggests an early indicator that the TNT approach may be effective [25,26,28,31].…”

PD-1 blockade enhances chemotherapy toxicity in oesophageal adenocarcinoma

“…Moreover, OAC is an exemplar model of an obesity-driven cancer and as such its incidence is rapidly increasing in parallel with the rising level of obesity 2 . Response rates to the standard of care FLOT (5-fluorouracil (5-FU), oxaliplatin and docetaxel) chemotherapy regimen remain low with a complete pathologic response rate of 16.6% 3 and subsequent clinical outcomes are dismal with a median overall survival rate of 50 months 3 and 5-year overall survival rates as low as 15–40% depending on tumour stage at clinical presentation 4 . Improvements in the efficacy of first-line chemotherapy regimens were achieved through combining immune checkpoint blockade (ICB) with chemotherapy as depicted in the recent findings from the phase III Checkmate 649 trial, which demonstrated the synergy between nivolumab and first-line chemotherapy (FOLFOX and XELOX) in previously untreated oesophagogastric junctional adenocarcinoma (OGJ) patients (n = 1581), in which a significant improvement in overall survival in patients with a PD-L1 combined positive score of 5 or greater was observed (14.4 months (nivolumab plus chemotherapy arm) vs. 11.1 months (chemotherapy arm)) 5 .…”

Perioperative therapy with FLOT4 significantly increases survival in patients with gastroesophageal and gastric cancer in a large real‐world cohort

“…Previous studies reported about the shorter survival of signet cell carcinoma in a neoadjuvant therapy setting. [22][23][24] Indeed, a further interesting subgroup analysis of our cohort showed that only patients with nonsignet cell carcinoma seemed to benefit from perioperative therapy with FLOT4 compared to 5FU/platinum derivative (p for log rank = .005). This benefit was not observed in patients with signet cell carcinoma (P = .375).…”