What is the recommended duration of FLOT (fluorouracil, leucovorin, oxaliplatin, docetaxel) neoadjuvant treatment for oesophageal adenocarcinoma?

Duration of FLOT Neoadjuvant Treatment for Oesophageal Adenocarcinoma

The standard FLOT neoadjuvant regimen for oesophageal adenocarcinoma consists of 4 preoperative 2-week cycles (8 weeks total) of docetaxel, oxaliplatin, leucovorin, and fluorouracil. 1

FLOT Regimen Components and Schedule

• FLOT is recognized as the standard of care for perioperative chemotherapy in oesophageal adenocarcinoma 1
• The regimen consists of:
  • Docetaxel 50 mg/m² on day 1
  • Oxaliplatin 85 mg/m² on day 1
  • Leucovorin 200 mg/m² on day 1
  • Fluorouracil 2,600 mg/m² as 24-hour infusion on day 1 1
• Each cycle is administered every 2 weeks 1

Duration of Neoadjuvant Treatment

• The standard duration is 4 preoperative cycles (8 weeks total) before surgery 1
• After surgery, an additional 4 postoperative cycles are typically administered, completing the full perioperative regimen 1, 2
• The FLOT4 trial, which established this regimen as superior to previous standards, used exactly this duration (4 preoperative + 4 postoperative cycles) 2

Evidence Supporting FLOT

• The FLOT4 phase II/III trial demonstrated superior overall survival with FLOT compared to the previous ECF/ECX regimen (median overall survival 50 months vs. 35 months) 2
• FLOT showed better pathologic response rates compared to ECX in patients with locally advanced gastric cancer including oesophagogastric junction adenocarcinomas 1, 2
• The ASCO Expert Panel recognizes FLOT as the standard of care for perioperative chemotherapy in oesophageal adenocarcinoma 1

Alternative Regimens When FLOT Is Not Available

• Where FLOT is not available or feasible, the Expert Panel suggests cisplatin and fluorouracil (CF) or a similar platinum-based regimen 1
• CF regimen: 2 three-weekly cycles of cisplatin (80 mg/m² IV on day 1) and fluorouracil (1 g/m² per day IV on days 1-4) 1

Clinical Considerations

• Intensification of neoadjuvant FLOT to 6 cycles has been studied and appears not to significantly increase perioperative complications, but this is not the standard approach 3
• When choosing between perioperative chemotherapy (FLOT) and neoadjuvant chemoradiotherapy (CROSS), consider:
  • For bulky tumors with proximal extension where complete surgical resection may be challenging, preoperative chemoradiotherapy may be preferred 1
  • For smaller tumors at the gastroesophageal junction without significant proximal extension, perioperative chemotherapy (FLOT) may be preferred 1
• Even after complete clinical tumor response to preoperative chemotherapy, patients with resectable oesophageal adenocarcinoma should proceed to surgery 1

Safety Considerations

• Common grade 3-4 toxicities with FLOT include neutropenia (48.1%), leukopenia (27.8%), diarrhea (14.8%), and fatigue (11.1%) 4
• Close monitoring of hematologic parameters is essential during treatment 4
• Adequate quality and extent of surgery following neoadjuvant therapy should include clear surgical margins and adequate nodal dissection with a goal of obtaining at least 16-18 and preferably 20 lymph nodes 1