What is FLOT (Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel) chemotherapy?

FLOT Chemotherapy Regimen in Gastric Cancer

FLOT is a chemotherapy regimen consisting of Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel used primarily in the treatment of gastric and gastroesophageal junction adenocarcinoma. 1

Components and Administration

• FLOT consists of four specific medications administered in a defined schedule:

  • Docetaxel (50 mg/m²) on day 1 2
  • Oxaliplatin (85 mg/m²) on day 1 2
  • Leucovorin (200 mg/m²) on day 1 2
  • Fluorouracil (2600 mg/m²) as a 24-hour infusion on day 1 2

• The regimen is typically administered every 2 weeks in a biweekly schedule 2

Clinical Applications

• FLOT is primarily used as perioperative chemotherapy (both before and after surgery) for patients with locally advanced, resectable gastric cancer or gastroesophageal junction adenocarcinoma 3

• The standard perioperative FLOT protocol consists of:

  • 4 preoperative cycles (8 weeks of treatment) 3
  • Surgical resection 3
  • 4 postoperative cycles (8 weeks of treatment) 3

• FLOT can also be used in metastatic gastric cancer settings, though its efficacy varies compared to other regimens in this context 4

Efficacy

• The landmark FLOT4 trial demonstrated that perioperative FLOT significantly improved overall survival compared to the previous standard ECF/ECX regimen (median overall survival 50 months vs. 35 months) 3

• FLOT showed an objective response rate of 57.7% in patients with metastatic disease, with a median time to treatment response of 1.54 months 2

• In metastatic disease, median progression-free survival with FLOT is approximately 5.2 months and overall survival about 11.1 months 2

• Approximately 25% of patients experience prolonged (>12 months) progression-free survival on FLOT therapy 2

Toxicity Profile

• Common grade 3-4 adverse events with FLOT include:

  • Neutropenia (48.1%) 2
  • Leukopenia (27.8%) 2
  • Diarrhea (14.8%) 2
  • Fatigue (11.1%) 2

• Febrile neutropenia occurs in approximately 8% of patients 5

• Complicated neutropenia is relatively rare, occurring in about 3.8% of patients 2

• Treatment-related mortality is approximately 2.6% 5

Regional Variations in Usage

• While FLOT has become a standard in Western countries, its adoption varies in Asian countries 4

• In Asia, the FLOT regimen has not been widely developed as it was not shown to be superior to FLO (Fluorouracil, Leucovorin, Oxaliplatin) in patients with metastatic gastric cancer or in elderly patients (≥70 years) 4

• Chinese studies have shown that FLOT as preoperative chemotherapy may be superior to initial surgery followed by chemotherapy for resectable locally advanced gastric cancer 6

Alternative Regimens

• For patients who cannot tolerate FLOT, alternative regimens include:
  • ECF (Epirubicin, Cisplatin, Fluorouracil) 1
  • FOLFOX (Fluorouracil, Leucovorin, Oxaliplatin) 1
  • XELOX/CAPOX (Capecitabine, Oxaliplatin) 1
  • SOX (S-1, Oxaliplatin) 1
  • FOLFIRI (Fluorouracil, Leucovorin, Irinotecan) for patients unable to tolerate platinum-based therapy 1

Modified FLOT Regimens

• Modified FLOT regimens with dose adjustments have been developed to improve tolerability while maintaining efficacy 5

• DOF (Docetaxel, Oxaliplatin, and 5-Fluorouracil) is a variation that omits leucovorin while maintaining similar efficacy 7

Clinical Considerations

• Completion rates for the full perioperative FLOT protocol (both pre- and post-operative) are approximately 77%, indicating good feasibility in clinical practice 5

• Dose modifications are often required due to toxicity, but this doesn't necessarily compromise efficacy 5

• FLOT should be used with caution in elderly patients, as it has not shown superior efficacy to simpler regimens in this population 4