A perioperative chemotherapy regimen used for resectable gastric and gastroesophageal junction (GEJ) adenocarcinoma, designed to improve survival compared to older regimens like ECF/ECX or EOX.
FLOT Components (every 2 weeks):
- F: 5-Fluorouracil (5-FU) – antimetabolite, inhibits thymidylate synthase → impaired DNA synthesis.
- L: Leucovorin (folinic acid) – enhances binding of 5-FU to thymidylate synthase, boosting efficacy.
- O: Oxaliplatin – platinum compound, crosslinks DNA.
- T: Docetaxel – taxane, stabilizes microtubules → mitotic arrest.
Typical Schedule (q2wks, 4 cycles pre-op + 4 cycles post-op)
- Docetaxel 50 mg/m² IV day 1
- Oxaliplatin 85 mg/m² IV day 1
- Leucovorin 200 mg/m² IV day 1
- 5-FU 2600 mg/m² continuous infusion over 24 h day 1
Clinical Use
- Standard of care for locally advanced, resectable gastric/GEJ adenocarcinoma (perioperative).
- Shown in the FLOT4 trial to improve overall survival and progression-free survival compared to ECF/ECX.
Key Toxicities
- Docetaxel: neutropenia, mucositis, alopecia, neuropathy, fluid retention.
- Oxaliplatin: peripheral neuropathy (acute cold-induced + cumulative), cytopenias.
- 5-FU: mucositis, diarrhea, myelosuppression, cardiotoxicity (rare).
- Leucovorin: minimal toxicity (enhancer only).
Pharmacist Considerations
- Requires growth factor support in many patients (risk of neutropenia).
- Monitor for neurotoxicity (oxaliplatin) and GI toxicities (5-FU).
- Pre/post-operative timing is key → 4 cycles before surgery and 4 cycles after, if tolerated.
- Dose adjustments in renal/hepatic impairment may be needed.
- Supportive care: antiemetics, G-CSF, mouth care for mucositis, loperamide for diarrhea.
Summary:
FLOT = 5-FU + Leucovorin + Oxaliplatin + Docetaxel, a perioperative gastric/GEJ cancer regimen, more effective than ECF/EOX, but with significant toxicity requiring close monitoring and supportive care.
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