Neoadjuvant, perioperative and palliative treatment

Synopsis

Choose systemic or chemoradiation treatment by histology, site, stage, biomarkers and fitness, deliver a defined specialist regimen safely, and integrate palliation of dysphagia and nutrition.

Neoadjuvant treatment is given before surgery to treat micrometastatic disease, test biology and improve resection; perioperative therapy includes planned pre- and postoperative components.
The Thames Valley January 2025 v5.1 FLOT example is for fit PS 0–1 adults with resectable gastric or junctional adenocarcinoma: four 14-day cycles before surgery and, only after recovery and review, four after surgery.
Day 1 gives docetaxel 50 mg/m² IV over 60 minutes in sodium chloride 0.9%, calcium folinate 350 mg with oxaliplatin 85 mg/m² in glucose 5% over 2 hours, then fluorouracil 2600 mg/m² by continuous IV infusion over 24 hours; GCSF starts at least 24 hours later.

Key red flags

A temperature or acute illness during cytotoxic treatment is neutropenic sepsis until urgently assessed, even if the most recent neutrophil count was normal.

Fluoropyrimidine-associated chest pain can represent coronary vasospasm or myocardial injury and requires immediate treatment interruption and cardiac assessment.

Neutropenic illness

Fever, rigors, hypotension or sudden deterioration during chemotherapy requires emergency sepsis assessment.

Fluoropyrimidine cardiac symptoms

New chest pain during or shortly after fluorouracil infusion requires immediate interruption and cardiac evaluation.

Reasoning priorities

FLOT pretreatment blood count and organ review

Confirm eligibility for each cycle of this specialist protocol.

Check FBC, U&E, LFTs, creatinine, weight and toxicity every cycle. Require neutrophils at least 1.5 × 10⁹/L and platelets at least 100 × 10⁹/L; below either threshold delay treatment. If both recover within 2 weeks the local protocol resumes 100% dose; otherwise the consultant decides the specified reductions. With CrCl below 30 mL/min, pause cycle authorisation for consultant-led oxaliplatin reduction; v5.1 says consider 50% of the original dose. Deteriorating liver function requires consultant review before proceeding: bilirubin above 50 micromol/L may require stopping or changing treatment, and fluorouracil is not recommended above 85 micromol/L.

Worked reasoning

Worked case: perioperative FLOTDeliver the preoperative component and reassess

A fit 55-year-old with resectable gastric adenocarcinoma has normal DPD testing, adequate marrow, renal and hepatic function, and an MDT plan for perioperative FLOT followed by gastrectomy.

Confirm PS 0–1, baseline DPYD result, FBC, U&E, LFTs, creatinine, weight, nutrition and central access. Give dexamethasone 8 mg by mouth twice daily from 24 hours before treatment, or 20 mg IV on chemotherapy day if that was not taken, then 8 mg twice daily for 2 days after chemotherapy.
Each 14-day cycle gives docetaxel 50 mg/m² in sodium chloride 0.9% over 60 minutes, calcium folinate 350 mg and oxaliplatin 85 mg/m² concurrently in glucose 5% over 2 hours, then fluorouracil 2600 mg/m² continuously over 24 hours; start GCSF at least 24 hours after chemotherapy. Four preoperative cycles are delivered with counts above protocol thresholds.
Restaging CT shows no new metastasis and the patient retains operative fitness, so the MDT confirms gastrectomy rather than continuing chemotherapy without the planned source operation.
After R0 resection, review healing, pathology, performance status, neuropathy and marrow, renal and hepatic recovery; the patient is fit to begin the planned four postoperative cycles, with a fresh proceed/hold decision before each cycle.

Key medicines

Thames Valley Cancer Alliance perioperative FLOT v5.1 (January 2025 specialist example)For a fit PS 0–1 adult, give four cycles before surgery and, subject to postoperative recovery and review, four cycles afterwards. Every 14 days on day 1: docetaxel 50 mg/m² IV in sodium chloride 0.9% over 60 minutes; calcium folinate 350 mg IV and oxaliplatin 85 mg/m² IV concurrently in glucose 5% over 2 hours; then fluorouracil 2600 mg/m² by continuous IV infusion over 24 hours. Dexamethasone is 8 mg by mouth twice daily from 24 hours before chemotherapy, or 20 mg IV on the treatment day, followed by 8 mg twice daily for 2 days; start GCSF at least 24 hours after chemotherapy.Confirm DPYD status, PS 0–1, FBC, U&E, LFTs, creatinine and weight. Require neutrophils at least 1.5 × 10⁹/L and platelets at least 100 × 10⁹/L; otherwise delay. If both recover within 2 weeks, the local protocol resumes 100% dose. If they do not, the consultant reviews treatment; the protocol specifies no more than 75% oxaliplatin and docetaxel, while fluorouracil is maintained unless platelets are below 10 × 10⁹/L and neutrophils below 0.5 × 10⁹/L. Use glucose-compatible administration for oxaliplatin and folinate. Stop and assess fever, severe diarrhoea or mucositis, progressive neuropathy, hypersensitivity, pump failure or chest pain; a negative DPD test does not remove serious fluoropyrimidine risk. Before authorising the next cycle, refer CrCl below 30 mL/min for consultant-led oxaliplatin dose reduction; this local protocol says consider 50% of the original dose. Refer any deteriorating hepatic function for consultant review; bilirubin above 50 micromol/L may indicate progression and require cessation or a regimen change, while fluorouracil is not recommended when bilirubin exceeds 85 micromol/L. Do not proceed with unchanged FLOT while these decisions are pending. The docetaxel hepatic table refers to a 100 mg/m² starting dose: its 75 mg/m² entry must not be substituted for this regimen's 50 mg/m² dose.

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