Chemotherapy protocol Drug regimen FLOT (5FU, Folinic acid, Oxaliplatin, Docetaxel)

Indications for use Adenocarcinoma stomach or gastro-oesophageal junction type I to IV; perioperative chemotherapy ECOG PS: 0-1

Regimen DRUG FLUID TIME Docetaxel 50mg/m2 IV 250ml 0.9% sodium chloride 1 hr Oxaliplatin 85mg/m2 IV 500ml 5% Glucose 2 hrs Folinic acid 350mg IV 250ml 5% Glucose 2 hrs 5-Fluorouracil 2600mg/m2 IV Infusion pump 24 hrs

Dexamethasone 8mg 12 hourly for 3 days, starting 24 hours before chemotherapy Regimen to be given 2 weekly (4 cycles before surgery and 4 cycles after)

Investigations prior to initiating treatment FBC U&Es LFTs CT scan 2D ECHO

Cautions Ensure bilirubin is <= 1.5 x ULN AST/ALT < 3.5 x ULN Oxaliplatin should always be administered before fluoropyrimidines Avoid cold drinks for 2-3 days after Chemotherapy EF > 50% by 2D ECHO

Investigations and consultations prior to each cycle FBC, U&Es, LFTs The liver function test may be retrospectively looked at (i.e. after the chemotherapy treatment) unless they are known to be abnormal then they need to be repeated the day before so that the results are available pre-chemotherapy. Consultation prior to each cycle needed unless specified otherwise.

Acceptable levels for treatment to proceed (if outside these delay one week or contact consultant) Acceptable blood range: Neutrophils 1.5, platelets 100, Hb  9.5 If Neutrophils 1.0 – 1.5 contact consultant If U&E/LFT abnormal check with consultant

Side Effects Myelosuppression, alopecia, mucositis, diarrhoea, neurotoxicity, allergic reactions, coronary artery spasm, palmar/plantar erythema, nausea, vomiting, stomatitis, loss of appetite, fatigue, renal impairment, infection, ovarian failure/infertility, auditory impairment Dihydropyrimidine dehydrogenase (DPD) deficiency can result in severe toxicity secondary to reduced fluorouracil metabolism- avoid use in patients with known DPD deficiency.

Dose modification criteria

Neutropenia 1st occurrence of febrile neutropenia -> add GCSF for next cycle 2nd occurrence of febrile neutropenia after adding GCSF -> Reduce Docetaxel AND Oxaliplatin to 75% dose 3rd occurrence of febrile neutropenia after dose reduction -> Reduce Docetaxel AND Oxaliplatin to 50% dose

Thrombocytopenia If thrombocytopenia leading to bleeding, reduce dose of Docetaxel AND Oxaliplatin to 75% If further thrombocytopenia related bleeding episodes, reduce Docetaxel and Oxaliplatin to 50% dose

Renal impairment Creatinine clearance < 30: Omit Oxaliplatin, Reduce 5FU dose to 80% -> Check with consultant for possible deferral

Hepatic impairment ALT/AST >3.5xULN – omit Docetaxel & 5FU ->Check with consultant for possible deferral Bilirubin > ULN – omit Docetaxel; consider 50% dose reduction for 5FU -> check with consultant for possible deferral

Diarrhoea If diarrhoea G-I: Loperamide Diarrhoea >= G-II: Loperamide -> discuss with consultant for dose reduction For G II toxicity and above, reduce all (5FU, Oxaliplatin, Docetaxel) to 75% dose and if recurs then reduce to 50% dose.

Neurological toxicity For G-II neuropathy, reduce Docetaxel and Oxaliplatin to 75% dose For G-III neuropathy, discuss with consultant about deferral and dose reduction to 50% dose

Toxicity Duration of toxicity Duration of toxicity Persistent between 1-7 days >7 days cycles Cold-related No reduction No reduction Withhold chemo dysesthesia until recovery then restart at 75% dose for Oxaliplatin and Docetaxel

Paraesthesia without No reduction No reduction Withhold chemo pain until recovery then restart at 75% dose for Oxaliplatin and Docetaxel

Paraesthesia with No reduction Reduce to 75% dose Omit Oxaliplatin and pain or functional on subsequent cycles Docetaxel and impairment and discuss with discuss with consultant consultant

Omit Oxaliplatin and Docetaxel if recurs Acute laryngopharyngeal dysesthesia If during or soon after Oxaliplatin infusion then increase duration to 6 hrs; If it occurs during Docetaxel infusion, treat as per anaphylactic reaction

Specific information on administration: Patient needs central line insertion. DO NOT mix Oxaliplatin with 0.9% sodium chloride or any chloride containing solution. Oxaliplatin in 5% Glucose and Folinic acid in 5% Glucose can be administered concurrently using a Y-line BUT NOT IN SAME bag. Flush the line with 5% Glucose after Oxaliplatin before starting next drug. Loperamide as 4mg stat and then 2mg following each loose stool (Max 16mg / 8 caps in 24 hrs).

THIS PROTOCOL HAS BEEN DIRECTED BY DR MITCHELL LEAD CLINICIAN FOR UPPER GI CANCER

RESPONSIBILITY FOR THIS PROTOCOL LIES WITH THE HEAD OF SERVICE

DATE November 2017 REVIEW November 2019 VERSION 2