Table 3.

Management of FOLFIRINOX toxicity.

Toxicity	Management
Neutropenia	Delay chemotherapy until neutrophils ⩾ 1.5 × 109/l; At the next cycle, remove bolus 5-FU and reduce irinotecan to 150 mg/m²; Use G-CSF or pegfilgrastim if febrile neutropenia
Thrombocytopenia	Consider cycle postponement until platelets > 75 × 109/l; At the next cycle, reduce oxaliplatin dose to 60 mg/m² and infusional 5-FU to 25%
Anemia	Evaluate etiology (e.g. cancer-induced inflammation, iron deficiency); Consider red blood cell transfusion; Erythropoietin is poorly efficient in oxaliplatin-induced anemia
Vomiting	Consider FOLFIRINOX as a highly emetogenic regimen and use corticosteroids, an anti-5HT3 antagonist plus anti-NK1 antagonist to prevent acute emesis; prepare outpatient prescription for delayed emesis; patients with diabetes receiving steroids may require regular checks of blood glucose and adjustment of diabetes medication
Grade 3–4 diarrhea	Early diarrhea or abdominal cramps result from hypercholinergic reactions (see below); Delayed diarrhea: use 2 mg of loperamide (two capsules), then 2 mg every 2 h (outpatient supply); see the supplementary appendix of the pivotal study for details;7 At the next cycle, reduce irinotecan dose to 150 mg/m² and remove the bolus 5-FU dose
Sensory neuropathy	At the next cycle, reduce oxaliplatin to 65 mg/m² for grade 3 neurotoxicity and stop oxaliplatin if persistent neurotoxicity occurs between cycles
Transient dysarthric speech, blepharospasm	Use prophylactic subcutaneous atropine 0.25–0.50 mg; Hold infusion until symptoms resolve; Give a warm drink; Check electrolytes levels for hypokalemia; Consider use irinotecan first, then oxaliplatin for next cycles
Laryngo-pharyngeal dysesthesia Laryngo-pseudospasm throat discomfort	Check oxygen saturation: if normal, an anxiolytic may be given; Slow oxaliplatin infusion rate (6 h) and warm drink; Add intravenous calcium gluconate plus magnesium sulphate (1 g of each) in 100 ml of 5DW over 30 min before and after oxaliplatin
Grade 3–4 mucositis	Reduce bolus and infusional 5-FU to 25%
Hypercholinergic reaction with cramping and sweating	Slow infusion rate; Premedicate with subcutaneous atropine 0.25–0.50 mg
Immediate hypersensitivity reactions to oxaliplatin	Refer patient to an allergy unit for skin testing; Slow down the run rate; Consider use of an antihistamine with or without a steroid; Use desensitization protocol using serial dilutions; Possible discontinuation if severe reaction

G-CSF, granulocyte-colony stimulating factor; 5-FU, 5-fluorouracil; 5DW, solution with 5% dextrose in water.