Chemotherapy regimens for gastrointestinal cancer: Short-term infusional fluorouracil and leucovorin (modified de Gramont schedule)*^[1,2]

Cycle length: 14 days.
Drug	Dose and route	Administration	Given on days
Leucovorin^¶	400 mg/m² IV	Dilute with 250 mL D5W^Δ and administer over two hours.	Day 1
Fluorouracil (FU)	400 mg/m² IV bolus	Slow IV push over five minutes (administer immediately after leucovorin).	Day 1
FU	2400 mg/m² IV	Dilute in 500 to 1000 mL D5W^Δ and administer over 46 hours (begin immediately after FU IV bolus). To accommodate an ambulatory pump for outpatient treatment, can be administered undiluted (50 mg/mL) or the total dose can be diluted in 100 to 150 mL NS.^Δ	Day 1
Pretreatment considerations:
Emesis risk	LOW. Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
Infection prophylaxis	Primary prophylaxis with G-CSF is not justified (estimated risk of febrile neutropenia <5%^[1,2]). Refer to UpToDate topics on use of granulocyte colony stimulating factors in adult patients with chemotherapy-induced neutropenia and conditions other than acute leukemia, myelodysplastic syndrome, and hematopoietic cell transplantation.
Dose adjustment for baseline liver or kidney dysfunction	A lower starting dose of FU may be needed in patients with impaired liver function. Refer to UpToDate topics on chemotherapy hepatotoxicity and dose modification in patients with liver disease, conventional cytotoxic agents and chemotherapy hepatotoxicity and dose modification in patients with liver disease, molecularly targeted agents.
Monitoring parameters:
CBC with differential and platelet count prior to each treatment.
Assess electrolytes and liver and kidney function prior to each treatment.
Suggested dose modifications for toxicity:
Myelotoxicity	Delay treatment by one week if the total WBC count is <3000/microL, ANC is <1500/microL, or platelets are <100,000/microL. If treatment is delayed for two weeks or delayed for one week on two separate occasions, eliminate the day 1 FU bolus. With the second occurrence, reduce infusional FU by 20%.
Diarrhea	Withhold treatment for grade 2 or worse diarrhea and restart at a lower dose after complete resolution.^[3] NOTE: Severe diarrhea, mucositis, and myelosuppression after FU should prompt evaluation for DPD deficiency. Refer to UpToDate topics on enterotoxicity of chemotherapeutic agents.
Neurologic toxicity	There is no recommended dose for resumption of FU administration following development of hyperammonemic encephalopathy, acute cerebellar syndrome, confusion, disorientation, ataxia, or visual disturbances; the drug should be permanently discontinued.^[3]
Cardiotoxicity	Cardiotoxicity observed with FU includes myocardial infarction/ischemia, angina, dysrhythmias, cardiac arrest, cardiac failure, sudden death, electrocardiographic changes, and cardiomyopathy. There is no recommended dose for resumption of FU administration following development of cardiac toxicity, and the drug should be discontinued.^[3]
If there is a change in body weight of at least 10%, doses should be recalculated.

This table is provided as an example of how to administer this regimen; there may be other acceptable methods. This regimen must be administered by a clinician trained in the use of chemotherapy, who should use independent medical judgment in the context of individual circumstances to make adjustments, as necessary.

ANC: absolute neutrophil count; CBC: complete blood count; D5W: 5% dextrose in water; G-CSF: granulocyte-colony stimulating factors; IV: intravenous; NS: normal saline; WBC: white blood cell.

* This is a modification of the original de Gramont regimen of short-term infusional FU plus leucovorin,^[4] which eliminates the day 2 bolus doses of FU and leucovorin.
¶ Leucovorin dose is given for d,l-racemic mixture.^[5] Use half the dose for LEVOleucovorin (l-leucovorin).
Δ Diluent solutions should not be modified without consulting a detailed reference due to potential incompatibility(ies).

References:

Cheeseman SL, Joel SP, Chester JD, et al. A 'modified de Gramont' regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer. Br J Cancer 2002; 87:393.
Hochster HS, Hart LL, Ramanathan RK, et al. Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study. J Clin Oncol 2008; 26:3523.
Fluorouracil injection. United States Prescribing Information. US National Library of Medicine. (Available online at dailymed.nlm.nih.gov, accessed on November 30, 2011).
de Gramont A, Bosset JF, Milan C, et al. Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with bimonthly high-dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer: a French intergroup study. J Clin Oncol 1997; 15:808.
Leucovorin calcium injection. United States Prescribing Information. US National Library of Medicine. (Available online at dailymed.nlm.nih.gov, accessed on November 30, 2011).

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Chemotherapy regimens for gastrointestinal cancer: Short-term infusional fluorouracil and leucovorin (modified de Gramont schedule)*[1,2]

Chemotherapy regimens for gastrointestinal cancer: Short-term infusional fluorouracil and leucovorin (modified de Gramont schedule)*^[1,2]