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

Short-term infusional fluorouracil and leucovorin for gastrointestinal cancer (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 D5WΔ 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 D5WΔ 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 topic on "Prevention and treatment 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 topic 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 renal dysfunction
  • A lower starting dose of FU may be needed in patients with impaired liver function.
  • Refer to UpToDate topic 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 renal 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 topic 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.
IV: intravenous; D5W: 5% dextrose in water; NS: normal saline; G-CSF: granulocyte-colony stimulating factors; CBC: complete blood count; WBC: white blood cell; ANC: absolute neutrophil count.
* 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:
  1. Cheeseman SL, et al. Br J Cancer 2002; 87:393.
  2. Hochster HS, et al. J Clin Oncol 2008; 26:3523.
  3. Fluorouracil injection. United States Prescribing Information. US National Library of Medicine. (Available online at dailymed.nlm.nih.gov, accessed on November 30, 2011).
  4. de Gramont A, et al. J Clin Oncol 1997; 15:808.
  5. 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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