Cycle length: 8 weeks.
Duration of therapy: Maximum of 4 cycles (adjuvant setting). |
| Drug | Dose and route | Administration | Given on days |
| Leucovorin* | 500 mg/m2 IV | Dilute leucovorin with 250 mL D5W¶ and administer over two hours. | Days 1, 8, 15, 22, 29, 36 |
| Fluorouracil (FU) | 500 mg/m2 IV | Administer one hour after the start of the leucovorin infusion. Drug is available in 50 mg/mL solution that needs no further dilution prior to administration as slow IV push over five minutes. | Days 1, 8, 15, 22, 29, 36 |
| Pretreatment considerations: |
| Emesis risk | - LOW.
- Refer to UpToDate topics on prevention and treatment of chemotherapy-induced nausea and vomiting in adults.
|
| Infection prophylaxis | - The exact incidence of febrile neutropenia is not reported with this regimen; however, only 4% of patients had grade 3 or 4 neutropenia. Primary prophylaxis with G-CSF is not routinely indicated but use should be individualized according to current guidelines.
- 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 liver or renal dysfunction | - A lower starting dose of FU may be needed for patients with liver impairment.
- 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: |
- Obtain CBC with differential and platelet count weekly during treatment.
|
- Assess electrolytes, renal and liver function monthly during treatment.
|
- Monitor for diarrhea and cutaneous toxicity (palmar-plantar erythrodysesthesias).
|
| Suggested dose modifications for toxicity: |
| Myelotoxicity | - Hold treatment for ANC <1000/microL or platelet count <100,000/microL. In the original protocol (which used a higher dose of FU, 600 mg/m2 per week),[2] the FU dose was decreased by 100 mg/m2 if the WBC on the day of treatment was <4000/microL or the platelet count was <100,000/microL.[1]
|
| Renal toxicity | - Prior to therapy, patients are required to have a serum creatinine of less than three times the ULN.[1]
|
| Gastrointestinal toxicity | - Interruption of therapy and/or dose reduction of FU may be necessary for gastrointestinal toxicity. Patients who develop diarrhea should be closely monitored and supportive care measures (eg, fluid and electrolyte replacement, loperamide, etc) provided as needed. For grade 2 or worse diarrhea, treatment should be withheld until resolution of diarrhea for at least 24 hours without anti-diarrheal medication. In the original protocol,[2] the occurrence of grade 1 stomatitis, diarrhea, or vomiting prompted a decrease in the FU dose by 100 mg/m2 for all future doses.
- NOTE: Severe diarrhea, mucositis, and myelosuppression after FU should prompt evaluation for DPD deficiency.[3]
- Refer to UpToDate topics on enterotoxicity of chemotherapeutic agents.
|
| Palmar-plantar erythrodysesthesia | - In the original protocol,[2] for grade 2 or higher skin rash, treatment was withheld until recovery.
- Refer to UpToDate topics on cutaneous complications of conventional chemotherapy 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. |
