| Cycle length: 5 to 6 weeks (chemoradiotherapy). |
| Drug | Dose and route | Administration | Given on days |
| Fluorouracil (FU) | 225 mg/m2 per day IV | Infuse through a central line as a continuous infusion via a portable infusion device. 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 | Daily by continuous infusion five days per week (Monday through Friday) during the entire five- to six-week course of radiation beginning on week 1 |
| Radiotherapy (50.4 Gy) | 1.8 Gy for five days a week | Begin within 24 hours of beginning chemotherapy. | Beginning week 1 and continuing to week 6 |
| Pretreatment considerations: |
| Emesis risk | - LOW.
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
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| Infection prophylaxis | - Primary prophylaxis with G-CSF is not indicated.
- Refer to UpToDate topics on prophylaxis of infection during chemotherapy-induced neutropenia in high-risk adults.
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| Dose adjustment for baseline liver or renal dysfunction | - A lower starting dose of FU may be needed for patients with liver impairment.
- Refer to UpToDate topics on chemotherapy hepatoxicity and dose modification in patients with liver disease.
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| Monitoring parameters: |
- CBC with differential and platelet count weekly during chemoradiotherapy.
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- Assess electrolytes and liver function weekly during chemoradiotherapy.
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- Monitor for diarrhea, stomatitis, and cutaneous toxicity (palmar-plantar erythrodysesthesias) during therapy.
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- More frequent anticoagulant response (INR or prothrombin time) monitoring is necessary for patients receiving concomitant FU and oral coumarin-derivative anticoagulant therapy.
|
| Suggested dose modifications for toxicity: |
| Myelotoxicity | - For neutrophils <1200/microL during therapy, hold FU until ≥1200/microL, then reduce FU to 175 mg/m2 per day; if recurs, hold FU until neutrophils ≥1200/microL, then reduce FU to 125 mg/m2 per day.[2] For platelet count <75,000/microL during therapy, hold FU until ≥75,000/microL, and reduce FU to 175 mg/m2 per day; if recurs, hold FU until platelet count ≥75,000/microL, and reduce FU to 125 mg/m2 per day. If recovery takes >2 weeks, discontinue chemotherapy. For febrile neutropenia or infection with grade 3 or 4 neutropenia, hold chemotherapy until clinical resolution then resume at reduced dose of FU (175 mg/m2 daily).
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| Gastrointestinal toxicity | - Hold FU for grade 2 vomiting or grade 2 or 3 diarrhea or mucositis, and delay reinitiation of treatment until ≤grade 1; for first occurrence, reduce FU to 175 mg/m2 per day; for second occurrence, reduce FU to 125 mg/m2 per day; for third occurrence or any grade 4 diarrhea, or grade 3 or 4 vomiting, or if recovery takes >2 weeks, discontinue FU.[2]
- NOTE: Severe diarrhea, mucositis, and myelosuppression after FU should prompt evaluation for dihydropyrimidine dehydrogenase deficiency.
- Refer to UpToDate topics on enterotoxicity of chemotherapeutic agents.
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| Hepatotoxicity | - For grade 2 hepatotoxicity during therapy, hold FU until bilirubin, alkaline phosphatase, and AST are ≤grade 1; resume FU at 175 mg/m2.[2] Discontinue chemotherapy for grade 3 or 4 hepatotoxicity or if recovery takes >2 weeks.
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| 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]
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| 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]
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| Other clinically significant adverse events | - For other grade 3 adverse events, hold FU until ≤grade 1, then resume at a lower dose (175 mg/m2 per day); discontinue chemotherapy for grade 4.[2]
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
