| Cycle length: 5 to 6 weeks (chemoradiotherapy). |
| Drug | Dose and route | Administration | Given on days |
| CapecitabineΔ | 825 mg/m2 by mouth | Twice daily; total daily dose 1650 mg/m2. Swallow whole with water within 30 minutes after a meal, with each dose as close to 12 hours apart as possible. Do not cut or crush tablets.◊ | Daily, 5 days per week (Monday through Friday), during entire 5- to 6-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 | - Lower starting doses of capecitabine may be needed for renal impairment.[2]
- Refer to UpToDate topics on chemotherapy nephrotoxicity and dose modification in patients with renal insufficiency, conventional cytotoxic agents.
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| Monitoring parameters: |
- CBC with differential and platelet count weekly during chemoradiotherapy.
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- Assess electrolytes and liver and renal function weekly during chemoradiotherapy.
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- Monitor for diarrhea, stomatitis, and cutaneous toxicity (palmar-plantar erythrodysesthesias) during treatment.
- Refer to UpToDate topics on cutaneous side effects of conventional chemotherapy agents.
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- Doses of phenytoin and of coumarin-derivative anticoagulants may need to be reduced when either drug is administered concomitantly with capecitabine. More frequent anticoagulant response (INR or prothrombin time) monitoring is necessary for patients receiving concomitant capecitabine and oral coumarin-derivative anticoagulant therapy.
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- Cardiotoxicity observed with capecitabine includes myocardial infarction/ischemia, angina, dysrhythmias, cardiac arrest, cardiac failure, sudden death, electrocardiographic changes, and cardiomyopathy. These adverse reactions may be more common in patients with a prior history of coronary artery disease.
- Refer to UpToDate topics on cardiotoxicity of cancer chemotherapy agents other than anthracyclines, HER2-targeted agents, and fluoropyrimidines.
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| Suggested dose modifications for toxicity: |
| Myelotoxicity | - For neutrophils <1200/microL during therapy, hold capecitabine until ≥1200/microL, then reduce capecitabine to 620 mg/m2 twice daily; if recurs, hold capecitabine until neutrophils ≥1200/microL, then reduce capecitabine to 465 mg/m2 twice daily.[3] For platelet count <75,000/microL during therapy, hold capecitabine until ≥75,000/microL, and reduce subsequent doses of capecitabine to 620 mg/m2 twice daily; if recurs, hold capecitabine until platelet count ≥75,000/microL, and reduce subsequent capecitabine doses to 465 mg/m2 twice daily. 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 capecitabine (620 mg/m2 twice daily).
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| Gastrointestinal toxicity | - Hold capecitabine for grade 2 vomiting (despite antiemetics) or grade 2 or 3 diarrhea or mucositis, and delay reinitiation until ≤grade 1; for first occurrence, reduce capecitabine dose to 620 mg/m2 twice daily; for second occurrence, reduce capecitabine to 465 mg/m2 twice daily; for third occurrence, or any grade 4 diarrhea, or grade 3 or 4 vomiting, or if recovery takes >2 weeks, discontinue capecitabine.[3]
- NOTE: Severe diarrhea, mucositis, and myelosuppression after capecitabine should prompt evaluation for DPD deficiency.
- Refer to UpToDate topics on enterotoxicity of chemotherapeutic agents.
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| Hand-foot syndrome | - For grade 2 or 3 hand-foot syndrome, hold capecitabine until ≤grade 1.[3] Resume capecitabine at 620 mg/m2 twice daily. For second occurrence, hold capecitabine until ≤grade 1, and resume capecitabine at 465 mg/m2 twice daily. For third occurrence or any grade 4 toxicity, discontinue capecitabine.
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| Hepatotoxicity | - For grade 2 transaminase elevation during therapy, hold capecitabine until ≤grade 1; resume capecitabine at 620 mg/m2 twice daily.[3] Patients with grade 3 or 4 hyperbilirubinemia may resume capecitabine once toxicity has reduced to grade ≤2, but at a reduced dose.
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| Other clinically significant adverse events | - For other grade 3 adverse events, hold therapy until ≤grade 1, then resume at a lower dose (620 mg/m2 twice daily); discontinue chemotherapy for grade 4.[3]
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
