| Cycle length: 21 days. |
| Drug | Dose and route | Administration | Given on days |
| Bevacizumab | 7.5 mg/kg IV | Dilute into a total volume of 100 mL NS.* Administer the first dose over 90 minutes. If well tolerated, the second infusion may be administered over 60 minutes. If well tolerated, all subsequent doses may be administered over 10 to 30 minutes. | Day 1 |
| Capecitabine¶ | 1000 mg/m2 per dose by mouth | Twice daily (total dose 2000 mg/m2 daily). 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.Δ | Days 1 to 14 |
| Pretreatment considerations: |
| Emesis risk | - Capecitabine: LOW (10 to 30%).
- Bevacizumab: MINIMAL (<10%).
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
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| Prophylaxis for infusion reactions | - There is no standard premedication regimen.
- Refer to UpToDate topics on infusion-related reactions to therapeutic monoclonal antibodies used for cancer therapy.
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| Vesicant/irritant properties | - Bevacizumab is neither a vesicant nor an irritant.
- Refer to UpToDate topics on extravasation injury from chemotherapy and other non-antineoplastic vesicants.
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| Infection prophylaxis | - Primary prophylaxis with G-CSF not indicated (reported rate of any grade neutropenia was 5% in the original study[1]).
- 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 | - Bevacizumab does not require dosage adjustments for liver or renal dysfunction. Lower starting doses of capecitabine may be needed for patients with renal impairment.
- 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 at baseline then every three weeks prior to each treatment.
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- Assess electrolytes, liver, and renal function at baseline then every three weeks prior to each treatment.
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- Assess changes in blood pressure, urine protein concentration, neurologic function, signs of GI perforation, and risk for bleeding and/or blood clots prior to each treatment.
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- 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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- Monitor for diarrhea and palmar-plantar erythrodysesthesia during treatment.
- Refer to UpToDate topics on cutaneous side effects of conventional chemotherapy agents.
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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 | - The treatment cycle should be delayed one week if the total WBC count is <3000/microL, absolute neutrophil count is <1500/microL, or the platelet count is <75,000/microL on day 1. If treatment is delayed for two weeks or delayed for one week on two separate occasions, reduce dose of capecitabine. For grade 4 neutropenia or thrombocytopenia of febrile neutropenia during therapy, interrupt capecitabine until resolves to grade 0 or 1, then reduce dose by 25% for the next treatment.[2]
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| Nonhematologic toxicity (including hepatotoxicity) | - In the original protocol, dose modifications of capecitabine were allowed for the occurrence and resolution of any NCI-CTC grades 2 to 4 nonhematologic toxicity during the prior cycle.[1] For grade 2 or higher toxicity, interrupt capecitabine until resolved to grade 0 or 1.
- Recommended dose modification guidelines for capecitabine based upon toxicity are available in the United States Prescribing Information.[2]
- Grade 2: For the first, second, and third occurrence, hold capecitabine therapy. After resolution to grade 1 or less, resume treatment (first occurrence, no dosage adjustment; second occurrence, 75% of the starting dose; third occurrence, 50% of the starting dose).[2] For the fourth occurrence of a grade 2 toxicity, discontinue capecitabine therapy.
- Grade 3: For the first and second occurrence, hold capecitabine therapy. After resolution to grade 1 or less, resume treatment at a reduced dose (first occurrence, 75% of the starting dose; second occurrence, 50% of the starting dose). For the third occurrence of a grade 3 toxicity, discontinue capecitabine therapy.
- Grade 4: Discontinue capecitabine therapy. Alternatively, hold capecitabine therapy, and begin next treatment at 50% of the starting dose when toxicity resolves to grade 1 or less; discontinue treatment for fist recurrence of grade 4 toxicity.
- Patients with grade 3 or 4 hyperbilirubinemia may resume capecitabine once toxicity has reduced to grade ≤2, but at a reduced dose.
- Doses of capecitabine that are omitted for toxicity are not replaced. The patient should resume planned treatment cycles at the modified dose.
- NOTE: Severe diarrhea, mucositis, and myelosuppression after initiation of capecitabine should prompt evaluation for DPD deficiency.
- Refer to UpToDate topics on enterotoxicity of chemotherapeutic agents.
- Discontinue bevacizumab for hypertensive crisis or hypertensive encephalopathy, serious hemorrhage, arterial thromboembolism, nephrotic syndrome, gastrointestinal perforation, fistula formation, or RPLS.[3] Bevacizumab should not be administered within 28 days of surgery, and it should be suspended prior to elective surgery.
- Refer to UpToDate topics on toxicity of molecularly targeted antiangiogenic agents, non-cardiovascular effects and toxicity of molecularly targeted antiangiogenic agents, cardiovascular effects.
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
