Cycle length: 14 days.
Duration of therapy: Treatment is continued until disease progression, unacceptable toxicity, or patient withdrawal. |
| Drug | Dose and route | Administration | Given on days |
| Ramucirumab | 8 mg/kg IV | Dilute with NS to a total volume of 250 mL.*¶ The first dose should be administered over 60 minutes. If tolerated, subsequent infusions may be administered over 30 minutes.[2] | Day 1 |
| Pretreatment considerations: |
| Emesis risk | - MINIMAL (<10%).
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
|
| Prophylaxis for infusion reactions | - Premedicate with an IV H1 receptor antagonist prior to each infusion.[2]
- For patients who have experienced a grade 1 or 2 infusion-related reaction, premedicate with an H1 receptor antagonist, dexamethasone (or equivalent), and acetaminophen prior to each subsequent infusion.[2]
- Refer to UpToDate topics on infusion-related reactions to therapeutic monoclonal antibodies used for cancer therapy.
|
| Baseline liver dysfunction | - Patients with pre-existing Child-Pugh B or C liver dysfunction may develop new-onset or worsening encephalopathy, ascites, or hepatorenal syndrome during treatment with ramucirumab. Use in patients with Child-Pugh B or C cirrhosis only if the potential benefits of treatment are judged to outweigh the risks.
- Refer to UpToDate topics on chemotherapy hepatotoxicity and dose modification in patients with liver disease, molecularly targeted agents.
|
| Cardiovascular issues | - Control hypertension prior to initiating treatment.
- Refer to UpToDate topics on toxicity of molecularly targeted antiangiogenic agents, cardiovascular effects.
|
| Monitoring parameters: |
- Monitor for signs/symptoms of infusion reaction.
|
- CBC with differential, serum electrolytes, and liver and renal function tests at baseline and prior to each treatment cycle.
|
- Prior to each new cycle, assess changes in blood pressure, neurologic symptoms, signs of GI perforation, and risk for bleeding and/or blood clots prior to each treatment. Periodically assess urine protein concentration by dipstick and/or routine urinalysis.
|
- Monitor thyroid function periodically during treatment.
|
| Suggested dose modifications for toxicity: |
| Infusion-related reaction | - Manage symptoms per institutional standards.
- Reduce the infusion rate by 50% for grade 1 to 2 reactions.[2]
- Permanently discontinue for grade 3 to 4 reactions.[2]
|
| Cardiovascular toxicity | - Withhold ramucirumab for severe hypertension until medically controlled.
- Dose adjustment may be needed for ≥grade 2 hypertension.[1]
- Permanently discontinue for medically significant hypertension that cannot be controlled with antihypertensive therapy or hypertensive crisis or hypertensive encephalopathy.
- Refer to UpToDate topics on toxicity of molecularly targeted antiangiogenic agents, cardiovascular effects.
|
| Wound healing | - Withhold ramucirumab for 28 days prior to elective surgery.
- Do not administer ramucirumab for at least 28 days following a major surgical procedure and until the wound is fully healed.
- Discontinue ramucirumab in patients who develop wound healing complications that require medical intervention.
- Refer to UpToDate topics on toxicity of molecularly targeted antiangiogenic agents, non-cardiovascular effects.
|
| Proteinuria | - For urine dipstick 2+ or greater, perform a 24-hour urine collection for protein measurement. Withhold ramucirumab for urine protein ≥2 g over 24 hours. Reinitiate therapy at reduced dose[2] once urine protein returns to <1.5 to 2 g over 24 hours. Permanently discontinue in the setting of nephrotic syndrome.
- Refer to UpToDate topics on toxicity of molecularly targeted antiangiogenic agents, non-cardiovascular effects.
|
| Other toxicity | - Discontinue ramucirumab for serious hemorrhage, arterial thromboembolism, gastrointestinal perforation, or RPLS.[2] Discontinue therapy for a grade 3 or 4 venous thromboembolic event that is considered to be life threatening or that cannot be adequately treated with low-molecular-weight hepatin-based therapy, or that developed during anticoagulant therapy.[1]
- Refer to UpToDate topics on toxicity of molecularly targeted antiangiogenic agents, non-cardiovascular effects and toxicity of molecularly targeted antiangiogenic agents, cardiovascular effects.
|
| If there is a change in body weight of at least 10%, doses should be recalculated. |
