| Cycle length: 28 days. |
| Drug | Dose and route | Administration | Given on days |
| Panitumumab | 6 mg/kg IV | Dilute to total volume 100 mL¶ with NSΔ and administer over 60 minutes◊ using a low-protein-binding 0.2 micron or 0.22 micron in-line filter. | Days 1 and 15 |
| Irinotecan | 180 mg/m2 IV§ | Dilute in 500 mL D5WΔ and administer over 90 minutes (can be administered concurrently with leucovorin via y-site connection) after panitumumab. | Days 1 and 15 |
| Leucovorin¥ | 400 mg/m2 IV | Dilute in 250 mL D5WΔ and administer over two hours; may give concurrent with irinotecan via y-site connection. | Days 1 and 15 |
| Fluorouracil (FU), bolus | 400 mg/m2 IV | Slow IV push over five minutes (administer immediately after leucovorin). | Days 1 and 15 |
| FU, infusional | 2400 mg/m2 IV | Dilute in 500 to 1000 mL D5WΔ and administer over 46 hours (begin immediately after FU bolus). 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 | Days 1 and 15 |
| Pretreatment considerations: |
| Emesis risk | - MODERATE (30 to 90% frequency of emesis).
- Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
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| Prophylaxis for infusion reactions | - Routine premedication not indicated.
- Refer to UpToDate topics on infusion-related reactions to therapeutic monoclonal antibodies used for cancer therapy.
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| Infection prophylaxis | - Primary prophylaxis with G-CSF is not justified (risk of febrile neutropenia with this regimen was 2%[1]).
- 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.
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| Dose adjustment for baseline liver or renal dysfunction | - A lower starting dose of FU and irinotecan may be needed for patients with baseline hepatic impairment. A lower starting dose of irinotecan may be needed for patients with severe renal impairment.
- Refer to UpToDate topics on chemotherapy hepatotoxicity and dose modification in patients with liver disease, conventional cytotoxic agents; chemotherapy hepatotoxicity and dose modification in patients with liver disease, molecularly targeted agents; and chemotherapy nephrotoxicity and dose modification in patients with renal insufficiency, conventional cytotoxic agents.
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| Diarrhea | - Irinotecan is associated with early and late diarrhea, both of which may be severe. For patients who develop abdominal cramps and/or diarrhea within 24 hours of treatment, administer atropine (0.3 to 0.6 mg IV) and premedicate with atropine during later cycles. Patients must be instructed in the early use of loperamide as a treatment for late diarrhea.
- NOTE: Severe diarrhea, mucositis, and myelosuppression after FU should prompt evaluation for DPD deficiency.
- Refer to UpToDate topics on enterotoxicity of chemotherapeutic agents.
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| Monitoring parameters: |
- Obtain CBC with differential and platelet count prior to each treatment.
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- Assess electrolytes (including magnesium, calcium, and potassium) and liver and renal function prior to each dose. Monitor serum calcium, magnesium, and potassium levels weekly for eight weeks after completion of therapy.[2]
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- Patients who develop diarrhea should be closely monitored and supportive care measures (eg, fluid and electrolyte replacement, loperamide, antibiotics, etc) provided as needed. Do not retreat until resolution of diarrhea for at least 24 hours without antidiarrheal medication.
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- Monitor for skin rash and for evidence of keratitis or ulcerative keratitis.
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- Monitor for signs or symptoms of pulmonary toxicity.
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| Suggested dose modifications for toxicity: |
| Myelotoxicity | - Delay treatment until ANC is >1500/microL and the platelet count is >100,000/microL. United States Prescribing Information suggests irinotecan dose reduction for grade 2 or worse hematologic toxicity during a prior cycle.[3]
- A different approach is used by some clinicians. If treatment is delayed for two weeks or delayed for one week on two separate occasions, the day 1 FU bolus is eliminated. With the second occurrence, reduce the FU infusion dose by 20% and reduce irinotecan dose to 150 mg/m2.
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| Diarrhea | - Withhold treatment until resolution of diarrhea for at least 24 hours off antidiarrheal medications. Reduce irinotecan dose for patients with grade 2 or worse diarrhea during a prior treatment cycle.[3]
- Refer to UpToDate topics on enterotoxicity of chemotherapeutic agents.
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| Dermatologic toxicity | - Severe dermatologic reactions, such as acneiform rash, require delayed administration of panitumumab and/or dose reduction.
- Refer to UpToDate topics on acneiform eruption secondary to epidermal growth factor receptor (EGFR) inhibitors.
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| Pulmonary toxicity | - Permanently discontinue panitumumab in patients developing pulmonary fibrosis/interstitial lung disease.[2]
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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.[4]
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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.[4]
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| Other toxicity | - For other nonhematologic toxicities, if grade 2, hold treatment until ≤grade 1; if grade 3 or 4, hold treatment until ≤grade 2.[2,3] Withhold FU for grade 2 or worse diarrhea, and restart at a lower dose after complete resolution.[4] Reduce irinotecan dose for patients with grade 2 or worse other nonhematologic toxicities during a prior treatment cycle except for alopecia, anorexia, or asthenia.[3] For grade 3 mucositis, eliminate FU bolus dose; prophylactic ice chips may be beneficial.
- Refer to UpToDate topics on oral toxicity associated with chemotherapy.
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| If there is a change in body weight of at least 10%, doses should be recalculated. |
