Usage
- Panitumumab is prescribed for the treatment of metastatic colorectal cancer (mCRC) with wild-type RAS genes. Specifically, it is used in patients whose disease has progressed on or after prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan-based chemotherapy regimens. It is not indicated for use in combination with chemotherapy or for patients with RAS mutations.
- Pharmacological Classification: Monoclonal antibody; antineoplastic agent; epidermal growth factor receptor (EGFR) inhibitor.
- Mechanism of Action: Panitumumab binds with high affinity to the EGFR, blocking the binding of epidermal growth factor and other ligands. This inhibits receptor autophosphorylation and downstream signaling pathways involved in cell growth and proliferation, leading to growth inhibition, apoptosis, and reduced production of vascular endothelial growth factor.
Alternate Names
- International Nonproprietary Name (INN): Panitumumab
- Brand Name: Vectibix®
How It Works
- Pharmacodynamics: Panitumumab exerts its antitumor activity by specifically targeting the EGFR on tumor cells. By binding to EGFR, it inhibits ligand-induced receptor activation, leading to a cascade of downstream effects, including cell growth arrest, apoptosis, and suppression of angiogenesis.
- Pharmacokinetics: Panitumumab exhibits nonlinear pharmacokinetics. It is administered intravenously and distributes to both normal and tumor tissues expressing EGFR. It does not cross the blood-brain barrier. Elimination is primarily through the reticuloendothelial system via receptor-mediated endocytosis and degradation. It has a terminal half-life of approximately 7.5 days (range: 4-11 days).
- Mode of Action: Panitumumab competitively inhibits the binding of ligands to EGFR, preventing receptor dimerization and autophosphorylation. This disrupts downstream signaling cascades, including the RAS/RAF/MAPK and PI3K/Akt pathways, crucial for cell proliferation, survival, and angiogenesis.
- Receptor Binding: Binds specifically and with high affinity to the extracellular domain of EGFR.
- Enzyme Inhibition: Indirectly inhibits downstream kinases involved in cell signaling by preventing EGFR activation.
- Elimination Pathways: Primarily eliminated by the reticuloendothelial system (RES) through receptor-mediated internalization and subsequent lysosomal degradation.
Dosage
Standard Dosage
Adults:
- 6 mg/kg intravenously every 14 days.
- Initial infusion over 60 minutes (for doses ≤ 1000 mg) or 90 minutes (for doses > 1000 mg). Subsequent infusions can be administered over 30-60 minutes if tolerated.
- No loading dose is required.
Children:
- Not established. Panitumumab is not typically used in pediatric patients.
Special Cases:
- Elderly Patients: No specific dose adjustments are routinely recommended for elderly patients. However, individual patient factors should be considered.
- Patients with Renal Impairment: No dose adjustment is necessary.
- Patients with Hepatic Dysfunction: No dose adjustment is necessary.
- Patients with Comorbid Conditions: Carefully assess risks and benefits in patients with a history of interstitial lung disease, pulmonary fibrosis, keratitis, or severe dry eye. Monitor electrolytes during and for 8 weeks after treatment.
Clinical Use Cases
Panitumumab is not indicated for use in the following clinical scenarios:
- Intubation
- Surgical Procedures
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations
Dosage Adjustments
- Infusion Reactions: Reduce infusion rate by 50% for mild reactions. Discontinue immediately and permanently for severe reactions.
- Dermatologic Toxicities: Withhold for severe or intolerable toxicity. May resume at 50% of the dose if toxicity improves.
Side Effects
Common Side Effects
- Skin reactions (rash, acneiform dermatitis, pruritus, dry skin)
- Diarrhea
- Nausea
- Vomiting
- Fatigue
- Constipation
- Abdominal pain
- Paronychia
Rare but Serious Side Effects
- Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)
- Interstitial lung disease/Pulmonary fibrosis
- Infusion reactions (hypersensitivity, anaphylaxis)
- Electrolyte imbalances (hypomagnesemia, hypocalcemia, hypokalemia)
- Ocular toxicities (keratitis, conjunctivitis)
Long-Term Effects
- Potential for long-term skin and nail changes.
- Risk of developing secondary malignancies has not been fully characterized.
Adverse Drug Reactions (ADR)
- See “Rare but Serious Side Effects.”
Contraindications
- Hypersensitivity to panitumumab.
- Known RAS mutations in the tumor.
- Interstitial lung disease or pulmonary fibrosis.
- Concomitant use with bevacizumab-containing chemotherapy.
- Concomitant use with oxaliplatin-containing chemotherapy in patients with mutant RAS mCRC or unknown RAS status.
Drug Interactions
- CYP450 Interactions: No significant CYP450 interactions have been reported.
- Other Interactions: Concomitant use with irinotecan does not appear to affect the pharmacokinetics of either drug. However, combining panitumumab with IFL chemotherapy or bevacizumab-containing chemotherapy can lead to increased toxicity. Combining with oxaliplatin-containing chemotherapy in patients with mutant RAS mCRC shortens overall survival. May reduce the effectiveness of hormonal contraceptives.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Not established. Panitumumab can cause fetal harm and should be avoided during pregnancy. Effective contraception is essential during treatment and for at least 2 months after the last dose.
- Breastfeeding: Panitumumab is excreted in breast milk and may cause serious adverse reactions in breastfed infants. Breastfeeding is contraindicated during treatment and for at least 2 months after the final dose.
Drug Profile Summary
- Mechanism of Action: EGFR inhibitor.
- Side Effects: Skin reactions, diarrhea, fatigue, nausea, vomiting. Serious side effects include severe skin reactions, interstitial lung disease, and infusion reactions.
- Contraindications: Hypersensitivity, RAS mutations, interstitial lung disease/pulmonary fibrosis, concomitant use with bevacizumab or oxaliplatin-containing chemotherapy (in patients with mutant RAS or unknown RAS status).
- Drug Interactions: Increased toxicity with IFL or bevacizumab-containing chemotherapy; reduced efficacy of hormonal contraceptives.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: 6 mg/kg IV every 14 days.
- Monitoring Parameters: Monitor electrolytes, skin, and respiratory status.
Popular Combinations
Panitumumab is typically used as a single agent. It is not recommended in combination with chemotherapy due to increased toxicity and decreased survival in certain populations.
Precautions
- General Precautions: Monitor for dermatologic toxicities, infusion reactions, and electrolyte imbalances. Pre-screening for RAS mutation status is essential.
- Specific Populations: See “Dosage - Special Cases” and “Pregnancy and Breastfeeding.”
- Lifestyle Considerations: Limit sun exposure. Advise against driving or operating machinery if vision or concentration are affected.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Panitumumab?
A: 6 mg/kg intravenously every 14 days.
Q2: How is Panitumumab administered?
A: Intravenous infusion.
Q3: What are the most common side effects of Panitumumab?
A: Skin reactions (rash, acneiform dermatitis), diarrhea, fatigue, nausea, vomiting.
Q4: What are the contraindications to using Panitumumab?
A: Hypersensitivity to panitumumab, known RAS mutations, interstitial lung disease, concomitant use with bevacizumab-containing chemotherapy.
Q5: Can Panitumumab be used during pregnancy or breastfeeding?
A: No, Panitumumab is contraindicated during pregnancy and breastfeeding.
Q6: How does Panitumumab work?
A: It is a monoclonal antibody that binds to EGFR, inhibiting cell growth and proliferation.
Q7: Should Panitumumab be used with chemotherapy?
A: No, it is generally not recommended for use in combination with chemotherapy due to increased toxicity or reduced efficacy.
Q8: What should I monitor in patients receiving Panitumumab?
A: Monitor for skin reactions, electrolyte imbalances, and signs of pulmonary toxicity. Regular blood tests are recommended.
Q9: Is there a specific patient population where Panitumumab is not indicated?
A: Patients with RAS mutations in their tumor.
