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panitumumab (Vectibix)

Indications: - EGFR-expressing metastatic colorectal carcinoma with disease progression on or following chemotherapy with fluorouracil, oxaliplatin, irinotecan - head & neck cancer - lung cancer [3] Contraindications: - mutant KRAS codon 12 or 13 [4] Dosage: 1) adults 6 mg/kg IV over 1 hour every 14 days 2) infuse doses of > 1000 mg over 90 minutes Single use vials: 5, 10, 20 mL, constitute to 20 mg/mL Monitor: 1) serum Ca+2, serum Mg+2 2) avoid sunlight Adverse effects: 1) skin rash, paronychia, photosensitivity 2) hypomagnesemia, hypocalcemia 3) nausea, diarrhea abdominal pain, constipation 4) fatigue 5) severe dermatologic toxicities with possible infection - MAY BE FATAL 6) infusion reactions 7) pulmonary fibrosis 8) hypersensitivity Drug interactions: 1) convurrent irinotecan, bolus 5-fluorouracil, leucovorin not recommended Laboratory: - test for EGFR expression - test for KRAS mutations [4] Mechanism of action: 1) human IgG2 kappa monoclonal antibody against EGFR 2) competitive inhibition of EGFR - prevents autophosphorylation, activation & internalization of EGFR 3) inhibits cell growth 4) induces apoptosis 5) decreases pro-inflammatory cytokines 6) decreases vascular growth factors 7) inactive in colorectal cancer patients with KRAS mutations [4] Notes: Amgen

Interactions

drug adverse effects of tyrosine kinase inhibitor(s)

General

antineoplastic monoclonal antibody EGF receptor (EGFR) inhibitor

References

  1. Monthly Prescribing Reference, Nov 2006
  2. Patil DT, Fraser CR, Plesec TP. KRAS testing and its importance in colorectal cancer. Curr Oncol Rep. 2010 May;12(3):160-7. PMID: 20425075 - Tol J, Punt CJ. Monoclonal antibodies in the treatment of metastatic colorectal cancer: a review. Clin Ther. 2010 Mar;32(3):437-53. PMID: 20399983
  3. Medical Knowledge Self Assessment Program (MKSAP) 16, 17 American College of Physicians, Philadelphia 2012, 2015
  4. Peeters M, Douillard JY, Van Cutsem E et al Mutant KRAS codon 12 and 13 alleles in patients with metastatic colorectal cancer: assessment as prognostic and predictive biomarkers of response to panitumumab. J Clin Oncol. 2013 Feb 20;31(6):759-65 PMID: 23182985