Panitumumab (Approved investigational) DB01269 Use : For the treatment of EGFR-expressing, metastatic colorectal carcinoma that is refractory to fluoropyrimidine-, oxaliplatin-, and irinotecan- containing chemotherapy regimens in humans and other mammals. Descriptions : Panitumumab (ABX-EGF) is a recombinant human IgG2 monoclonal antibody that binds specifically to the human epidermal growth factor receptor (EGFR). This drug is an antineoplastic agent. Targets : Epidermal growth factor receptor Half life : 7.5 days (range: 4-11 days)

Mechanism of action : Panitumumab binds specifically to EGFR on both normal and tumor cells, and competitively inhibits the binding of ligands for EGFR. Nonclinical studies show that binding of panitumumab to the EGFR prevents ligand-induced receptor autophosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, decreased pro-inflammatory cytokine and vascular growth factor production, and internalization of the EGFR.

Toxicity : Panitumumab was shown to cause skin, ocular and mucosal related toxicities in 90% of patients receiving panitumumab. Subsequent to the development of severe dermatologic toxicities, infectious complications, including sepsis, septic death, and abscesses requiring incisions and drainage, were reported. Clearance : 4.9+/- 1.4 mL/kg/day [Following single-dose administrations of panitumumab as 1-hour infusions] Brand : Amgen’s Vectibix Injection for intravenous infusion

Indications and usage : Vectibix is an epidermal growth factor receptor (EGFR) antagonist indicated for the treatment of wild-type KRAS (exon 2) metastatic colorectal cancer (mCRC) as determined by an FDA-approved test for this use: In combination with FOLFOX for first-line treatment. As monotherapy following disease progression after prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan-containing chemotherapy. Limitation of Use : Vectibix is not indicated for the treatment of patients with KRAS-mutant mCRC or for whom KRAS mutation status is unknown. Vectibix in combination with oxaliplatin-based chemotherapy is not indicated for the treatment of patients with RAS- mutant mCRC or for whom RAS mutation status is unknown.

Dosage and administration : Administer 6 mg/kg every 14 days as an intravenous infusion over 60 minutes (≤ 1000 mg) or 90 minutes (> 1000 mg). Infusion Reactions: Reduce infusion rate by 50% for mild reactions; terminate the infusion for severe infusion reactions.Dermatologic Toxicity : Withhold or discontinue for severe or intolerable toxicity; reduce dose for recurrent, grade 3 toxicity. Forms and strength : Single-use vials (20 mg/mL): 100 mg/5 mL, 200 mg/10 mL, 400 mg/20 mL

General reference : Foon KA, Yang XD, Weiner LM, Belldegrun AS, Figlin RA, Crawford J, Rowinsky EK, Dutcher JP, Vogelzang NJ, Gollub J, Thompson JA, Schwartz G, Bukowski RM, Roskos LK, Schwab GM: Preclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody. Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):984-90. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/14967460# Yang XD, Jia XC, Corvalan JR, Wang P, Davis CG: Development of ABX- EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy. Crit Rev Oncol Hematol. 2001 Apr;38(1):17-23. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/11255078# Wu M, Rivkin A, Pham T: Panitumumab: human monoclonal antibody against epidermal growth factor receptors for the treatment of metastatic colorectal cancer. Clin Ther. 2008 Jan;30(1):14-30. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/18343240# Saadeh CE, Lee HS: Panitumumab: a fully human monoclonal antibody with activity in metastatic colorectal cancer. Ann Pharmacother. 2007 Apr;41(4):606-13. Epub 2007 Mar 13. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/17355997# Keating GM: Panitumumab: a review of its use in metastatic colorectal cancer. Drugs. 2010 May 28;70(8):1059-78. doi: 10.2165/11205090-000000000-00000. "Pubmed":http://www.ncbi.nlm.nih.gov/pubmed/20481659