Panitumumab.
Panitumumab, previously known as ABX-EGF, is the first fully human monoclonal antibody to be shown to be effective as a treatment for solid-tumor cancers. Its target is the epidermal growth factor receptor (EGFR), which when overactive may contribute to the development and progression of cancer and is expressed in several solid tumors, including colorectal cancer. In a recently reported phase III trial, patients with metastatic colorectal cancer who had failed previous treatment with oxaliplatin- and irinotecan-based therapy were randomized to receive single-agent panitumumab and best-supportive care, or best-supportive care alone. This trial demonstrated a significant improvement in progression-free survival with panitumumab treatment in these patients. A rash similar to that which occurs with the other anti-EGFR antibody, cetuximab, has been observed in up to 100% of patients treated with panitumumab in the various clinical trials. As with other EGFR antagonists, EGFR staining by immunohistochemistry has not been shown to be an effective method of selecting patients for treatment, whereas the severity of the rash appears to be predictive of outcome. Ongoing randomized trials are evaluating the use of panitumumab with combination treatment for the first-line treatment of metastatic colorectal cancer. This review summarizes the rationale for targeting the EGFR and the development of panitumumab in preclinical and early phase trials in several tumor types. Clinical trial results in colorectal cancer, in which the development of this agent is most advanced, will also be discussed, as will the rash associated with treatment.
Chua
Yu Jo
YJ
Department of Medicine, Royal Marsden Hospital, London and Surrey, UK. yujo.chua@rmh.nhs.uk
Cunningham
David
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D066246:ErbB Receptors / Q000276:immunology*; D005076:Exanthema / Q000209:etiology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D000077544:Panitumumab
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000077544:Panitumumab; D066246:ErbB Receptors