Cetuximab in non-small-cell lung cancer.
Cetuximab is a chimeric human-mouse anti-EGF receptor monoclonal antibody. In Phase I studies, no dose-limiting toxicities were observed with cetuximab as a single agent or combined with chemotherapy; pharmacokinetic and pharmacodynamic analyses supported 250 mg/m(2) weekly administration. Skin toxicity, diarrhea and fatigue were the most common toxicities. The positive results obtained in Phase II trials in patients with advanced non-small-cell lung cancer prompted two randomized Phase III trials evaluating cetuximab in addition to first-line chemotherapy. Both trials showed a small benefit in overall survival for the experimental treatment, which was considered insufficient by the EMA for marketing approval. However, a subgroup analysis of the FLEX Phase III trial recently demonstrated a larger survival benefit from the experimental treatment in patients with high immunohistochemical EGF receptor expression. This finding, if confirmed prospectively, could represent a new opportunity for positioning cetuximab into the standard treatment of advanced non-small-cell lung carcinoma.
Medical Oncology Unit, Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro, Italy.
Guido
G
Carillio
Agnese
A
Montanino
Raffaele
R
Costanzo
Claudia
C
Sandomenico
Maria Carmela
MC
Piccirillo
Massimo
M
Di Maio
Gennaro
G
Daniele
Pasqualina
P
Giordano
Jane
J
Bryce
Nicola
N
Normanno
Gaetano
G
Rocco
Francesco
F
Perrone
Alessandro
A
Morabito
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D000068818:Cetuximab; D002986:Clinical Trials as Topic / Q000379:methods; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D000068818:Cetuximab