title: Optimizing response to gefitinib in the treatment of non-small-cell lung cancer.
abstract: The epidermal growth factor receptor (EGFR) is expressed in the majority of non-small-cell lung cancer (NSCLC). However, only a restricted subgroup of NSCLC patients respond to treatment with the EGFR tyrosine kinase inhibitor (EGFR TKI) gefitinib. Clinical trials have demonstrated that patients carrying activating mutations of the EGFR significantly benefit from treatment with gefitinib. In particular, mutations of the EGFR TK domain have been shown to increase the sensitivity of the EGFR to exogenous growth factors and, at the same time, to EGFR TKIs such as gefitinib. EGFR mutations are more frequent in patients with particular clinical and pathological features such as female sex, nonsmoker status, adenocarcinoma histology, and East Asian ethnicity. A close correlation was found between EGFR mutations and response to gefitinib in NSCLC patients. More importantly, randomized Phase III studies have shown the superiority of gefitinib compared with chemotherapy in EGFR mutant patients in the first-line setting. In addition, gefitinib showed a good toxicity profile with an incidence of adverse events that was significantly lower compared with chemotherapy. Therefore, gefitinib is a major breakthrough for the management of EGFR mutant NSCLC patients and represents the first step toward personalized treatment of NSCLC.
authors.affiliation: Pharmacogenomic Laboratory, CROM - Centro Ricerche Oncologiche di Mercogliano, Avellino, Italy;
authors.forename: Pietro
authors.initials: P
authors.lastname: Carotenuto
authors.forename: Cristin
authors.initials: C
authors.lastname: Roma
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Rachiglio
authors.forename: Raffaella
authors.initials: R
authors.lastname: Pasquale
authors.forename: Renato
authors.initials: R
authors.lastname: Franco
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Antinolfi
authors.forename: Francovito
authors.initials: F
authors.lastname: Piantedosi
authors.forename: Alfonso
authors.initials: A
authors.lastname: Illiano
authors.forename: Gerardo
authors.initials: G
authors.lastname: Botti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Morabito
authors.forename: Nicola
authors.initials: N
authors.lastname: Normanno
authors.forename: Antonella
authors.initials: A
authors.lastname: De Luca