Use of the epidermal growth factor receptor inhibitors gefitinib and erlotinib in the treatment of non-small cell lung cancer: a systematic review.
BACKGROUND
Inhibition of the epidermal growth factor receptor is a promising therapy in the treatment of non-small cell lung cancer (NSCLC). In this systematic review, we evaluated the role of the epidermal growth factor receptor inhibitors gefitinib and erlotinib in the treatment of patients with advanced NSCLC.


METHODS
Relevant randomized trials published as articles or abstracts were identified through a systematic search of the literature from 1975 to November 2005 by two independent reviewers.


RESULTS
Twelve randomized trials met the predefined eligibility criteria for this systematic review. Four large placebo-controlled trials demonstrated that the addition of gefitinib or erlotinib to platinum-based first-line chemotherapy did not significantly improve overall survival or time-to-disease progression. A large placebo-controlled trial revealed a clinically and statistically significant survival benefit for erlotinib therapy as second- or third-line systemic therapy. The results of a single placebo-controlled trial and two phase II trials suggest that modest tumor response rates and symptom control can be achieved with gefitinib as second-line or subsequent therapy; however, a statistically significant survival benefit was not found for gefitinib compared with placebo.


CONCLUSIONS
There is strong evidence to recommend against the use of gefitinib or erlotinib in combination with chemotherapy or as maintenance therapy after chemotherapy and radiation as a first-line treatment for advanced NSCLC. Erlotinib monotherapy is an effective treatment that can prolong survival for patients with advanced NSCLC whose disease has relapsed or recurred after prior chemotherapy. Although a significant survival benefit has not been demonstrated for gefitinib in a placebo-controlled study, the two randomized phase II trials suggest that gefitinib may provide clinically important symptomatic benefits.
Feld
Ron
R
Princess Margaret Hospital, Toronto, Ontario, Canada.
Sridhar
Srikala S
SS
Shepherd
Frances A
FA
Mackay
Jean A
JA
Evans
William K
WK
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000523:psychology; D011788:Quality of Life; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib