Erlotinib: small-molecule targeted therapy in the treatment of non-small-cell lung cancer.
BACKGROUND
Erlotinib is an oral tyrosine kinase inhibitor, targeting the human epidermal receptor type 1/ epidermal growth factor receptor, recently approved by the US Food and Drug Administration (FDA) for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) after the failure of more than 1 or 2 previous chemotherapeutic regimens.


OBJECTIVE
The purpose of this article is to summarize the development, pharmacology, pharmacokinetics, efficacy, and adverse effects of erlotinib.


METHODS
A literature search was conducted with the MEDLINE and EMBASE (1999-2005) databases using the search terms non-small-cell lung cancer, erlotinib, and epidermal growth factor receptor inhibitor. Abstracts from the American Society of Clinical Oncology and documents submitted to the FDA also were reviewed.


RESULTS
BR.21, a randomized, placebo-controlled, multinational Phase III trial demonstrated clinically and statistically improved overall survival in patients with advanced or metastatic NSCLC treated with erlotinib versus placebo as second-line therapy. The erlotinib group had a median survival of 6.7 months versus a median survival of 4.7 months in the placebo group (P < 0.001). The toxicity profile of erlotinib was moderately benign, with the most commonly documented adverse events requiring dose reductions including skin rash (12%) and diarrhea (5%). Interstitial lung disease and relative fatalities were reported infrequently (0.8%) in patients receiving erlotinib. Two randomized, placebo-controlled, multicenter Phase III trials conducted in patients with locally advanced and metastatic NSCLC showed no clinical benefit with first-line administration of erlotinib plus concurrent platinum-based chemotherapy.


CONCLUSIONS
For patients with NSCLC in whom more than 1 or 2 previous chemotherapeutic regimens have failed, erlotinib is an effective therapy with significant overall survival benefits. The use of erlotinib as first-line therapy in combination with platinum-based chemotherapeutic regimens, however, has failed to demonstrate efficacy in the treatment of NSCLC.
Smith
Janine
J
Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, 08852, USA. janines_us@yahoo.com
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000191:economics / Q000473:pathology; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000191:economics / Q000473:pathology; D015394:Molecular Structure; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D011799:Quinazolines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D016019:Survival Analysis
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases