title: Erlotinib in patients with advanced non-small-cell lung cancer: impact of dose reductions and a novel surrogate marker.
abstract: Erlotinib is a relatively well-tolerated treatment option for patients with advanced non-small-cell lung cancer (NSCLC). Some patients suffer from severe skin toxicity or diarrhea, making dose reductions or even treatment cessation necessary. Recent clinical trials usually defined a 100 mg daily dose as the lowest acceptable dose, whereas little is known about the efficacy with lower doses. We retrospectively reviewed the files of all patients with advanced non-small-cell lung cancer (NSCLC) treated with erlotinib. We assessed demographic, disease- and treatment-related information. We tried to correlate tolerability with clinical efficacy. EGF receptor exon 18/19/21 mutations were analyzed in selected patients. Fifty-three patients with advanced non-small-cell lung cancer were treated with erlotinib. In nine patients (17%), the doses had to be reduced to 75 or 50 mg daily due to toxicity. We observed several sustained disease stabilizations in this subgroup. Patients suffering from paronychia with erlotinib had a significantly longer time to progression than did subjects without nail toxicity (P = 0.04). If patients were free from any toxicity, they were at high risk for early tumor progression (P = 0.001) and death. In patients with disease stabilization for 6 months or longer, we observed EGFR 18/19/21 wild type, exon 19 and exon 21 mutations. In conclusion, several patients required dose reductions during treatment with erlotinib. However, in tumors with sensitivity to erlotinib, even daily doses of 50-75 mg can result in sustained disease control. Paronychia represents a favorable surrogate marker for efficacy.
authors.affiliation: Department of Internal Medicine/Infectious and Respiratory Diseases, Charité-Universitätsmedizin Berlin, Berlin, Germany. daniel.binder@charite.de
authors.forename: Daniel
authors.initials: D
authors.lastname: Binder
authors.forename: Ann-Christin
authors.initials: AC
authors.lastname: Buckendahl
authors.forename: Ralf-Harto
authors.initials: RH
authors.lastname: Hübner
authors.forename: Peter
authors.initials: P
authors.lastname: Schlattmann
authors.forename: Bettina
authors.initials: B
authors.lastname: Temmesfeld-Wollbrück
authors.forename: Thomas
authors.initials: T
authors.lastname: Beinert
authors.forename: Norbert
authors.initials: N
authors.lastname: Suttorp
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015415:Biomarkers / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D000069347:Erlotinib Hydrochloride; D005260:Female; D018773:Genes, erbB-1; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010304:Paronychia / Q000139:chemically induced*; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride