title: A phase I/II study of weekly high-dose erlotinib in previously treated patients with nonsmall cell lung cancer.
abstract: BACKGROUND
  Preclinical studies have suggested that erlotinib at high doses may inhibit additional sites downstream of the epidermal growth factor receptor (EGFR), resulting in greater antitumor efficacy. The objective of this study was to determine the tolerability and efficacy of high-dose erlotinib administered on a weekly schedule to patients with advanced nonsmall cell lung cancer (NSCLC).
  
  
  METHODS
  The authors conducted a Phase I/II trial of weekly erlotinib in patients with progressive NSCLC who had received previous chemotherapy. In the Phase I portion, patients were enrolled in 3-patient cohorts at erlotinib dose levels of 1200 mg, 1600 mg, and 2000 mg once weekly. The Phase II portion was designed to determine the major objective response rate of the dose identified in the Phase I portion of the trial.
  
  
  RESULTS
  Twenty-seven patients were enrolled. No dose-limiting toxicity was observed. Grade 1 and 2 rash and diarrhea were the principle toxicities, and each occurred in 92% of patients. Among 21 patients who were treated at the Phase II dose of 2000 mg weekly, a single objective response was identified, yielding a response rate of 5% (95% confidence interval, 0.2-22%). For this cohort, the median survival was 9.5 months. The sole radiographic response occurred in a patient whose pretreatment tumor specimen harbored an EGFR exon 19 deletion.
  
  
  CONCLUSIONS
  Erlotinib at a dose of 2000 mg administered weekly was tolerated well by these patients with advanced NSCLC. The 5% objective response rate did not reach the stated objective at the interim efficacy analysis, prompting the closure of the study.
authors.affiliation: Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center and the Weill Medical College of Cornell University, New York, New York 10021, USA.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Milton
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Azzoli
authors.forename: Robert T
authors.initials: RT
authors.lastname: Heelan
authors.forename: Ennapadam
authors.initials: E
authors.lastname: Venkatraman
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Gomez
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
authors.forename: Lee M
authors.initials: LM
authors.lastname: Krug
authors.forename: William
authors.initials: W
authors.lastname: Pao
authors.forename: Naiyer A
authors.initials: NA
authors.lastname: Rizvi
authors.forename: Megan
authors.initials: M
authors.lastname: Dunne
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors