title: A phase II trial of erlotinib monotherapy for pretreated elderly patients with advanced EGFR wild-type non-small cell lung cancer.
abstract: BACKGROUND
  Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, which is an effective treatment for patients with non-small cell lung cancer (NSCLC), especially those harboring activating EGFR mutations. A previous phase III trial suggested that patients with EGFR wild-type (EGFR-wt) NSCLC or elderly patients with disease progression after cytotoxic chemotherapy might benefit from erlotinib monotherapy. However, few studies have prospectively evaluated the efficacy and safety of second- or third-line erlotinib monotherapy for elderly patients with EGFR-wt advanced or recurrent NSCLC.
  
  
  METHODS
  Pretreated patients aged ≥70 years with EGFR-wt stage IIIB/IV NSCLC or those with postoperative recurrence were enrolled and received oral erlotinib at a dose of 150 mg/day until disease progression. Primary outcome was the objective response rate (ORR). Secondary end points included the disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and toxicity profile.
  
  
  RESULTS
  This study was terminated early because of the results from a Japanese phase III trial (DELTA trial). Sixteen patients were enrolled between April 2010 and May 2013. The median age was 78 years (range 70-84 years). Six patients were female. Five patients had an Eastern Cooperative Oncology Group performance status of 0. Eleven (69%) patients had adenocarcinoma. Fifteen (94%) patients were treated with erlotinib as a second-line therapy. The ORR was 0% [95% confidence interval (CI) 0-17.1]. DCR was 56.3% (95% CI 33.2-76.9). The median PFS and OS were 1.7 months (95% CI 1.3-2.2) and 7.2 months (95% CI 5.6-8.7), respectively. The most commonly occurring adverse events included acneiform eruption (31.3%) and skin rash (25.0%). One patient developed grade 3 interstitial lung disease, which improved following steroid therapy.
  
  
  CONCLUSIONS
  In pretreated elderly patients with advanced or recurrent EGFR-wt NSCLC, daily oral erlotinib was well tolerated; however, administration of the drug should not be considered as a second line therapy.
  
  
  BACKGROUND
  University Hospital Medical Information Network (UMIN) Clinical Trials Registry UMIN000004561 (Date of registration: November 15th, 2010).
authors.affiliation: Department of Pulmonary Medicine, Fukushima Medical University, 1 Hikariga-oka, Fukushima, 960-1295, Japan. hiromine@fmu.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Minemura
authors.affiliation: Department of Pulmonary Medicine, Fukushima Medical University, 1 Hikariga-oka, Fukushima, 960-1295, Japan. yokouchi@fmu.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yokouchi
authors.affiliation: Department of Pulmonary Medicine, Fukushima Medical University, 1 Hikariga-oka, Fukushima, 960-1295, Japan. k-azuma@fmu.ac.jp.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Azuma
authors.affiliation: Department of Pulmonary Medicine, Fukushima Medical University, 1 Hikariga-oka, Fukushima, 960-1295, Japan. hirai-k@fmu.ac.jp.
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Hirai
authors.affiliation: Department of Pulmonary Medicine, Fukushima Medical University, 1 Hikariga-oka, Fukushima, 960-1295, Japan. sekine78ss@gmail.com.
authors.forename: Satoko
authors.initials: S
authors.lastname: Sekine
authors.affiliation: Department of Pulmonary Medicine, Fukushima Medical University, 1 Hikariga-oka, Fukushima, 960-1295, Japan. tohokunoichiro@yahoo.co.jp.
authors.forename: Kengo
authors.initials: K
authors.lastname: Oshima
authors.affiliation: Department of Pulmonary Medicine, Fukushima Medical University, 1 Hikariga-oka, Fukushima, 960-1295, Japan. k-kenya@fmu.ac.jp.
authors.forename: Kenya
authors.initials: K
authors.lastname: Kanazawa
authors.affiliation: Department of Pulmonary Medicine, Fukushima Medical University, 1 Hikariga-oka, Fukushima, 960-1295, Japan. ytanino@fmu.ac.jp.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tanino
authors.affiliation: Department of Pulmonary Medicine, Saiseikai Fukushima General Hospital, 25 Omori Aza Shimo-harada, Fukushima, 960-1101, Japan. inokoshi@fmu.ac.jp.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Inokoshi
authors.affiliation: Department of Pulmonary Medicine, Saiseikai Fukushima General Hospital, 25 Omori Aza Shimo-harada, Fukushima, 960-1101, Japan. tae-i@fmu.ac.jp.
authors.forename: Taeko
authors.initials: T
authors.lastname: Ishii
authors.affiliation: Department of Pulmonary Medicine, Saiseikai Fukushima General Hospital, 25 Omori Aza Shimo-harada, Fukushima, 960-1101, Japan. yutaka.yocchan@gmail.com.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Katsuura
authors.affiliation: Department of Thoracic Surgery, Fukushima Red Cross Hospital, 11-31 Irie-cho, Fukushima, 960-8530, Japan. ikyoku31@fukushima-med-jrc.jp.
authors.forename: Akio
authors.initials: A
authors.lastname: Oishi
authors.affiliation: Department of Pulmonary Medicine, Fukushima Medical University, 1 Hikariga-oka, Fukushima, 960-1295, Japan. taku.ishida@nifty.ne.jp.|Clinical Oncology Center, Fukushima Medical University Hospital, 1 Hikariga-oka, Fukushima, 960-1295, Japan. taku.ishida@nifty.ne.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishida
authors.affiliation: Department of Pulmonary Medicine, Fukushima Medical University, 1 Hikariga-oka, Fukushima, 960-1295, Japan. munakata@fmu.ac.jp.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Munakata
mesh_terms: D000284:Administration, Oral; D000367:Age Factors; 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* / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D057239:Early Termination of Clinical Trials; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors