title: A prospective, multicentre phase II trial of low-dose erlotinib in non-small cell lung cancer patients with EGFR mutations pretreated with chemotherapy: Thoracic Oncology Research Group 0911.
abstract: BACKGROUND
  Low-dose erlotinib may be as effective as gefitinib or erlotinib at full dose in non-small cell lung cancer (NSCLC) patients with activating mutations of the epidermal growth factor receptor (EGFR) gene.
  
  
  METHODS
  Patients with chemotherapy pretreated NSCLC harbouring EGFR mutations received erlotinib at 50 mg/d until disease progression or unacceptable toxicities. The dose was escalated to 150 mg/d in patients showing no response (i.e. without major tumour shrinkage according to Response Evaluation Criteria in Solid Tumours (RECIST)) to the initial dose during the first 4 weeks. The primary end-point was the objective response rate at the dose of 50 mg/d.
  
  
  RESULTS
  Thirty-four patients from seven institutes were enrolled. The study was closed early when no response was confirmed in 15 patients, excluding the possibility that the primary end-point would be met. The objective response and disease control rates at the dose of 50 mg/d as determined by an independent review committee were 54.5% and 84.8%, respectively. Four additional patients achieved partial response with increased 150 mg/d dose. Progression-free survival and median survival times during the entire period of the study were 9.5 and 28.5 months, respectively. Treatment-related toxicities were generally mild, the most common being skin disorders and diarrhoea. Only one case experienced grade 3 toxicity, which was transient increase of hepatic enzymes.
  
  
  CONCLUSIONS
  The primary end-point was not met; low-dose erlotinib is not recommended for fit patients with NSCLC harbouring EGFR mutations. However, it may merit further evaluation for elderly or frail patients.
authors.affiliation: Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan. Electronic address: kayamada@med.kurume-u.ac.jp.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Respiratory Medicine, Mitsui Memorial Hospital, Tokyo, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Aono
authors.affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hosomi
authors.affiliation: Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, Kanagawa, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okamoto
authors.affiliation: Division of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Kanagawa, Japan.
authors.forename: Terufumi
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Respiratory Internal Medicine, St. Marianna University School of Medicine, Yokohama-City Seibu Hospital, Kanagawa, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Komase
authors.affiliation: Department of Respiratory Medicine, Fujisawa City Hospital, Kanagawa, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nishikawa
authors.affiliation: Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Azuma
authors.affiliation: Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takeoka
authors.affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Okuma
authors.affiliation: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan; Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Nakahara
authors.affiliation: Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, Kanagawa, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Sato
authors.affiliation: Department of Biostatistics, Yokohama City University Medical Center, Kanagawa, Japan.
authors.forename: Mari S
authors.initials: MS
authors.lastname: Oba
authors.affiliation: Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.affiliation: Respiratory Medicine, Mitsui Memorial Hospital, Tokyo, Japan; Department of Medical Oncology, Japanese Red Cross Medical Center, Tokyo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Kunitoh
authors.affiliation: Thoracic Oncology Research Group, Kanagawa, Japan.
authors.forename: Koshiro
authors.initials: K
authors.lastname: Watanabe
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* / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D057239:Early Termination of Clinical Trials; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR mutation; Erlotinib; Low-dose; Non-small cell lung cancer