title: Gefitinib as a first-line therapy of advanced or metastatic adenocarcinoma of the lung in never-smokers.
abstract: OBJECTIVE
  A subset of patients with adenocarcinoma of the lung who had never smoked cigarettes showed excellent tumor responses to gefitinib therapy. To evaluate the efficacy of gefitinib as a first-line therapy in this subgroup of patients, we conducted a phase II study.
  
  
  METHODS
  Eligible patients had no smoking history, stage IIIB or IV adenocarcinoma, Eastern Cooperative Oncology Group performance status 0 to 2, and adequate organ functions. Treatment consisted of daily oral administration ofF 250 mg gefitinib for 28 days until disease progression. Responses were assessed after every two cycles of therapy.
  
  
  RESULTS
  Of 37 patients enrolled, 36 were assessed for response. Twenty-five patients (69%) had partial response, 4 (11%) had stable disease, and 7 (19%) had progressive disease. Of 10 patients with evaluable brain metastases, 7 had objective responses in both intracranial and extracranial lesions, 1 had stable disease in the brain and dramatic response in the extracranial lesions, and 2 had progressive disease in both sites. After a median follow-up of 48 weeks (range, 4-70 weeks), 26 patients had disease progression, with median progression-free survival of 33 weeks, and 9 patients died, all due to disease progression. The median survival time has not been reached yet but the estimated 1-year survival rate was 73%. Common toxicities were skin rash and mild diarrhea but there was no significant hematologic toxicity.
  
  
  CONCLUSIONS
  Gefitinib showed very dramatic antitumor activity, even in the brain, with unprecedented survival outcome in never-smoker adenocarcinoma patients. These data support the use of gefitinib as a first-line therapy in this particular subgroup.
authors.affiliation: Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, South Korea.
authors.forename: Dae Ho
authors.initials: DH
authors.lastname: Lee
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Han
authors.forename: Hong Gi
authors.initials: HG
authors.lastname: Lee
authors.forename: Jae Jin
authors.initials: JJ
authors.lastname: Lee
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Lee
authors.forename: Hyae Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Hark Kyun
authors.initials: HK
authors.lastname: Kim
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Hong
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000517:prevention & control / Q000556:secondary; D018450:Disease Progression; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D005500:Follow-Up Studies; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D012871:Skin Diseases / Q000139:chemically induced; D012907:Smoking; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D000077156:Gefitinib