title: Gefitinib in combination with irradiation with or without cisplatin in patients with inoperable stage III non-small cell lung cancer: a phase I trial.
abstract: OBJECTIVE
  To establish the feasibility and tolerability of gefitinib (ZD1839, Iressa) with radiation (RT) or concurrent chemoradiation (CRT) with cisplatin (CDDP) in patients with advanced non-small cell lung cancer (NSCLC).
  
  
  METHODS
  In this multicenter Phase I study, 5 patients with unresectable NSCLC received 250 mg gefitinib daily starting 1 week before RT at a dose of 63 Gy (Step 1). After a first safety analysis, 9 patients were treated daily with 250 mg gefitinib plus CRT in the form of RT and weekly CDDP 35 mg/m(2) (Step 2). Gefitinib was maintained for up to 2 years until disease progression or toxicity.
  
  
  RESULTS
  Fourteen patients were assessed in the two steps. In Step 1 (five patients were administered only gefitinib and RT), no lung toxicities were seen, and there was no dose-limiting toxicity (DLT). Adverse events were skin and subcutaneous tissue reactions, limited to Grade 1-2. In Step 2, two of nine patients (22.2%) had DLT. One patient suffered from dyspnea and dehydration associated with neutropenic pneumonia, and another showed elevated liver enzymes. In both steps combined, 5 of 14 patients (35.7%) experienced one or more treatment interruptions.
  
  
  CONCLUSIONS
  Gefitinib (250 mg daily) in combination with RT and CDDP in patients with Stage III NSCLC is feasible, but CDDP likely enhances toxicity. The impact of gefitinib on survival and disease control as a first-line treatment in combination with RT remains to be determined.
authors.affiliation: Radiation Oncology, Zurich University Hospital, University of Zurich, Zurich, Switzerland.
authors.forename: Sacha
authors.initials: S
authors.lastname: Rothschild
authors.forename: Stephan E
authors.initials: SE
authors.lastname: Bucher
authors.forename: Jacques
authors.initials: J
authors.lastname: Bernier
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Aebersold
authors.forename: Aberrahim
authors.initials: A
authors.lastname: Zouhair
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ries
authors.forename: Norbert
authors.initials: N
authors.lastname: Lombrieser
authors.forename: Thomas
authors.initials: T
authors.lastname: Lippuner
authors.forename: Urs M
authors.initials: UM
authors.lastname: Lütolf
authors.forename: Christoph
authors.initials: C
authors.lastname: Glanzmann
authors.forename: I Frank
authors.initials: IF
authors.lastname: Ciernik
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D016190:Carboplatin; D002945:Cisplatin; D000077156:Gefitinib