title: A phase II trial of ZD1839 (Iressa) 750 mg per day, an oral epidermal growth factor receptor-tyrosine kinase inhibitor, in patients with metastatic colorectal cancer.
abstract: OBJECTIVE
  The epidermal growth factor receptor (EGFR) appears relevant in the pathogenesis and progression of colorectal cancer. After completing a phase I pharmacodynamic trial of ZD1839, we undertook a dose expansion trial to examine the antitumour efficacy and adverse effect profile of this agent in a homogeneous group of patients with metastatic colorectal cancer (CRC).
  
  
  METHODS
  Eligible patients with metastatic or recurrent CRC received ZD1839 750 mg daily by mouth. This dose was selected based on a phase I trial conducted by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG). Treatment was continued until unacceptable toxicity or disease progression.
  
  
  RESULTS
  Twenty-eight patients were enrolled at three NCIC CTG centers. Twenty-three patients had received prior chemotherapy; 12 patients had received three or more regimens. No objective responses were observed in 24 evaluable patients, although 8 patients had stable disease (median duration of 2.2 months). The most frequent drug related adverse events were diarrhea, rash and nausea. Eleven patients required dosing modification (hold or reduction), while 3 patients discontinued therapy because of toxicity. There were no treatment related deaths.
  
  
  CONCLUSIONS
  ZD1839, when given at 750 mg/day to patients with pre-treated metastatic colorectal cancer, does not result in significant tumor regression.
authors.affiliation: Hamilton Regional Cancer Centre, 699 Concession St., Hamilton, ON, Canada L8V 5C2.
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Mackenzie
authors.forename: Holger W
authors.initials: HW
authors.lastname: Hirte
authors.forename: Goss
authors.initials: G
authors.lastname: Glenwood
authors.forename: Maroun
authors.initials: M
authors.lastname: Jean
authors.forename: Rakesh
authors.initials: R
authors.lastname: Goel
authors.forename: Pierre P
authors.initials: PP
authors.lastname: Major
authors.forename: Wilson H
authors.initials: WH
authors.lastname: Miller
authors.forename: Lawrence
authors.initials: L
authors.lastname: Panasci
authors.forename: Ian A J
authors.initials: IA
authors.lastname: Lorimer
authors.forename: Gerald
authors.initials: G
authors.lastname: Batist
authors.forename: Sarah
authors.initials: S
authors.lastname: Matthews
authors.forename: Lynn
authors.initials: L
authors.lastname: Douglas
authors.forename: Lesley
authors.initials: L
authors.lastname: Seymour
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D066246:ErbB Receptors / Q000187:drug effects*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib
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