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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

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Summary

Purpose: 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). Experimental design: 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.

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Authors and Affiliations

  1. Hamilton Regional Cancer Centre, 699 Concession St., Hamilton, ON, Canada, L8V 5C2

    Mary J. MacKenzie, Holger W. Hirte & Pierre P. Major

  2. Ottawa Regional Cancer Centre, 503 Smyth Rd., Ottawa, ON, Canada, K1H 1C4

    Goss Glenwood, Maroun Jean, Rakesh Goel & Ian A. J. Lorimer

  3. Sir Mortimer B. Davis Jewish General Hospital, Montreal, PQ, Canada

    Wilson H. Miller Jr., Lawrence Panasci & Gerald Batist

  4. NCIC Clinical Trials Group, Kingston, ON, Canada

    Sarah Matthews & Lesley Seymour

  5. AstraZeneca Canada Mississauga, ON, Canada

    Lynn Douglas

  6. NCIC Clinical Trials Group, Kingston, Ontario, K7L 3N6, Canada

    Lesley Seymour

Authors
  1. Mary J. MacKenzie
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  2. Holger W. Hirte
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  3. Goss Glenwood
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  4. Maroun Jean
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  5. Rakesh Goel
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  6. Pierre P. Major
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  7. Wilson H. Miller Jr.
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  8. Lawrence Panasci
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  9. Ian A. J. Lorimer
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  10. Gerald Batist
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  11. Sarah Matthews
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  12. Lynn Douglas
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  13. Lesley Seymour
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Corresponding author

Correspondence to Lesley Seymour.

Additional information

This study was supported by the National Cancer Institute of Canada and AstraZeneca Canada

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MacKenzie, M.J., Hirte, H.W., Glenwood, G. et al. 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. Invest New Drugs 23, 165–170 (2005). https://doi.org/10.1007/s10637-005-5862-9

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  • DOI: https://doi.org/10.1007/s10637-005-5862-9

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