Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor Journal Article


Authors: Saltz, L. B.; Meropol, N. J.; Loehrer, P. J. Sr; Needle, M. N.; Kopit, J.; Mayer, R. J.
Article Title: Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor
Abstract: Purpose: To evaluate the antitumor activity and toxicity of single-agent cetuximab in patients with chemotherapy-refractory colorectal cancer whose tumors express the epidermal growth factor receptor. Patients and Methods: Phase II, open-label clinical trial. Patients were required to have EGFr expression demonstrated on formalin-fixed paraffin-embedded tumor tissue by immunohistochemical staining before study participation. Patients were required to have received irinotecan, either alone or in a combination regimen, and to have demonstrated clinical failure on this regimen before study entry. Cetuximab was administered weekly by intravenous infusion. The first dose of 400 mg/m2 was given during the course of 2 hours. Subsequent weekly treatments were given at a dose of 250 mg/m2 during the course of 1 hour. Results: Fifty-seven eligible patients were treated. All were assessable for toxicity and response. The most commonly encountered grade 3 to 4 adverse events, regardless of relationship to study drug, were an acne-like skin rash, predominantly on the face and upper torso (86% with any grade; 18% with grade 3), and a composite of asthenia, fatigue, malaise, or lethargy (56% with any grade, 9% with grade 3). Two patients (3.5%) experienced grade 3 allergic reactions requiring discontinuation of study treatment. A third patient experienced a grade 3 allergic reaction that resolved, and the patient continued on the study. Neither diarrhea nor neutropenia were dose limiting in any of the 57 patients treated. Five patients (9%; 95% CI, 3% to 19%) achieved a partial response. Twenty-one additional patients had stable disease or minor responses. The median survival in these previously treated patients with chemotherapy-refractory colorectal cancer is 6.4 months. Conclusion: Cetuximab on this once-weekly schedule has modest activity and is well-tolerated as a single agent in patients with chemotherapy-refractory colorectal cancer whose tumors express the epidermal growth factor receptor. Further studies of cetuximab will evaluate the use of cetuximab in conjunction with first-line and adjuvant treatments for this disease. © 2004 by American Society of Clinical Oncology.
Keywords: immunohistochemistry; adult; human tissue; protein expression; treatment outcome; aged; aged, 80 and over; middle aged; survival rate; major clinical study; clinical trial; drug activity; drug tolerability; fatigue; neutropenia; diarrhea; dose response; antineoplastic agents; antineoplastic agent; colorectal cancer; metabolism; phase 2 clinical trial; epidermal growth factor receptor; receptor, epidermal growth factor; antineoplastic activity; cetuximab; irinotecan; monoclonal antibody; asthenia; rash; colorectal neoplasms; malaise; antibodies, monoclonal; immunotherapy; multicenter study; colorectal tumor; open study; lethargy; infusions, intravenous; allergic reaction; intravenous drug administration; humans; human; male; female; priority journal; article
Journal Title: Journal of Clinical Oncology
Volume: 22
Issue: 7
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2004-04-01
Start Page: 1201
End Page: 1208
Language: English
DOI: 10.1200/jco.2004.10.182
PROVIDER: scopus
PUBMED: 14993230
DOI/URL:
Notes: J. Clin. Oncol. -- Cited By (since 1996):1286 -- Export Date: 16 June 2014 -- CODEN: JCOND -- Source: Scopus
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  1. Leonard B Saltz
    735 Saltz