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


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/m(2) was given during the course of 2 hours. Subsequent weekly treatments were given at a dose of 250 mg/m(2) 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.


CONCLUSIONS
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.
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. Saltzl@mskcc.org
Leonard B
LB
Saltz
Neal J
NJ
Meropol
Patrick J
PJ
Loehrer
Michael N
MN
Needle
Justin
J
Kopit
Robert J
RJ
Mayer
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000628:therapy*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D000068818:Cetuximab