Cetuximab (IMC-C225) plus Weekly Irinotecan (CPT-11), Fluorouracil (5FU), and Leucovorin (LV) in Colorectal Cancer (CRC) that Expresses the Epidermal Growth Factor Receptor (EGFR)

Reviewer: Mary Kara Bucci, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 19, 2002

Presenter: Arthur Rosenberg
Presenter's Affiliation: The Bendheim Cancer Center of Greenwich Hospital, Connecticut
Type of Session: Poster


    Previous studies have shown that increased expression of Epidermal Growth Factor Receptor (EGFR) conveys an unfavorable prognosis in multitude of cancers, including colorectal cancer. Cetuximab (IMC-C225) is a humanized monoclonal antibody that binds selectively to EGFR, thereby inhibiting the binding of the Epidermal Growth Factor to this receptor. A previous trial demonstrated a 22.5 % response rate to Cetuximab plus Irinotecan (CPT-11) in 120 patients with CPT-11 refractory, EGFR-positive colorectal cancer. This response appeared independent of EGFR over-expression. This current study builds upon those findings by combining Cetuximab with weekly CPT-11, 5FU, and LV, a standard regimen, for metastatic colorectal cancer with expression of EGFR.

Materials and Methods

  • 29 patients with measurable metastatic colorectal cancer and immunohistochemical evidence of EGFR expression were enrolled on this trial.
  • Patients were treated with a combination of weekly CPT-11, 5FU, and LV on the first 4 weeks of a six week cycle. Cetuximab was given weekly for all 6 weeks.
  • The initial dose of Cetuximab was 400 mg/m2 infused over 120 minutes. Subsequent doses were 250 mg/m2 and were infused over 60 min.
  • CPT-11, 125 mg/m2, was given 1 hour after the Cetuximab infusion. This was immediately followed by LV, 20 mg/m2, and 5FU, 500 mg/m2. All drugs were given intravenously.
  • After the first 6 patients were enrolled on this trial, new guidelines for the administration of CPT-11/5FU/LV were published (Saltz, N Eng J Med. 2000;343:905-14), outlining recommendations for dose reductions according to patient toxicity. Doses in this study were reduced according to these guidelines.


  • 7 patients reported serious adverse events that were considered to be related to Cetuximab, including thrombophlebitis (7%), gastroenteritis (3%), neutropenia (3%), dehydration (3%), pulmonary embolus (3%), and acute renal failure (3%).
  • Adverse events most frequently reported, regardless of relation to Cetuximab, were: acne (76%), nausea (69%), diarrhea (69%), mucositis (59%), neutropenia (59%), asthenia (55%), vomiting (45%), weight loss (35%), fever (35%) and anorexia (35%).
  • Grade 3-4 adverse events included diarrhea (28%), neutropenia (28%), acne (21%), asthenia (10%), and dehydration (10%).
  • One patient died from sepsis during the study.
  • 9 patients were discontinued from the study due to progressive disease, one patient was discontinued due to a serious adverse effect, and one was discontinued for an unknown reason. 17 patients are undergoing continuing treatement.
  • 14 of 29 patients (48%) have had a partial response
  • 12 patients have had stable disease (3 pts, 10%) or a minor response (9 pts, 31%), and 2 patients (7%) have progessed. One patient is not evaluable.

Author's Conclusions

  • The authors conclude that addition of Cetuximab to CPT-11/5FU/LV is safe and tolerable, with vigilant monitoring.
  • Most patients required a dose reduction of CPT-11.
  • The authors recommend further investigation of Cetuximab, with reduced doses of CPT-11 (100 mg/m2) and 5FU (400 mg/m2).

Clinical/Scientific Implications

    This study is one of several presented at this meeting demonstrating the relative safety and efficacy of Cetuximab in a variety of cancers with EGFR expression. The size of this study was limited and dose reductions were required, however the 48% response rate is encouraging. Further investigation is indicated.

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