The Pharmaceutical Journal
Vol 277 No 7423 p474
21 October 2006

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Data support scaling cetuximab dose to provoke rash

Scaling up the dose of the epidermal growth factor receptor (EGFR)-targeting agent cetuximab (Erbitux) for patients with metastatic colorectal cancer who do not initially develop a rash or develop only a grade 1 acneiform rash gives them a better chance of benefiting from the treatment. This is according to interim results of the study, known as EVEREST, presented at the European Society for Medical Oncology congress in Istanbul earlier this month.

Emergence of grade 3/4 rash with EGFR inhibitor and chemotherapy treatment has proved strongly prognostic for tumour response and survival. A robust response may also allow some patients to undergo liver metastases resection with a potential subsequent increase in five- and 10-year-survival.

EVEREST included 166 patients but randomised 89 who did not achieve marked rash within 21 days of receiving standard-dose cetuximab (loading dose 400mg/m² followed by 250mg/m² per week) to either a scaled-up dose or to remain on standard dosing.

Results showed doubling the dose by fortnightly 50mg increments to 500mg/m²/
week in patients with initial skin reaction of less than grade 2, provoked a more severe rash (grade 2 or more) and increased the response rate to 30 per cent compared with 13 per cent for those continuing on standard dosing. Non-randomised patients showing marked skin reactions from the start had a response rate of 34 per cent.

Presenting the results, Eric Van Cutsem, of Leuven University, Belgium, said: “This is proof of the concept that escalating the cetuximab dose in patients not developing rash initially can increase their chance of getting a response to the same extent as people developing pronounced rash from the start.” Biopsies taken during the study may help pinpoint the exact mechanism linking severity of rash and tumour response, he added.