NEW YORK -- November 24, 2009 -- Adding cetuximab to neoadjuvant chemotherapy can shrink tumours leading to increased potentially curative surgery in patients who have colorectal cancer with inoperable metastatic liver lesions, according to a study published online first in The Lancet Oncology.
Gunnar Folprecht, University Hospital Carl Gustav Carus, Dresden, Germany, and colleagues from Germany and Austria conducted the randomised Cetuximab in Neoadjuvant Treatment of Non-Resectable Colorectal Liver Metastases (CELIM) trial.
CELIM examined the effectiveness of adding cetuximab to neoadjuvant chemotherapy to improve tumour response and maximise rates of potentially curable surgery in patients with colorectal liver metastases (CLM).
A total of 109 patients were randomly assigned to treatment with cetuximab plus oxaliplatin, fluorouracil, and folinic acid (FOLFOX6; group A) or cetuximab plus irinotecan, fluorouracil, and folinic acid (FOLFIRI; group B).
Tumour response and suitability for surgery were assessed every 4 cycles (8 weeks) using computed tomography (CT) or magnetic resonance imaging (MRI). Patients with resectable disease, after assessment, were offered liver surgery. The authors also did a blinded surgical review of MRI and CT scans to provide an objective assessment of how suitability for surgery changed during treatment.
Findings showed that treatment with cetuximab resulted in high tumour response rates and a significant increase (28%) in the proportion of tumours that were amenable to surgery compared with at the start of the study.
Partial or complete tumour response was shown in 68% of patients in group A and 57% of patients in group B. Tumour response was higher in patients with KRAS wild-type tumours (70%) compared with patients with KRAS tumour mutations (41%), consistent with results of previous studies which have shown that this mutation confers resistance to cetuximab.
Overall, surgery was achieved in 36 of 106 patients (34%). Importantly, the blinded review found that treatment with cetuximab significantly increased the proportion of tumours that were amenable to surgery, with 60% (41 of 68 patients) of tumours judged to be resectable after treatment compared with 32% (22 of 68 patients) at the start of the study.
The treatment was generally well tolerated. Grade 3 toxicity occurred in 72% of patients, the most common toxicities being skin reactions and neutropenia.
"Our data suggest that treatment with cetuximab and chemotherapy results in high confirmed tumour response rates...leading to…increased resectability…In the light of recent studies in metastatic colorectal cancer the value of further treatment intensification will be investigated."
SOURCE: The Lancet Oncology
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