NEW YORK (Reuters Health) - Adding cetuximab to standard chemotherapy for colorectal liver metastases often shrinks inoperable lesions enough to permit resection, according to a study released today in the Online First issue of the Lancet Oncology.
With the addition of cetuximab, "one-third of the patients (34%) were actually completely resected for their metastatic disease, providing a chance of long term survival or even cure from the metastatic disease," Dr. Gunnar Folprecht, from University Hospital Carl Gustav Carus, Dresden, Germany, wrote in an email to Reuters Health.
Dr. Folprecht and his colleagues note in their report that while resection of colorectal liver metastases is potentially curative, most patients have non-resectable disease and a poor prognosis at presentation.
In their 17-center randomized trial, the investigators examined the effects of adding cetuximab to standard neoadjuvant FOLFOX6 (oxaliplatin, fluorouracil, and folinic acid) or FOLFIRI (irinotecan, fluorouracil, and folinic acid) chemotherapy in 109 patients with colorectal liver metastases that were inoperable either for technical reasons or because there were more than five lesions.
High tumor response rates were achieved with cetuximab and either FOLFOX6 or FOLFIRI, according to the article. Partial or complete tumor response was seen in 68% of patients in the cetuximab/FOLFOX6 arm and 57% in the cetuximab/FOLFIRI arm -- a nonsignificant difference of 11%.
As expected, tumor response rates were higher in patients with KRAS wild-type tumors (70%) compared with patients with KRAS tumor mutations (41%), a finding that supports prior studies showing that KRAS mutations confer resistance to cetuximab. "As previously known, the determination of mutations in the k-ras gene can select patients who do…or do not benefit from treatment with cetuximab," Dr. Folprecht said.
Importantly, the investigators point out, adding cetuximab increased the proportion of resectable cases from 32% at baseline to 60% with treatment.
Cetuximab plus FOLFOX6 or FOLFIRI was generally well tolerated. Mirroring prior studies, the most common grade 3/4 adverse events in the current study were skin reactions in 37 of 109 patients (34%) and neutropenia in 25 of 109 patients (23%).
Summing up, Dr. Folprecht said, "We think that this - to our knowledge - first randomized multicenter trial for treatment of non-resectable liver metastases has given important insights in the multidisciplinary treatment of these patients and that it has shown that cetuximab containing combinations are very effective therapy in this treatment situation."
This study and several of its authors were funded by Merck Serono, Sanofi-Aventis, and Pfizer.
Reference:
Lancet Oncol 2009.
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