What’s the Best Treatment for Metastatic Colorectal Cancer?
April 7, 2011 Leave a comment
The answer is: nobody knows.
We have previously described a patient with a small bowel cancer for whom a treatment regimen contrary to the most widely used triplet was recommended. While it is arguable that small bowel adenocarcinoma is rare enough that no one really has a favorite regimen, colorectal management has become somewhat rigidly focused on FOLFOX. Yet, this popular combination may not be right for every patient with colon cancer.
We know, for example, that FOLFOX combined with Avastin provided no advantage in the adjuvant setting. We also know that the random addition of Erbitux to FOLFOX similarly failed to provide an advantage. As the modes of action differ between drugs, it is not surprising that subsets of colon cancer patients may do better with Irinotecan based therapies. Indeed, clinical trials combining the new monoclonal antibodies with Irinotecan have proven quite favorable, including the 2007 BOND-2 trial reported by investigators at Memorial Sloan Kettering in New York.
With this in mind, patients who present with both untreated colon cancer and a favorable profile for Irinotecan based combinations always interest us. One such patient presented to our attention in the last few weeks. This patient, in his mid 30s, was found to have inoperable, widely metastatic disease with extensive liver involvement. Confirmatory biopsies provided tissue for analysis and revealed no evidence of mismatch repair.
The results of the EVA-PCD platform were interesting on many levels. First, the EGFr active drugs provided a uniquely favorable profile, as did the down-stream inhibition of the MEK-ERK inhibitor we studied. These findings strongly suggested that the patient was RAS wild type (i.e. non-mutated). It is known that RAS mutation confers resistance to the EGFr active drugs. By inference, his sensitivity to the EGFr active drugs was prima facie evidence of RAS wild type, a finding that was confirmed later by molecular analysis. There was also a favorable profile for VEGF active drugs. Most favorable of all was the combination of Irinotecan with inhibitors of both VEGF and EGFr. This was the regimen that we selected.
We wait with interest the results of the therapy, as re-staging for response will be conducted in the coming months.