For colorectal liver metastasis (CRLM), surgical resection is now established as the standard treatment option. The recent advance of anti-cancer drugs including the molecular-targeted agents enables us to extend the surgical indication and improve prognosis in a case with advanced CRLM. Because mFOLFOX with cetuximab has been expected to provide early tumor shrinkage for advanced-stage CRLM with KRAS wild type, we conducted this phase II trial to prospectively evaluate the significance of the treatment strategy.
Patients having advanced CRLM (tumor number > =5 and/or technically unresectbale) with KRAS wild were included to this study. First, mFOLFOX with cetuximab was induced, and surgical indication was evaluated every 4 cycles (2 months). If all tumors including primary and/or metastatic colorectal carcinoma were regarded as technically resectable, we performed surgical resection after the waiting period of 1 month. If they were unresctable, we repeated the regimen within the upper limit of 12 cycles. The primary endpoint was R0 resection rate. The secondary endpoints included safety, PFS, and OS.
Between May 2012 and May 2015, total 50 patients were enrolled to this trial in 14 centers. The induction was not done in 2 patients, who were excluded. The median age of the 48 patients was 62.5 (range: 45 to 79) including 36 men and 12 women. The median tumor number detected by CT before the induction was 12 (1 to 57). Although the experimental treatment was incomplete in 15 patients, the rates of complete and partial response were 0% and 63.6%, respectively. R0 and R1 resections were done with no mortality in 26 and 5 patients, respectively (R0 resection rate: 54.2%), whereas surgery was abandoned in 2. Under the median follow-up of 1.5 years, the 1-year PFS was 51.7%, and 2-year OS was 71.5%.
For advanced CRLM with KRAS wild, mFOLFOX with cetuximab induction therapy was safely done and provided the sufficient R0 resection rate. This strategy can be effective to improve prognosis, which will be evaluated by further follow-up.
Clinical trial identification
UMIN Clinical Trials Registry; C000007923
Legal entity responsible for the study
The Institutiona Review Board of each participating institutions
All authors have declared no conflicts of interest.