Hepatic resection is known to be the standard treatment for patients with colorectal liver metastasis (CRLM). The recent advancement in chemotherapy has led to the extended surgical indication and better outcome in patients with advanced CRLM. This phase II trial was designed to prospectively evaluate the validity of induction chemotherapy using mFOLFOX with cetuximab for advanced CRLM, which has been reported to provide early tumor shrinkage in CRLM with KRAS wild type.
Patients having advanced CRLM (tumor number > =5 and/or technically unresectbale) with KRAS wild type were included to this study. The induction of mFOLFOX with cetuximab was followed by the evaluation of surgical indication every 4 cycles (2 months). If all the tumors were regarded as technically resectable, we performed surgical resection after the waiting period of 1 month and postoperative chemotherapy was added until 12 cycles in total. If they were unresctable, we continued the regimen within the upper limit of 12 cycles. The primary endpoint was R0 resection rate. The secondary endpoints included recurrence free survival (RFS), progression free survival (PFS), and overall survival (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). R0 and R1 resections were performed in 26 and 5 patients, respectively (R0 resection rate: 54.2%), and there was no mortality. Under the median follow-up of 2.5 years, the 3-year RFS was 14.4%, 3-year PFS was 8.2%, 3-year OS was 60.0%, and median survival time was 3.4year.
For advanced CRLM with KRAS wild type, mFOLFOX with cetuximab induction therapy provided the sufficient R0 resection rate and favorable outcome.
Clinical trial identification
UMIN Clinical Trials Registry; C000007923.
Legal entity responsible for the study
The Institutional Review Board of each participating institutions.
Has not received any funding.
All authors have declared no conflicts of interest.