Trial Information

Effect of Short-duration Preoperative Neoadjuvant Therapy With FOLFOX Based Therapy on Morbidity After Liver Resection for Colorectal Cancer Metastases

Although early stage, localized colon and rectal cancers are associated with 5 year survival
rates of nearly 90%, only a minority of patients present with localized disease.
Unfortunately, at the time of their initial presentation, approximately 35% of patients with
colon or rectal cancer have metastatic disease. Nearly two thirds of these patients with
stage IV disease have evidence of extrahepatic spread and have a median overall survival
rate of 8-10 months in the absence of further treatment. Even with the most intensive
chemotherapeutic regimens, the median overall survival for these patients ranges from 12
months to 20 months. However, a small subset of patients with stage IV disease has isolated
hepatic metastatic disease and can undergo resection. The patients with completely resected
liver metastases enjoy a significantly higher overall five-year survival, which is as high
as 58% in carefully selected patients. Ten-year overall survival has been reported in 22%
of patients. Despite this improvement, the five-year disease-free survival for these
patients is at best 35%, with hepatic recurrences occurring in 46%.

The fact that adjuvant chemotherapy improves the three-year survival rate for stage II
disease and five-year survival rates for stage III disease implies that it can treat
micrometastatic disease in some fraction of patients. Because micrometastatic disease is
likely the cause of the high recurrence rate in patients who undergo liver resection, there
is a clear biologic rationale for using postoperative adjuvant chemotherapy after liver
resection. Although this strategy is a common practice in many centers, no convincing data
that this improves survival have been reported. A large randomized phase III trial (EORTC
40983) examining this question is currently ongoing and effect on survival has not yet been
reported. Given that systemic chemotherapy after liver resection remains of unproven
benefit at the present time, many have wondered if preoperative treatment might have more
promise in improving recurrence rates.