The overall response rate was 33% and the median survival was 13 months. In a small study reported by Mancuso et al. (44), patients treated with continuous HAI oxaliplatin (20 mg/m2/day × 5 days) alone showed a response rate of 46%, similar to response rates reported for HAI FUDR as monotherapy. Guthoff et al. (12) reported an overall response rate of 80% for patients treated with HAI using oxaliplatin in combination with 5-FU/LV and mitomycin C. Boige et al. (37) investigated

the activity of HAI oxaliplatin Inhibitors,research,lifescience,medical (100 mg/m2 over 2 hours) in combination with systemic 5-FU/LV in second-line chemoBuparlisib therapy for colorectal liver metastases previously treated with FOLFIRI (5-FU, LV and irinotecan), FOLFOX (5-FU, LV, and oxaliplatin), or both. They observed a response rate of 62%, which led to R0 resection or radiofrequency ablation in 18% of patients. A newer prospective study at MSKCC randomized patients to receive

Bevacizumab in combination with HAI FUDR and systemic Inhibitors,research,lifescience,medical therapy. Of the chemo naïve patients on the non Bev arm, 67% were converted to resectable status. These studies strongly suggest that HAI therapy should be considered as chemotherapy in the second-line treatment of patients with colorectal liver metastases (Table 2). With the addition of HAI, patients are more likely to undergo liver resection even after having failed first-line therapy. Table 2 Inhibitors,research,lifescience,medical Combination of hepatic arterial infusion with newer systemic chemotherapy Inhibitors,research,lifescience,medical in the second-line treatment of unresectable liver metastases from colorectal cancer. Is there a role for HAI in adjuvant treatment after hepatic resection? Although resection of colorectal

liver metastases remains the only curative option, nearly 70% of patients develop recurrence after surgery, which occurs Inhibitors,research,lifescience,medical most commonly within two years. Thus, there is a rationale for adjuvant chemotherapy after liver resection. Adjuvant systemic chemotherapy with 5-FU/LV showed an increase in disease-free but not overall survival (45,46). FOLFIRI did not significantly improve outcomes compared with 5-FU/LV (47). There is no randomized data supporting the use of adjuvant FOLFOX or another oxaliplatin-based Calpain chemotherapy after liver resection. In the light of these data the determination of an optimal adjuvant systemic chemotherapy regimen is unclear (48). Since the majority of recurrences occur in the liver, HAI therapy after liver resection is an option for patients with CRC. Implantation of the HAI pump can be done in conjunction with liver resection. Early randomized studies comparing HAI plus or minus systemic 5-FU-based chemotherapy after liver resection showed that combined therapy significantly improved disease-free survival (49-52). Other studies suggest that modern systemic chemotherapy (i.e., irinotecan and oxaliplatin) and HAI can be safely integrated in order to achieve better overall outcomes (Table 3).