For hepatectomy after neoadjuvant chemotherapy (NAC), we applied circadian chronotherapy via the hepatic artery for multiple bilobar liver metastases from colorectal cancer. Four patients underwent chronotherapy and 16 patients underwent flat infusion therapy (5 day q 2 weeks, 4 or more courses). We used 2 drugs, (5-fluorouracil (5-FU) and l-leucovorin (l-LV)), and partially added cisplatin (CDDP) in the flat infusion group. The result was a higher response rate (75% vs 37.5%) and lower toxicity (0% vs 31.3%) in the chronotherapy group. Hepatectomy was performed on 12 of the 20 patients. The 5 responders to NAC showed better overall survival (p < 0.05) and lower remnant liver recurrence (p = 0.052) than the 7 non-responders. We therefore conclude that chronotherapy via the hepatic artery prior to hepatectomy may improve the survival of patients with multiple bilobar liver metastases.
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