Background: Hepatic recurrence occurs in a high rate after hepatectomy for patients with colorectal metastasis to the liver. Therefore, hepatic arterial infusion chemotherapy (HAI) has been applied
as an adjuvant therapy after hepatectomy. However, HAI is less effective against extra-hepatic recurrence. Antineoplastons (AS2-1 and A10) are naturally occurring peptides and amino acid
derivatives found in human blood and urine. Sodium phenylacetate is the main component of AS2-1 and A10. The small peptides reportedly control neoplastic growth and have minimum adverse effects. It
seems to be reasonable to apply systemic administration of antineoplastons in addition to HAI after hepatectomy in colorectal metastasis to the liver. This randomized phase II study compares the
efficacy of hepatic arterial infusion with or without antineoplastons as postoperative adjuvant therapy for colorectal metastasis to the liver. Patients and Methods: A total of 65 patients who
underwent hepatectomy, thermal ablation or their combination for liver metastases from colorectal cancer enrolled between 1998 and 2004 from Kurume University hospital. The patients were randomly
assigned to receive systemic antineoplastons (infusion A10 followed by peroral AS2-1) plus HAI using 5-fluorouracil (group A) or HAI alone (group B) by the number of metastases and presence of
extra-hepatic metastasis at the time of or before operation. The primary endpoint was mode and extent of recurrence, and secondary endpoints were cancer-specific survival, disease-free survival,
rate of re-surgical treatment and adverse effects. Results: Thirty two patients were randomly assigned to group A and 33 to group B. The cancer-specific survival rate in the group A was higher than
that in the group B. Although the disease-free survival rates were similar between the groups, the rate of single organ recurrence and re-surgical treatment was higher in the group A. In addition,
the extent of recurrent tumors in the group A tended to be within re-surgical treatment. The major adverse effects of antineoplastons were fullness of the stomach and phlebitis. However, no
additional toxicity such as bone marrow suppression, liver dysfunction and renal dysfunction was found in the group A. Conclusion: Antineoplastons appears to be useful as an adjuvant therapy in
addition to hepatic arterial infusion after hepatectomy in colorectal metastases to the liver.