Randomized Phase II Study of 5-Fluorouracil Hepatic Arterial Infusion with or without Antineoplastons as an Adjuvant Therapy after Hepatectomy for Liver Metastases from Colorectal Cancer

Abstract

BackgroundAntineoplastons are naturally occurring peptides and amino acid derivatives found in human blood and urine. Antineoplaston A10 and AS2-1 reportedly control neoplastic growth and do not significantly inhibit normal cell growth. Antineoplastons contain 3-phenylacetylamino-2, 6-piperidinedione (A10), phenylacetylglutamine plus phenylacetylisoglutamine (A10-I), and phenylacetylglutamine plus phenylacetate (AS2-1). This open label, non- blinded randomized phase II study compared the efficacy of hepatic arterial infusion (HAI) with 5-fluorouracil,with or without antineoplastons as a postoperative therapy for colorectal metastasis to the liver.MethodsSixty-five patients with histologically confirmed metastatic colon adenocarcinoma in liver, who had undergone hepatectomy, and/or thermal ablation for liver metastases were enrolled between 1998- 2004 in Kurume University Hospital. Patients were randomly assigned to receive systemic antineoplastons (A10-I infusion followed by per-oral AS2-1) plus HAI (AN arm) or HAI alone (control arm) based on the number of metastases and presence/ absence of extra-hepatic metastasis at the time of surgery. Primary endpoint was cancer-specific survival (CSS); secondary endpoints were relapse-free survival (RFS), status and extent of recurrence, salvage surgery (rate) and toxicity.FindingsOverall survival was not statistically improved (p=0.105) in the AN arm (n=32). RFS was not significant (p=0.343). Nevertheless, the CSS rate was significantly higher in the AN arm versus the control arm (n=33) with a median survival time 67 months (95%CI 43-not calculated) versus 39 months (95%CI 28-47) (p=0.037) and 5 year CSS rate 60% versus 32% respectively. Cancer recurred more often in a single organ than in multiple organs in the AN arm versus the control arm. The limited extent of recurrent tumours in the AN arm meant more patients remained eligible for salvage surgery. Major adverse effects of antineoplastons were fullness of the stomach and phlebitis. No serious toxicity, including bone marrow suppression, liver or renal dysfunction, were found in the AN arm.InterpretationAntineoplastons (A10 Injection and AS2-1) might be useful as adjunctive therapy in addition to HAI after hepatectomy in colorectal metastases to the liver.Trial registration informationClinicalTrials.gov UMIN000012099

5-Fluorouracil induces apoptosis of colorectal cancer cells

“…Patients often experience indigestion, abdominal distention and pain, edema, jaundice, and supraclavicular lymph node swelling (Peng et al, 2015). Treatments for colorectal cancer include surgical resection, chemotherapy, immunotherapy, or a combination of these methods (Ogata et al, 2015).…”

“…However, its effectiveness is limited in elderly patients or cardiovascular disease patients, for whom chemotherapy is an alternative choice (Ogata et al, 2015). 5-Fluorouracil (5-FU) is the most widely used chemotherapy drug for the treatment of colorectal cancer (Ogata et al, 2015) and is an effective cancer treatment (Yashima et al, 2015).…”

Hepatic arterial infusion plus systemic chemotherapy as third-line or later treatment in colorectal liver metastases

“…While the majority of patients initially respond to first-and second-line SCT (e.g. those combining 5-fluorouracil (5-FU) with irinotecan, oxaliplatin and, lately, biologic agents [6], the disease will eventually progress and become resistant to anticancer drugs. For this reason, patients with highly advanced unresectable CLMs may be forced to undergo multiple lines of treatment.…”

A Phase II Study of Antineoplastons A10 and AS2-1 in Adult Patients with Primary Brain Tumors—Final Report (Protocol BT-09)

“…Among the initial protocols, BT-09 and BT-10 were designed for different types of primary brain tumors which were not curable by standard treatment in adults (BT-09) and children (BT-10). Numerous additional protocols dealt with the treatment of specific types of brain tumors in children and adults and colorectal cancer [4]- [18]. The aim of this single arm study is to assess the efficacy and safety of ANP in adults who have different types of incurable primary brain tumors.…”