title: 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: BACKGROUND
  Antineoplastons 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.
  
  
  METHODS
  Sixty-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.
  
  
  RESULTS
  Overall 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.
  
  
  CONCLUSIONS
  Antineoplastons (A10 Injection and AS2-1) might be useful as adjunctive therapy in addition to HAI after hepatectomy in colorectal metastases to the liver.
  ClinicalTrials.gov UMIN000012099.
authors: Department of Surgery, Kurume University Medical Center, Kurume, Japan.
authors: Yutaka
authors: Y
authors: Ogata
authors: Departments of Surgery, Kurume University School of Medicine, Kurume, Japan.
authors: Keiko
authors: K
authors: Matono
authors: Kurume Daiichi Social Insurance Hospital, Kurume, Japan.
authors: Hideaki
authors: H
authors: Tsuda
authors: Departments of Surgery, Kurume University School of Medicine, Kurume, Japan.
authors: Masataka
authors: M
authors: Ushijima
authors: Department of Surgery, Kurume University Medical Center, Kurume, Japan.
authors: Shinji
authors: S
authors: Uchida
authors: Departments of Surgery, Kurume University School of Medicine, Kurume, Japan.
authors: Yoshito
authors: Y
authors: Akagi
authors: Departments of Surgery, Kurume University School of Medicine, Kurume, Japan.
authors: Kazuo
authors: K
authors: Shirouzu
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D044482:Benzeneacetamides / Q000008:administration & dosage / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant / Q000379:methods; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000601:surgery; D004338:Drug Combinations; D005472:Fluorouracil / Q000008:administration & dosage* / Q000627:therapeutic use; D005973:Glutamine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D006498:Hepatectomy; D006801:Humans; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary* / Q000601:surgery; D008875:Middle Aged; D010648:Phenylacetates / Q000008:administration & dosage / Q000627:therapeutic use; D010881:Piperidones / Q000008:administration & dosage / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D044482:Benzeneacetamides; D004338:Drug Combinations; D010648:Phenylacetates; D010881:Piperidones; D005973:Glutamine; C092038:antineoplaston AS 2-1; C052091:antineoplaston A10; D005472:Fluorouracil