title: A prospective phase II trial to evaluate the efficacy and toxicity of hepatic arterial infusion of ifosfamide in patients with inoperable localized hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is a common tumor in the developing countries. Most patients present with relatively advanced disease and have a poor survival. Due to lack of any effective therapy, there is an urgent need to investigate new drugs. We conducted a prospective trial to evaluate the efficacy and tolerability of ifosfamide (IFEX) in patients with histologically proved, inoperable, localized HCC. Eligibility criteria included World Health Organization (WHO) performance status (PS) of 0-2, bilirubin < or = 3.0 mg/dl, albumin > or = 2.5 g/dl, creatinine < or = 2.0 mg/dl, correctable coagulation profile, adequate bone marrow function, and no prior therapy. Hepatic arterial infusion of IFEX (6 g/m2) was given continuously over 96 hours. Mesna was given intravenously, in same doses, throughout IFEX infusion and for 12 hours afterwards. Nineteen patients were enrolled in the trial. Mean age was 51.1 years and all were men. Most of the patients had PS 1. The majority had viral hepatitis and cirrhosis. Eleven had raised serum alpha fetoprotein (AFP) levels. Thirteen patients had multiple lesions involving both lobes of the liver. Mean size of ultrasonographically evident largest lesion was 11.0 cm. Three patients are inevaluable; one died early, one refused further therapy, and another was lost to follow-up. Among the 16 evaluable patients, 6 (37.5%) had partial remission and 4 (25%) had a minor response. An additional four (25%) patients had stable disease. Only two (12.5%) patients had progression of disease while on therapy. Overall response rate (partial plus minor) was 62.5%. Mean duration of partial response was 5.0 months and mean survival was 7.1 months. Subjective improvement in pain was observed in all but two patients and correlated well with the objective response. Chemotherapy-related side effects were predominantly grade III-IV anemia and alopecia. Three patients had catheter-related complications (one local infection, one bleeding, and one thrombosis). Two patients developed mild encephalopathy and two had hepatic decompensation as evidenced by worsening liver function tests. The results of this pilot study suggest that IFEX, given as a continuous hepatic arterial infusion, is an active drug in inoperable localized HCC. Toxicity is manageable. This drug deserves further trials to properly evaluate its therapeutic potential.
authors.affiliation: Department of Medical Oncology, National Cancer Institute, Clifton, Karachi, Pakistan.
authors.forename: I A
authors.initials: IA
authors.lastname: Malik
authors.forename: W A
authors.initials: WA
authors.lastname: Khan
authors.forename: S
authors.initials: S
authors.lastname: Haq
authors.forename: M
authors.initials: M
authors.lastname: Sabih
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007069:Ifosfamide / Q000627:therapeutic use*; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012074:Remission Induction; D016879:Salvage Therapy / Q000379:methods*; D016019:Survival Analysis
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007069:Ifosfamide