A PHASE I-II TRIAL OF MITOXANTRONE BY HEPATIC ARTERIAL INFUSION IN PATIENTS WITH HEPATOCELLULAR-CARCINOMA OR COLORECTAL-CARCINOMA METASTATIC TO THE LIVER

Background. Mitoxantrone is an anthraquinone derivative that has demon strated encouraging preclinical and clinical activity against a variet y of human carcinoma cell lines and malignancies. Three Phase II studi es of systemically administered mitoxantrone in patients with colorect al carcinoma failed to demonstrate any therapeutic activity, as did fo ur Phase II studies of intravenous mitoxantrone in hepatocellular carc inoma. Two additional trials demonstrated limited activity when admini stered intravenously to patients with hepatocellular carcinoma. Howeve r, because this drug exhibits a steep dose-response curve, a Phase I-I I trial of mitoxantrone by hepatic arterial infusion was initiated. Me thods. Patients with hepatocellular carcinoma and metastatic colorecta l carcinoma with liver only or liver-predominant disease were eligible for therapy. All patients underwent the placement of a percutaneous h epatic arterial catheter before each course of therapy, and the first cohort of patients was treated at 10 mg/m2/course on day 1 on a 28-day cycle. Dosages were escalated in increments of 2 mg/m2/course based o n side effects and tolerance. Results. Twenty-eight patients with bidi mensionally measurable unresectable, liver-predominant disease were en tered into this trial. The therapy was welt tolerated, with only 5 cou rses of 55 being complicated by neutropenia and none associated with f ever. Only one patient required a dosage reduction on the basis of tox icity (neutropenia). No complete or partial responses were observed. C onclusion. These data are consistent with a lack of therapeutic activi ty of mitoxantrone when administered by hepatic arterial infusion for the treatment of hepatocellular carcinoma or metastatic colorectal can cer.