title: Phase I/II study of intraperitoneal mitoxantrone in refractory ovarian cancer.
abstract: BACKGROUND
  Mitoxantrone has demonstrable clinical activity when administered intravenously in a wide range of malignancies. The feasibility and toxicity of intra-peritoneal administration was established in a phase I study. The optimal dose from the phase I was subsequently evaluated in a phase II study.
  
  
  METHODS
  19 patients with refractory malignancies and extensive abdominal disease (13 ovarian cancer, 4 breast cancer, 2 mesothelioma) were entered in a phase I study. The dose of intraperitoneal mitoxantrone was escalated from 10 mg/m2, administered in 21 of fluid via a Tenckhoff catheter, to 55 mg/m2, in increments of 5 mg/m2. Cycles were repeated every three weeks. Sixty-seven cycles of mitoxantrone were administered, the maximum tolerable dose being 25 mg/m2. A phase II study at this dose was conducted in 14 patients with refractory ovarian cancer, all of whom had previously received systemic platinum based therapy. Five of the 14 had also previously been treated with intraperitoneal carboplatin. Fifty-one cycles were administered.
  
  
  RESULTS
  The dose limiting toxicity in the phase I study was peritoneal irritation and pain. Leucopenia was frequent at doses equal or greater than 30 mg/m2. Three complete remissions were documented in the phase I study (2 breast cancer and 1 ovarian cancer). There was no significant haematological toxicity in the phase II assessment, though local toxicity precluded further therapy in 2 patients. No objective responses were seen in the phase II evaluation.
  
  
  CONCLUSIONS
  These studies demonstrate the feasibility of intra-peritoneal mitoxantrone therapy in patients with peritoneal disease, but do not support its routine use in ovarian cancer.
authors.affiliation: Antoni van Leeuwenhoel Ziekenhuis, Netherlands Cancer Institute, Amsterdam.
authors.forename: A M
authors.initials: AM
authors.lastname: Oza
authors.forename: W
authors.initials: W
authors.lastname: ten Bokkel Huinink
authors.forename: R
authors.initials: R
authors.lastname: Dubbelman
authors.forename: O
authors.initials: O
authors.lastname: Soepenberg
authors.forename: I
authors.initials: I
authors.lastname: Mandjes
authors.forename: E
authors.initials: E
authors.lastname: Aartsen
authors.forename: J G
authors.initials: JG
authors.lastname: McVie
mesh_terms: D015746:Abdominal Pain / Q000139:chemically induced; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007274:Injections, Intraperitoneal; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010538:Peritonitis / Q000139:chemically induced; D011379:Prognosis; D014839:Vomiting / Q000139:chemically induced
chemical_list: D008942:Mitoxantrone