Phase II trial of weekly or biweekly intraperitoneal mitoxantrone in epithelial ovarian cancer

Maurie Markman, Thomas Hakes, Bonnie Reichman, John L. Lewis, Stephen Rubin, Walter Jones, Lois Almadrones, William Hoskins

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Previous experimental and clinical evaluation has suggested that ovarian cancer is sensitive to the cytotoxic effects of mitoxantrone at concentrations achievable within the peritoneal cavity after intraperitoneal (IP) administration. Unfortunately, the use of the drug delivered IP at high doses (20 mg/m2 in 2 L normal saline [NS]) on a monthly schedule is compromised by severe local effects secondary to the irritant properties of the drug. To reduce toxicity and take advantage of minimal systemic drug exposure following IP administration, we treated 28 patients with a lower drug concentration of mitoxantrone (10 mg/m2 in 2 L NS), but on a weekly or every other week schedule (total, 12 courses). Compared with the monthly program, this regimen caused less pain, allowed for a higher cumulative dose of mitoxantrone to be delivered, and resulted in less serious treatment-related morbidity. Four of 13 assessable patients (31%) whose largest tumor was ≤ 1 cm in diameter demonstrated a surgically defined response. All responding patients had failed previously or exhibited a minimal response to cisplatin. Despite the improved toxicity profile of this regimen, the overall response rate was similar to the monthly program, probably secondary to inadequate IP drug distribution in many patients. Future investigative efforts using IP mitoxantrone as therapy for ovarian cancer might focus on developing methods to improve drug delivery to all sites of tumor within the peritoneal cavity (eg, intraoperative therapy, increased treatment volumes, and antiinflammatory agents to reduce adhesion formation).

Original languageEnglish
Pages (from-to)978-982
Number of pages5
JournalJournal of Clinical Oncology
Volume9
Issue number6
DOIs
StatePublished - 1991

Keywords

  • Adult
  • Aged
  • Drug Administration Schedule
  • Drug Evaluation
  • Female
  • Follow-Up Studies
  • Humans
  • Injections, Intraperitoneal
  • Middle Aged
  • Mitoxantrone/administration & dosage
  • Neoplasm Recurrence, Local
  • Ovarian Neoplasms/drug therapy
  • Prognosis
  • Survival Rate

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