title: Phase II trial of weekly or biweekly intraperitoneal mitoxantrone in epithelial ovarian cancer.
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 less than or equal to 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).
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
authors.forename: M
authors.initials: M
authors.lastname: Markman
authors.forename: T
authors.initials: T
authors.lastname: Hakes
authors.forename: B
authors.initials: B
authors.lastname: Reichman
authors.forename: J L
authors.initials: JL
authors.lastname: Lewis
authors.forename: S
authors.initials: S
authors.lastname: Rubin
authors.forename: W
authors.initials: W
authors.lastname: Jones
authors.forename: L
authors.initials: L
authors.lastname: Almadrones
authors.forename: W
authors.initials: W
authors.lastname: Hoskins
mesh_terms: D000328:Adult; D000368:Aged; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007274:Injections, Intraperitoneal; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000009:adverse effects; D009364:Neoplasm Recurrence, Local; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D011379:Prognosis; D015996:Survival Rate
chemical_list: D008942:Mitoxantrone