A phase II study of irofulven in women with recurrent and heavily pretreated ovarian cancer.

Abstract

OBJECTIVE:

To determine the safety and efficacy of a novel illudin S derivative, irofulven (MGI-114), in patients with recurrent ovarian cancer who had received extensive prior chemotherapy.

METHODS:

The trial was an open label phase II study. Patients initially enrolled in this study were treated every 14 days with a dose of 24 mg/m2. Unexpected retinal toxicity associated with this dose and schedule lead to modification of the dosing to 0.55 mg/kg on the same schedule with a maximum individual dose of 50 mg. Dose reductions were permitted based on both hematologic and non-hematologic toxicities.

RESULTS:

Seventy-four women were accrued and stratified into two cohorts including 58 women with platinum-resistant disease and 16 with platinum-sensitive disease. Non-hematologic toxicities included nausea, vomiting, and fatigue. Thirty-one women had between one and six visual symptoms, most were Grade 1 and 2 in nature. The majority of visual toxicities resolved either during treatment or post-treatment with irofulven. There was one partial response in each cohort with 19 (33%) and 8 (50%) of women having stable disease in the platinum-resistant and platinum-sensitive cohorts, respectively.

CONCLUSIONS:

Irofulven at 24 mg/m2 on every 14-day schedule is associated with significant retinal toxicity in this patient population. Dosing at 0.55 mg/kg has persistent retinal toxicity, yet demonstrated only limited anti-tumor activity in a population of women who had received extensive prior chemotherapy.

• Authors: Michael V Seiden, Alan N Gordon, Diane C Bodurka, Ursula A Matulonis, Richard T Penson, Eddie Reed, Dave S Alberts, Garry Weems, Michael Cullen, William P McGuire 3rd
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 101 Issue 1 Pg. 55-61 (Apr 2006) ISSN: 0090-8258 [Print] United States
• PMID: 16260029 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Alkylating
• Organoplatinum Compounds
• Sesquiterpenes
• irofulven

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents, Alkylating (adverse effects, therapeutic use)
• Cohort Studies
• Drug Resistance, Neoplasm
• Female
• Humans
• Infusions, Intravenous
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy)
• Organoplatinum Compounds (pharmacology)
• Ovarian Neoplasms (drug therapy)
• Sesquiterpenes (adverse effects, therapeutic use)