A phase II study of irofulven in women with recurrent and heavily pretreated ovarian cancer.
Gynecol Oncol. 2005 Oct 28; [Epub ahead of print]
Seiden MV, Gordon AN, Bodurka DC, Matulonis UA, Penson RT, Reed E, Alberts DS, Weems G, Cullen M, McGuire WP 3rd.
Gynecologic Oncology Research Program at Dana Farber/Partners Cancer Care Program, Boston, MA 02115, USA; The Division of Hematology Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.
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/m(2). 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/m(2) 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. |
