A phase II study of irofulven in women with recurrent and heavily pretreated ovarian cancer.
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.
Seiden
Michael V
MV
Gynecologic Oncology Research Program at Dana Farber/Partners Cancer Care Program, Boston, MA 02115, USA. mseiden@partners.org
Gordon
Alan N
AN
Bodurka
Diane C
DC
Matulonis
Ursula A
UA
Penson
Richard T
RT
Reed
Eddie
E
Alberts
Dave S
DS
Weems
Garry
G
Cullen
Michael
M
McGuire
William P
WP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D012717:Sesquiterpenes / Q000009:adverse effects / Q000627:therapeutic use*
D018906:Antineoplastic Agents, Alkylating; D009944:Organoplatinum Compounds; D012717:Sesquiterpenes; C102714:irofulven