Evaluation of irofulven (MGI-114) in the treatment of recurrent or persistent endometrial carcinoma: A phase II study of the Gynecologic Oncology Group.
OBJECTIVE
This multi-center phase II trial was conducted by the Gynecologic Oncology Group to evaluate the activity and toxicity of irofulven in patients with previously treated adenocarcinoma of the endometrium.


METHODS
Eligible patients had documented recurrent or persistent endometrial carcinoma after receiving definitive locoregional therapy, and were required to have measurable disease, performance status of 0-2, and adequate bone marrow, hepatic and renal functions prior to study entry. Patients were allowed one prior chemotherapy regimen. The initial dose of irofulven was 11 mg/m(2)/day for four days administered intravenously. Cycles were repeated every 28 days. Doses were escalated or reduced based on previous cycle toxicity.


RESULTS
Twenty-five patients were enrolled onto the trial. There was one (4%) confirmed complete response. Seven (28%) patients had stable disease, with a median duration of 10.4 (range: 4.4-21.6) months. Patients received a median of one (range: 1-5) cycle of protocol treatment. There were three early treatment-related deaths due to renal failure and severe electrolyte disturbances. Two patients experienced grade 4 hematologic adverse effects.


CONCLUSIONS
Irofulven administered at the dose and schedule used in this trial was minimally active and resulted in significant toxicity.
Schilder
Russell J
RJ
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Blessing
John A
JA
Pearl
Michael L
ML
Rose
Peter G
PG
D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D016889:Endometrial Neoplasms / Q000188:drug therapy*; D005260:Female; D006402:Hematologic Diseases / Q000209:etiology; D006801:Humans; D008875:Middle Aged; D009325:Nausea / Q000209:etiology; D009364:Neoplasm Recurrence, Local; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014839:Vomiting / Q000209:etiology
D018906:Antineoplastic Agents, Alkylating; D012717:Sesquiterpenes; C102714:irofulven