In a phase II study, irofulven prolonged survival in men with hormone-refractory prostate cancer.


CHICAGO—Irofulven, a drug derived from a mushroom, may prolong survival in men with hormone-refractory prostate cancer (HRPC) who have failed treatment with docetaxel-based regimens, according to study findings presented here at the American Society of Clinical Oncology annual meeting.

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No commercially available treatments have been shown to prolong survival in this patient population. Irofulven improved survival by about 3.5 months compared with mitox-antrone plus prednisone, a finding that study investigator E. Roy Berger, MD, called “quite significant, especially in docetaxel failures.”


“The data support going forward with a Phase III study in patients with hormone-refractory metastatic prostate cancer who have failed first-line treatment with Taxotere,” said Dr. Berger, director of genitourinary research at North Shore Hematology/Oncology Associates in East Setauket, N.Y.


Irofulven is a semi-synthetic derivative of illudin S, one of a series of natural products isolated from the mushroom Omphalotus illudens. Irofulven inhibits DNA synthesis and causes cell cycle arrest in S phase, and induction of caspase-mediated apoptosis.


Prior monotherapy and combination Phase I/II trials with irofulven have shown anti-tumor effects in HRPC patients, including those who were resistant to docetaxel. 


Dr. Berger and his colleagues conducted an open-label, randomized international phase II study that included 137 men with HRPC resistant to docetaxel-based treatment. The men had a mean age of 64 years and median Gleason score of 8. Patients received either irofulven/prednisone (54 patients), irofulven/capecitabine/prednisone (56 patients) or mitoxantrone/prednisone (27 patients). All of the men were stratified according to baseline pain status. Efficacy end points included overall survival, time to progression (TTP), and PSA response.


Patients treated with irofulven/prednisone had a median survival of 10.6 months compared with 7.3 months for the patients who received mitoxantrone/prednisone. Median survival for patients treated with irofulven/capecitabine/prednisone was 9.4 months. The PSA response rates were 22% for the patients treated with irofulven/capecitabine/prednisone and 10% for patients treated with irofulven/prednisone. No PSA response was found in patients treated with mitoxantrone/prednisone.


Frequent Grade 3-4 toxicities were asthenia (8% for irofulven/prednisone, 15% for irofulven/capecitabine/prednisone and 0% for mitoxantrone/prednisone) and vomiting (4% for irofulven/prednisone, 11% for irofulven/capecitabine/prednisone and 0% for mitoxantrone/prednisone).


Grade 3-4 hematologic event was neutropenia (22% for irofulven/prednisone, 15% for irofulven/capecitabine/prednisone and 61% for mitoxantrone/predni-sone/prednisone, 21% for irofulven/capecitabine/prednisone, and 4% for mitoxantrone/prednisone).