Irofulven demonstrates clinical activity against metastatic hormone-refractory prostate cancer in a phase 2 single-agent trial.

Abstract

BACKGROUND:

The primary objective of this study was to assess the antitumor activity of irofulven in patients with hormone-refractory prostate cancer by measuring a sustained decrease of 50% or greater in serum prostate-specific antigen (PSA) levels.

PATIENTS AND METHODS:

Forty-two patients (median age, 73 years) received at least 1 dose of 10.6 mg/m2 irofulven per day on days 1-5 of a 28-day course. Eligible patients had pathologically confirmed metastatic hormone-refractory adenocarcinoma of the prostate and had not received prior cytotoxic chemotherapy.

RESULTS:

Forty-two patients received a median of 3 courses of irofulven. Thirty-two patients received at least 2 courses of therapy and were evaluable for efficacy. Four patients (13%) achieved partial response, with a median duration of 2.9 months (range, 2.6-5.8 months). Twenty-seven patients (84%) had disease stabilization and 1 patient (3%) progressed on study. Median progression-free survival was 3.2 months (95% confidence interval, 2.3-4.2 months), with a median progression-free survival of 4.2 months (range, 3.5-6.9 months) for responders. Grade 4 toxicities consisted of thrombocytopenia, anemia, and neutropenia, occurring in 1 patient each. The most common treatment-related grade 3 nonhematologic toxicities included asthenia (19% of patients), vomiting (14%), nausea (12%), and infection without grade 3/4 neutropenia (10%).

CONCLUSION:

Irofulven shows activity in hormone-refractory prostate cancer and has an acceptable safety profile, warranting further investigation of this drug, particularly in combination therapies.

• Authors: Neil Senzer, James Arsenau, Donald Richards, Barry Berman, John R MacDonald, Sheri Smith
• Journal: American journal of clinical oncology (Am J Clin Oncol) Vol. 28 Issue 1 Pg. 36-42 (Feb 2005) ISSN: 1537-453X [Electronic] United States
• PMID: 15685033 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Alkylating
• Sesquiterpenes
• irofulven
• Prostate-Specific Antigen

Topics

• Adenocarcinoma (blood, drug therapy, secondary)
• Aged
• Aged, 80 and over
• Antineoplastic Agents, Alkylating (therapeutic use)
• Humans
• Male
• Middle Aged
• Prostate-Specific Antigen (blood)
• Prostatic Neoplasms (blood, drug therapy, pathology)
• Sesquiterpenes (therapeutic use)
• Survival Analysis