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Pyrazoloacridine for the treatment of hormone-refractory prostate cancer
E J Small1, L J Fippin, S P Whisenant
1Department of Medicine, University of California, San Francisco, USA. eric_small@quickmail.ucsf.edu
Abstract:
There is a pressing need for new agents for the treatment of hormone-resistant prostate cancer (HRPC). Pyrazoloacridine (PZA) has antitumor activity in several in vitro and in vivo tumor systems, and was selected for testing in clinical trials by the National Cancer Institute (NCI). We conducted a phase II trial of PZA for the treatment of HRPC. Seventeen male patients with HRPC were treated with PZA at 750 mg/m2 i.v. given over a period of 3 hr every 3 weeks. Response to therapy was assessed with serial measurements of serum prostate-specific antigen (PSA) and sequential imaging studies. The 17 patients were treated and fully evaluable. One patient experienced a significant decrease in PSA, from over 10,000 ng/ml to 423 ng/ml, along with an improvement in bone scan findings. However, no other patient obtained an objective or PSA response (overall PSA response rate = 5.9%). Median survival duration was 15.3 months. Toxicity was moderate. If PSA is used as a marker of response, single-agent PZA appears to lack efficacy in the treatment of HRPC. However, the one unambiguous response, and the favorable toxicity profile observed, may warrant further evaluation of this agent.
Insights
Pyrazoloacridine (PZA) showed limited efficacy in treating hormone-resistant prostate cancer (HRPC), with only one patient responding. Further evaluation of PZA may be warranted due to its favorable toxicity profile.
Area of Science:
- Oncology
- Pharmacology
Background:
- Hormone-resistant prostate cancer (HRPC) requires novel therapeutic agents.
- Pyrazoloacridine (PZA) exhibits antitumor activity and was selected for clinical trials by the National Cancer Institute (NCI).
Purpose of the Study:
- To evaluate the efficacy and toxicity of single-agent Pyrazoloacridine (PZA) in patients with hormone-resistant prostate cancer (HRPC).
Main Methods:
- A phase II clinical trial was conducted involving 17 male patients with HRPC.
- Patients received PZA at 750 mg/m2 intravenously every 3 weeks.
- Response was assessed using serum prostate-specific antigen (PSA) levels and imaging studies.
Main Results:
- One patient achieved a significant PSA decrease and improved bone scan findings.
- The overall PSA response rate was 5.9%, with no other objective responses observed.
- Median survival was 15.3 months, and toxicity was moderate.
Conclusions:
- Single-agent PZA demonstrates limited efficacy in treating HRPC when PSA is the response marker.
- The single unambiguous response and acceptable toxicity suggest potential for further investigation of PZA.