Abstract | BACKGROUND: The safety, tolerability, and pharmacokinetic and preliminary efficacy of PCK3145 were determined in patients with metastatic hormone-refractory prostate cancer. PATIENTS AND METHODS:
PCK3145 was administered in ascending doses of 5, 20, 40, and 80 mg/m2 3 times per week for 4 weeks to cohorts of 4 patients. Dose escalation was based on dose-limiting toxicity (DLT). Pharmacokinetic profiles, tumor burden, and tumor markers (including prostate-specific antigen [PSA] and matrix metalloproteinase-9 [ MMP-9] levels) were assessed. Sixteen patients received PCK3145. The median age was 66 years, and the median PSA level was 232.5 microg/L. A total of 32 cycles of therapy were administered. RESULTS: The most common adverse events reported were pain and nausea. The only DLT was a grade 4 cardiac arrhythmia in a patient treated at the 80-mg/m2 dose level. Pharmacokinetic analysis using a 2-compartment model indicated that the mean area under the curve values increased as the dose range increased, and the mean elimination half-life ranged from 0.35 hours to 1.45 hours. The best tumor response was stable disease in 10 patients and progressive disease in 5 patients. No PSA responses were observed, but 1 patient showed a marked reduction in PSA of 41% at cycle 2. A substantial reduction in MMP-9 levels was observed in patients with baseline levels of MMP-9 > 100 microg/L. CONCLUSION:
PCK3145 was safe and well tolerated at all doses. Efficacy observations were encouraging, and the biologic activity of PCK3145 in reducing MMP-9 level may suggest a potential role of this peptide in the regulation of metastatic tumor growth.
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Authors | Robert E Hawkins, Luc Daigneault, Richard Cowan, Richard Griffiths, Chandra Panchal, Anne Armstrong, Jackie Fenemore, Alan Irvine, Kasia Sereda, Hélène Dulude |
Journal | Clinical prostate cancer
(Clin Prostate Cancer)
Vol. 4
Issue 2
Pg. 91-9
(Sep 2005)
ISSN: 1540-0352 [Print] United States |
PMID | 16197609
(Publication Type: Clinical Trial, Journal Article)
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Chemical References |
- Antineoplastic Agents
- Peptide Fragments
- Prostatic Secretory Proteins
- tigapotide
- Matrix Metalloproteinase 9
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Topics |
- Adenocarcinoma
(drug therapy, secondary)
- Aged
- Antineoplastic Agents
(adverse effects, pharmacokinetics, therapeutic use)
- Humans
- Male
- Matrix Metalloproteinase 9
(metabolism)
- Middle Aged
- Peptide Fragments
(adverse effects, pharmacokinetics, therapeutic use)
- Prostatic Neoplasms
(drug therapy, metabolism, pathology)
- Prostatic Secretory Proteins
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