HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Safety and tolerability of PCK3145, a synthetic peptide derived from prostate secretory protein 94 (PSP94) in metastatic hormone-refractory prostate cancer.

AbstractBACKGROUND:
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.
AuthorsRobert E Hawkins, Luc Daigneault, Richard Cowan, Richard Griffiths, Chandra Panchal, Anne Armstrong, Jackie Fenemore, Alan Irvine, Kasia Sereda, Hélène Dulude
JournalClinical prostate cancer (Clin Prostate Cancer) Vol. 4 Issue 2 Pg. 91-9 (Sep 2005) ISSN: 1540-0352 [Print] United States
PMID16197609 (Publication Type: Clinical Trial, Journal Article)
Chemical References
  • Antineoplastic Agents
  • Peptide Fragments
  • Prostatic Secretory Proteins
  • tigapotide
  • Matrix Metalloproteinase 9
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

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: