A phase II study of 5-aza-2'deoxycytidine (decitabine) in hormone independent metastatic (D2) prostate cancer

Alain Thibault, William D. Figg, Raymond C. Bergan, Richard M. Lush, Charles E. Myers, Anne Tompkins, Eddie Reed, Dvorit Samid

Research output: Contribution to journalArticlepeer-review

117 Scopus citations

Abstract

Aims and Background: Decitabine (5-aza-2'-deoxycytidine) is an S-phase- specific pyrimidine analog with hypomethylation properties. In laboratory models of prostate cancer (PC-3 and DU-145), decitabine induces cellular differentiation and enhanced expression of genes involved in tumor suppression, immunogenicity, and programmed cell death. Methods: We conducted a phase II study of decitabine in 14 men with progressive, metastatic prostate cancer recurrent after total androgen blockade and flutamide withdrawal. Decitabine was administered at a dose of 75 mg/m2/dose IV as a I hour infusion every 8 hours for three doses. Cycles of therapy were repeated every 5 to 8 weeks to allow for resolution of toxicity. Results: Two of 12 patients evaluable for response had stable disease with time to progression of more than 10 weeks. This activity was seen in 2 of 3 African-American patients. Toxicity was similar to previously reported experience. No significant changes in urinary concentrations of the angiogenic factor bFGF, a potential biomarker of tumor activity, were identified over time in 7 unselected patients with progressive disease. Conclusions: We conclude that decitabine is a well tolerated regimen with modest clinical activity against hormone-independent prostate cancer. Further investigations in patients of African-American origin may be warranted.

Original languageEnglish (US)
Pages (from-to)87-89
Number of pages3
JournalTumori
Volume84
Issue number1
DOIs
StatePublished - 1998
Externally publishedYes

Keywords

  • Angiogenesis
  • bFGF
  • Chemotherapy
  • Malignancy
  • Tumor biology
  • Tumor markers

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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