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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

129 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
Pages (from-to)87-89
Number of pages3
JournalTumori
Volume84
Issue number1
DOIs
StatePublished - 1998
Externally publishedYes

Keywords

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

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