A PHASE-II STUDY OF 5-AZA-2'DEOXYCYTIDINE (DECITABINE) IN HORMONE-INDEPENDENT METASTATIC (D2) PROSTATE-CANCER

Aims and Background: Decitabine (5-aza-2'-deoxycytidine) is an S-phase -specific pyrimidine analog with hypomethylation properties. In labora tory models of prostate cancer (PC-3 and DU-145), decitabine induces c ellular differentiation and enhanced expression of genes involved in t umor suppression, immunogenicity, and programmed cell death, Methods: We conducted a phase lr study of decitabine in 14 men with progressive , metastatic prostate cancer recurrent after total androgen blockade a nd flutamide withdrawal. Decitabine was administered at a dose of 75 m g/m(2)/dose IV as a 1 hour infusion every 8 hours for three doses. Cyc les of therapy were repeated every 5 to 8 weeks to allow for resolutio n of toxicity. Results: Two of 12 patients evaluable for response had stable disease with a time to progression of more than 10 weeks. This activity was seen in 2 of 3 African-American patients. Toxicity was si milar to previously reported experience. No significant changes in uri nary concentrations of the angiogenic factor bFGF, a potential biomark er of tumor activity, were identified over time in 7 unselected patien ts with progressive disease, Conclusions: We conclude that decitabine is a well tolerated regimen with modest clinical activity against horm one-independent prostate cancer. Further investigations in patients of African-American origin may be warranted.