A phase II study of 5-aza-2'deoxycytidine (decitabine) in hormone independent metastatic (D2) prostate cancer.
OBJECTIVE
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 i.v. as a 1 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 a 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.
Thibault
A
A
Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Figg
W D
WD
Bergan
R C
RC
Lush
R M
RM
Myers
C E
CE
Tompkins
A
A
Reed
E
E
Samid
D
D
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors*; D000077209:Decitabine; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D016222:Fibroblast Growth Factor 2 / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D004791:Enzyme Inhibitors; D016222:Fibroblast Growth Factor 2; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine