title: Phase II study of azacitidine to restore responsiveness of prostate cancer to hormonal therapy.
abstract: Epigenetic alterations, including methylation of key tumor suppressor genes, may play a role in the progression of prostate cancer to a castration-refractory state. Azacitidine, an agent approved for the treatment of myelodysplastic syndromes, appears to exert its antineoplastic effects partly by hypomethylating DNA that leads to the reversal of gene silencing. It is hypothesized that the addition of azacitidine to complete androgen blockade may restore the responsiveness of progressive prostate cancer to hormonal therapy. A phase II trial was designed to evaluate the activity of azacitidine to primarily modulate PSA kinetics, with supportive secondary clinical endpoints. Correlative studies will be performed to detect the biologic activity of azacitidine (increased fetal hemoglobin, plasma DNA methylation) and examine any association with anti-tumor clinical activity.
authors.affiliation: US Oncology Research, Inc., 501 Medical Center Blvd, Webster, TX 77598, USA. guru.sonpavde@usoncology.com
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
authors.forename: Ana
authors.initials: A
authors.lastname: Aparicio
authors.forename: Israel
authors.initials: I
authors.lastname: Guttierez
authors.forename: Kristi A
authors.initials: KA
authors.lastname: Boehm
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Hutson
authors.forename: William R
authors.initials: WR
authors.lastname: Berry
authors.forename: Lina
authors.initials: L
authors.lastname: Asmar
authors.forename: Daniel D
authors.initials: DD
authors.lastname: von Hoff
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001374:Azacitidine / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy*
chemical_list: D000726:Androgen Antagonists; D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine