title: Combination therapy of recurrent prostate cancer with the proteasome inhibitor bortezomib plus hormone blockade.
abstract: A single arm phase II trial of single-agent bortezomib (BZM) alone or combined with hormone blockade was conducted in patients with early PSA recurrence after definitive local therapy. The primary endpoint of this study was to determine the time to PSA relapse after BZM therapy alone or when BZM was combined with hormone blockade. The secondary endpoint was to determine the safety of combination therapy. Part A of the treatment schedule consisted of three cycles of BZM 1.3 mg/m2 IV given on days 1,4,8,11. If patients progressed on Part A, they were entered on Part B which consisted of a single dose of LH-RH antagonist, daily oral antiandrogen, and weekly BZM 1.3 mg/m2 for three out of four weeks for a total of three months. BZM treatment significantly decreased the slope of the log PSA (p=0.024) demonstrating that this agent alone was capable of slowing the rise of the PSA. Of eight patients treated with BZM alone five had stable disease, two progressed and 1 went off study secondary to toxicity. The major toxicity was neurotoxicity requiring discontinuation of therapy in three patients and treatment interruption in nine patients. Of those receiving Parts A and B or B only, there were 11 of 15 CRs with the average time to progression of 5.5 months. BZM treatment can change the slope of PSA rise and can be combined with hormone deprivation therapy without significant additional side effects; these agents are associated with a median time to CR of 42 days.
authors.affiliation: Hollings Cancer Center, Medical University of South Carolina, Charleston SC USA. Kraft@musc.edu
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Kraft
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Garrett-Mayer
authors.forename: Amy E
authors.initials: AE
authors.lastname: Wahlquist
authors.forename: Ali
authors.initials: A
authors.lastname: Golshayan
authors.forename: Chien-Shing
authors.initials: CS
authors.lastname: Chen
authors.forename: William
authors.initials: W
authors.lastname: Butler
authors.forename: James
authors.initials: J
authors.lastname: Bearden
authors.forename: Michael
authors.initials: M
authors.lastname: Lilly
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D015853:Cysteine Proteinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000726:Androgen Antagonists; D001897:Boronic Acids; D015853:Cysteine Proteinase Inhibitors; D011719:Pyrazines; D007987:Gonadotropin-Releasing Hormone; D000069286:Bortezomib; D017430:Prostate-Specific Antigen