PMID- 25667107
OWN - NLM
STAT- MEDLINE
DCOM- 20160421
LR  - 20240213
IS  - 1476-5608 (Electronic)
IS  - 1365-7852 (Print)
IS  - 1365-7852 (Linking)
VI  - 18
IP  - 2
DP  - 2015 Jun
TI  - Prospective evaluation of low-dose ketoconazole plus hydrocortisone in docetaxel 
      pre-treated castration-resistant prostate cancer patients.
PG  - 144-8
LID - 10.1038/pcan.2015.2 [doi]
AB  - BACKGROUND: Ketoconazole is a well-known CYP17-targeted systemic treatment for 
      castration-resistant prostate cancer (CRPC). However, most of the published data 
      has been in the pre-chemotherapy setting; its efficacy in the post-chemotherapy 
      setting has not been as widely described. Chemotherapy-naive patients treated 
      with attenuated doses of ketoconazole (200-300 mg three times daily) had PSA 
      response rate (>50% decline) of 21-62%. We hypothesized that low-dose 
      ketoconazole would likewise possess efficacy and tolerability in the CRPC 
      post-chemotherapy state. METHODS: Men with CRPC and performance status 0-3, 
      adequate organ function and who had received prior docetaxel were treated with 
      low-dose ketoconazole (200 mg orally three times daily) and hydrocortisone (20 mg 
      PO qAM and 10 mg PO qPM) until disease progression. Primary endpoint was PSA 
      response rate (>50% reduction from baseline) where a rate of 25% was to be 
      considered promising for further study (versus a null rate of <5%); 25 patients 
      were required. Secondary endpoints included PSA response >30% from baseline, 
      progression-free survival (PFS), duration of stable disease and evaluation of 
      adverse events (AEs). RESULTS: Thirty patients were accrued with median age of 72 
      years (range 55-86) and median pre-treatment PSA of 73 ng ml(-1) (range 
      7-11,420). Twenty-nine patients were evaluable for response and toxicity. PSA 
      response (>50% reduction) was seen in 48% of patients; PSA response (>30% 
      reduction) was seen in 59%. Median PFS was 138 days; median duration of stable 
      disease was 123 days. Twelve patients experienced grade 3 or 4 AEs. Of the 17 
      grade 3 AEs, only 3 were attributed to treatment. None of the two grade 4 AEs 
      were considered related to treatment. CONCLUSIONS: In docetaxel pre-treated CRPC 
      patients, low-dose ketoconazole and hydrocortisone is a well-tolerated, 
      relatively inexpensive and clinically active treatment option. PSA response to 
      low-dose ketoconazole appears historically comparable to that of abiraterone in 
      this patient context. A prospective, randomized study of available 
      post-chemotherapy options is warranted to assess comparative efficacy.
FAU - Lo, E N
AU  - Lo EN
AD  - Department of Internal Medicine, University of California Davis Comprehensive 
      Cancer Center, Sacramento, CA, USA.
FAU - Beckett, L A
AU  - Beckett LA
AD  - Department of Internal Medicine, University of California Davis Comprehensive 
      Cancer Center, Sacramento, CA, USA.
FAU - Pan, C X
AU  - Pan CX
AD  - 1] Department of Internal Medicine, University of California Davis Comprehensive 
      Cancer Center, Sacramento, CA, USA [2] VA Northern California Health Care System, 
      Mather, CA, USA.
FAU - Robles, D
AU  - Robles D
AD  - Department of Internal Medicine, University of California Davis Comprehensive 
      Cancer Center, Sacramento, CA, USA.
FAU - Suga, J M
AU  - Suga JM
AD  - Kaiser-Permanente Medical Center, Vallejo, CA, USA.
FAU - Sands, J M
AU  - Sands JM
AD  - Lahey Hospital and Medical Center, Burlington, MA, USA.
FAU - Lara, P N Jr
AU  - Lara PN Jr
AD  - Department of Internal Medicine, University of California Davis Comprehensive 
      Cancer Center, Sacramento, CA, USA.
LA  - eng
GR  - I01 BX001784/BX/BLRD VA/United States
GR  - P30 CA093373/CA/NCI NIH HHS/United States
GR  - P30CA093373-06/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20150210
PL  - England
TA  - Prostate Cancer Prostatic Dis
JT  - Prostate cancer and prostatic diseases
JID - 9815755
RN  - 0 (Taxoids)
RN  - 15H5577CQD (Docetaxel)
RN  - EC 3.4.21.77 (Prostate-Specific Antigen)
RN  - R9400W927I (Ketoconazole)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage
MH  - Disease Progression
MH  - Disease-Free Survival
MH  - Docetaxel
MH  - Humans
MH  - Hydrocortisone/*administration & dosage
MH  - Ketoconazole/*administration & dosage
MH  - Male
MH  - Middle Aged
MH  - Prostate-Specific Antigen/blood
MH  - Prostatic Neoplasms, Castration-Resistant/blood/*drug therapy/pathology
MH  - Taxoids/*administration & dosage
MH  - Treatment Outcome
PMC - PMC4430382
MID - NIHMS651007
EDAT- 2015/02/11 06:00
MHDA- 2016/04/22 06:00
PMCR- 2015/12/01
CRDT- 2015/02/11 06:00
PHST- 2014/09/09 00:00 [received]
PHST- 2014/12/15 00:00 [revised]
PHST- 2014/12/21 00:00 [accepted]
PHST- 2015/02/11 06:00 [entrez]
PHST- 2015/02/11 06:00 [pubmed]
PHST- 2016/04/22 06:00 [medline]
PHST- 2015/12/01 00:00 [pmc-release]
AID - pcan20152 [pii]
AID - 10.1038/pcan.2015.2 [doi]
PST - ppublish
SO  - Prostate Cancer Prostatic Dis. 2015 Jun;18(2):144-8. doi: 10.1038/pcan.2015.2. 
      Epub 2015 Feb 10.