PMID- 23830964
OWN - NLM
STAT- MEDLINE
DCOM- 20140718
LR  - 20220408
IS  - 1938-0682 (Electronic)
IS  - 1558-7673 (Linking)
VI  - 11
IP  - 4
DP  - 2013 Dec
TI  - A phase II trial of temsirolimus in men with castration-resistant metastatic 
      prostate cancer.
PG  - 397-406
LID - S1558-7673(13)00138-9 [pii]
LID - 10.1016/j.clgc.2013.05.007 [doi]
AB  - BACKGROUND: Phosphatase and tensin homologue (PTEN) loss is common in advanced 
      prostate cancer, leading to constitutive activation of the PI3 kinase pathway. 
      Temsirolimus blocks mammalian target of rapamycin (mTOR)/target of rapamycin 
      complex 1 (TORC1), a key signaling node in this pathway; its activity in men with 
      advanced castration-resistant metastatic prostate cancer (mCRPC) is unknown. 
      METHODS: We conducted a single-arm trial of weekly intravenous temsirolimus 
      administration in men with chemorefractory mCRPC who had >/= 5 circulating tumor 
      cells (CTCs) at baseline. The primary end point was the change in CTCs at 8 
      weeks; secondary end points were composite progression-free survival (PFS) 
      (excluding prostate-specific antigen [PSA]), PSA and radiographic response rates, 
      safety, and survival. At PSA/CTC progression, an anti-androgen could be added 
      while continuing temsirolimus. RESULTS: Eleven patients were accrued out of a 
      planned 20; the trial was stopped prematurely because of lack of 
      efficacy/feasibility. Median age was 61 years, with 55% African-Americans and 36% 
      Caucasian patients. Median baseline PSA level was 390 ng/dL, median baseline 
      number of CTCs was 14 cells; 50% of patients had pain, and 63% had undergone >/= 2 
      previous chemotherapy regimens. Median CTC decline was 48% and 3 patients 
      experienced decline in CTCs to < 5. However, 73% of men had a persistently 
      unfavorable number of CTCs (>/= 5) and only 1 patient had a >/= 30% PSA decline. 
      Median PFS was 1.9 months (95% confidence interval [CI], 0.9-3.1) and median 
      overall survival (OS) was 8.8 months (95% CI, 3.1-15.6). Toxicities included 
      grade 4 hypophosphatemia and central nervous system (CNS) hemorrhage, and 
      frequent grade 3 fatigue, anemia, stomatitis, hypokalemia, weakness, and 
      hyperglycemia. CONCLUSION: Temsirolimus lacked sufficient clinical activity in 
      men with mCRPC, despite transient CTC improvements in some men. Future studies 
      should focus on combination approaches or novel PI3K pathway inhibitors.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Armstrong, Andrew J
AU  - Armstrong AJ
AD  - Duke Cancer Institute and the Duke Prostate Center, Duke University, Durham NC; 
      Department of Medicine, Division of Medical Oncology, Duke University, Durham NC; 
      Department of Surgery, Division of Urology, Duke University, Durham NC; Duke 
      University Medical Center, Duke University, Durham NC. Electronic address: 
      andrew.armstrong@duke.edu.
FAU - Shen, Tong
AU  - Shen T
FAU - Halabi, Susan
AU  - Halabi S
FAU - Kemeny, Gabor
AU  - Kemeny G
FAU - Bitting, Rhonda L
AU  - Bitting RL
FAU - Kartcheske, Patricia
AU  - Kartcheske P
FAU - Embree, Elizabeth
AU  - Embree E
FAU - Morris, Karla
AU  - Morris K
FAU - Winters, Carolyn
AU  - Winters C
FAU - Jaffe, Tracy
AU  - Jaffe T
FAU - Fleming, Mark
AU  - Fleming M
FAU - George, Daniel J
AU  - George DJ
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20130703
PL  - United States
TA  - Clin Genitourin Cancer
JT  - Clinical genitourinary cancer
JID - 101260955
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 624KN6GM2T (temsirolimus)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.4.21.77 (Prostate-Specific Antigen)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Bone Neoplasms/secondary
MH  - Disease Progression
MH  - Disease-Free Survival
MH  - Humans
MH  - Male
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Middle Aged
MH  - Multiprotein Complexes/antagonists & inhibitors
MH  - Neoplastic Cells, Circulating
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Prostate-Specific Antigen/blood
MH  - Prostatic Neoplasms, Castration-Resistant/*drug therapy/mortality
MH  - Protein Kinase Inhibitors/*adverse effects/*therapeutic use
MH  - Sirolimus/adverse effects/*analogs & derivatives/therapeutic use
MH  - Survival
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors
MH  - Treatment Failure
OTO - NOTNLM
OT  - Castration-resistant
OT  - Circulating tumor cells
OT  - Epithelial-mesenchymal transition
OT  - Metastatic prostate cancer
OT  - N-cadherin
OT  - Prostate-specific antigen
OT  - Temsirolimus
OT  - mTOR
EDAT- 2013/07/09 06:00
MHDA- 2014/07/19 06:00
CRDT- 2013/07/09 06:00
PHST- 2013/01/22 00:00 [received]
PHST- 2013/05/14 00:00 [revised]
PHST- 2013/05/14 00:00 [accepted]
PHST- 2013/07/09 06:00 [entrez]
PHST- 2013/07/09 06:00 [pubmed]
PHST- 2014/07/19 06:00 [medline]
AID - S1558-7673(13)00138-9 [pii]
AID - 10.1016/j.clgc.2013.05.007 [doi]
PST - ppublish
SO  - Clin Genitourin Cancer. 2013 Dec;11(4):397-406. doi: 10.1016/j.clgc.2013.05.007. 
      Epub 2013 Jul 3.