TY - JOUR
T1 - ASCENT
T2 - The androgen-independent prostate cancer study of calcitriol enhancing taxotere
AU - Beer, Tomasz M.
PY - 2005/9
Y1 - 2005/9
N2 - ASCENT, the Androgen-Independent Prostate Cancer (AIPC) Study of Calcitriol Enhancing Taxotere, is a double-blind, placebo-controlled randomized clinical trial designed to determine if DN-101, a high-dose oral formulation of calcitriol designed for cancer therapy, significantly increases the proportion of patients who have >50% reduction in serum prostate-specific antigen (PSA) levels in response to docetaxel. The secondary goals of ASCENT are to evaluate the effect of DN-101 combined with docetaxel on PSA progression-free survival, tumour response rate in measurable disease, tumour progression-free survival, skeletal morbidity-free survival, clinical progression-free survival, and overall survival, and to examine the safety and tolerability of DN-101 combined with docetaxel. ASCENT builds on phase I work showing that weekly dosing allows substantial dose-escalation of calcitriol, the natural ligand for the vitamin D receptor, and on phase II work that suggested that adding weekly high-dose 'pulse' calcitriol may enhance the activity of weekly docetaxel in patients with AIPC. The preclinical rationale for calcitriol and its combination with docetaxel for prostate cancer therapy is reviewed, as are the key clinical trials that led to the development of ASCENT. The ASCENT design and its strengths and limitations are presented.
AB - ASCENT, the Androgen-Independent Prostate Cancer (AIPC) Study of Calcitriol Enhancing Taxotere, is a double-blind, placebo-controlled randomized clinical trial designed to determine if DN-101, a high-dose oral formulation of calcitriol designed for cancer therapy, significantly increases the proportion of patients who have >50% reduction in serum prostate-specific antigen (PSA) levels in response to docetaxel. The secondary goals of ASCENT are to evaluate the effect of DN-101 combined with docetaxel on PSA progression-free survival, tumour response rate in measurable disease, tumour progression-free survival, skeletal morbidity-free survival, clinical progression-free survival, and overall survival, and to examine the safety and tolerability of DN-101 combined with docetaxel. ASCENT builds on phase I work showing that weekly dosing allows substantial dose-escalation of calcitriol, the natural ligand for the vitamin D receptor, and on phase II work that suggested that adding weekly high-dose 'pulse' calcitriol may enhance the activity of weekly docetaxel in patients with AIPC. The preclinical rationale for calcitriol and its combination with docetaxel for prostate cancer therapy is reviewed, as are the key clinical trials that led to the development of ASCENT. The ASCENT design and its strengths and limitations are presented.
KW - Calcitriol
KW - Prostate cancer
KW - Vitamin D
UR - http://www.scopus.com/inward/record.url?scp=24044457933&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=24044457933&partnerID=8YFLogxK
U2 - 10.1111/j.1464-410X.2005.05675.x
DO - 10.1111/j.1464-410X.2005.05675.x
M3 - Review article
C2 - 16104901
AN - SCOPUS:24044457933
SN - 1464-4096
VL - 96
SP - 508
EP - 513
JO - BJU international
JF - BJU international
IS - 4
ER -