ASCENT: the androgen-independent prostate cancer study of calcitriol enhancing taxotere.
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.
Beer
Tomasz M
TM
Department of Medicine, Division of Hematology & Medical Oncology, Oregon Health & Science University, Portland 97239, USA. beert@ohsu.edu
D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D002117:Calcitriol / Q000627:therapeutic use*; D002170:Canada; D018572:Disease-Free Survival; D000077143:Docetaxel; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate; D043823:Taxoids / Q000627:therapeutic use; D014481:United States
D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D010919:Placebos; D043823:Taxoids; D000077143:Docetaxel; D017430:Prostate-Specific Antigen; D002117:Calcitriol