Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer: A report from the ASCENT Investigators
Document Type
Article
Department
Haematology and Oncology, East Africa
Abstract
Purpose: To compare the safety and activity of DN-101, a new high-dose oral formulation of calcitriol designed for cancer therapy, and docetaxel with placebo and docetaxel.
Patients and Methods: Patients with progressive metastatic androgen-independent prostate cancer and adequate organ function received weekly docetaxel 36 mg/m2 intravenously for 3 weeks of a 4-week cycle combined with either 45 μg DN-101 or placebo taken orally 1 day before docetaxel. The primary end point was prostate-specific antigen (PSA) response within 6 months of enrollment, defined as a 50% reduction confirmed at least 4 weeks later.
Results: Two hundred fifty patients were randomly assigned. Baseline characteristics were similar in both arms. Within 6 months, PSA responses were seen in 58% in DN-101 patients and 49% in placebo patients (P = .16). Overall, PSA response rates were 63% (DN-101) and 52% (placebo), P = .07. Patients in the DN-101 group had a hazard ratio for death of 0.67 (P = .04) in a multivariate analysis that included baseline hemoglobin and performance status. Median survival has not been reached for the DN-101 arm and is estimated to be 24.5 months using the hazard ratio, compared with 16.4 months for placebo. Grade 3/4 adverse events occurred in 58% of DN-101 patients and in 70% of placebo-treated patients (P = .07). Most common grade 3/4 toxicities for DN-101 versus placebo were neutropenia (10% v 8%), fatigue (8% v 16%), infection (8% v 13%), and hyperglycemia (6% v 12%).
Conclusion: This study suggests that DN-101 treatment was associated with improved survival, but this will require confirmation because survival was not a primary end point. The addition of weekly DN-101 did not increase the toxicity of weekly docetaxel.
Publication (Name of Journal)
Journal of Clinical Oncology
DOI
https://doi.org/10.1200/JCO.2006.06.8197
Recommended Citation
M. Beer, T.,
W. Ryan, C.,
M. Venner, P.,
Petrylak, D.,
S. Chatta, G.,
Ruether, J.,
Redfern, C.,
Fehrenbacher, L.,
Saleh, M.,
Waterhouse, D.
(2007). Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer: A report from the ASCENT Investigators. Journal of Clinical Oncology, 25(6), 1-6.
Available at:
https://ecommons.aku.edu/eastafrica_fhs_mc_haematol_oncol/21
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Comments
This work was published before the author joined Aga Khan University.