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

Beer, Tomasz M.; Ryan, Christopher W.; Venner, Peter; Petrylak, Daniel P.; Chatta, Gurkamal S.; Ruether, J. Dean; Redfern, Charles H.; Fehrenbacher, Louis; Saleh, Mansoor N.; Waterhouse, David; Carducci, Michael A.; Vicario, Daniel; Dreicer, Robert; Higano, Celestia S.; Ahmann, Frederick R.; N., Kim; Henner, W. David; Arroyo, Alan M; Clow, Fong

doi:10.1200/jco.2006.06.8197

Cited by 297 publications

(169 citation statements)

References 25 publications

Supporting

Mentioning

159

Contrasting

Unclassified

Order By: Relevance

“…However, OS in the DN-101-treated group was improved significantly over the placebo group (P ¼ 0.04). 8 Similar findings were reported in the development of the immunotherapeutic agent APC8015 (Provenge). 9 In a double-blind phase II trial evaluating zibotentan (ZD4054), an endothelin A (ET A ) receptor-specific antagonist, pain-free or mildly symptomatic HRPC patients with bone metastases received once-daily zibotentan (15 or 10 mg/day) or placebo.…”

Section: Appraisal Of End Points In Phase II and Iii Trials In Castrasupporting

confidence: 72%

Measuring therapeutic efficacy in the changing paradigm of castrate-resistant prostate cancer

Mulders

Schalken

2009

Prostate Cancer Prostatic Dis

View full text Add to dashboard Cite

One of the current challenges in the evaluation of novel agents for the treatment of advanced prostate cancer is the identification of a surrogate end point for overall survival (OS). Prostatespecific antigen (PSA) levels have been used as a screening tool and a biomarker of response to both hormonal and cytotoxic agents. However, PSA levels do not seem to be a suitable surrogate end point for OS in trials of targeted agents for castrate-resistant prostate cancer (CRPC). These findings suggest the need for adopting measures of efficacy that more accurately reflect the mechanisms of action of these agents in phase II trials, in order to realize improvements in OS in the phase III setting. The Prostate Cancer Clinical Trials Working Group (PCWG2) have recently made recommendations for the design of future trials and advised that PSA levels should not be the sole criterion on which to base clinical decisions. Here, we appraise the end points that have been used in phase II and III trials in patients with CRPC, and highlight the need for the adoption of the PCWG2 guidelines, the recommendations of which include radiographic imaging, in addition to bone scintigraphy, and symptomatic or radiographic disease progression criteria.

show abstract

Section: Appraisal Of End Points In Phase II and Iii Trials In Castrasupporting

confidence: 72%

Measuring therapeutic efficacy in the changing paradigm of castrate-resistant prostate cancer

Mulders

Schalken

2009

Prostate Cancer Prostatic Dis

View full text Add to dashboard Cite

show abstract

“…Two of them were phase II studies with biochemical response as the primary endpoint [31,32] and the third used different schedules of docetaxel in the two arms [33]. Moreover, these clinical trials used either a synthetic vitD analog (Hectoral) or activated vitD (DN-101), which are not the standard replacement therapy for low vitD.…”

Section: Discussionmentioning

confidence: 99%

“…In a double-blinded, randomized phase II study (Androgen Independent Prostate Cancer Study of Calcitriol Enhancing Taxotere [ASCENT] trial) [32], the antineoplastic activity of the combination of DN-101, a high-dose oral formulation of calcitriol, and docetaxel was tested against docetaxel alone in 250 patients with advanced castrationresistant prostate cancer. The administration of DN-101 failed to be associated with a significantly higher PSA response rate-58% for DN-101 patients and 49% for placebo patients (p ϭ 0.16)-or a significantly longer skeletal morbidity-free survival duration (HR, 0.78; 95% CI, 0.57-1.074; p ϭ .13).…”

Section: Vitd Supplementationmentioning

confidence: 99%

Prognostic Role of Vitamin D Status and Efficacy of Vitamin D Supplementation in Cancer Patients: A Systematic Review

et al. 2011

View full text Add to dashboard Cite

show abstract

“…The ASCENT study combined docetaxel and 45 mg DN-101, a high-dose formulation of 1,25(OH) 2 D 3 that is specifically designed for cancer treatment, or placebo per week in PC patients and results were very promising. Addition of DN-101 to the regimen augments survival of the patients and decreases PSA (Beer et al 2007). These data suggest that DN-101 might enhance the antitumor effects of docetaxel.…”

Section: Clinical Trialsmentioning

confidence: 70%

Antineoplastic effects of 1,25(OH)2D3 and its analogs in breast, prostate and colorectal cancer

Leyssens¹,

Verlinden²,

Verstuyf³

2013

Endocrine-Related Cancer

View full text Add to dashboard Cite

The active form of vitamin D 3 , 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ), is mostly known for its importance in the maintenance of calcium and phosphate homeostasis. However, next to its classical effects on bone, kidney and intestine, 1,25(OH) 2 D 3 also exerts antineoplastic effects on various types of cancer. The use of 1,25(OH) 2 D 3 itself as treatment against neoplasia is hampered by its calcemic side effects. Therefore, 1,25(OH) 2 D 3 -derived analogs were developed that are characterized by lower calcemic side effects and stronger antineoplastic effects. This review mainly focuses on the role of 1,25(OH) 2 D 3 in breast, prostate and colorectal cancer (CRC) and the underlying signaling pathways. 1,25(OH) 2 D 3 and its analogs inhibit proliferation, angiogenesis, migration/invasion and induce differentiation and apoptosis in malignant cell lines. Moreover, prostaglandin synthesis and Wnt/b-catenin signaling are also influenced by 1,25(OH) 2 D 3 and its analogs. Human studies indicate an inverse association between serum 25(OH)D 3 values and the incidence of certain cancer types. Given the literature, it appears that the epidemiological link between vitamin D 3 and cancer is the strongest for CRC, however more intervention studies and randomized placebo-controlled trials are needed to unravel the beneficial dose of 1,25(OH) 2 D 3 and its analogs to induce antineoplastic effects.

show abstract

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

Abstract: 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.

Cited by 297 publications

References 25 publications

Measuring therapeutic efficacy in the changing paradigm of castrate-resistant prostate cancer

Measuring therapeutic efficacy in the changing paradigm of castrate-resistant prostate cancer

Prognostic Role of Vitamin D Status and Efficacy of Vitamin D Supplementation in Cancer Patients: A Systematic Review

Antineoplastic effects of 1,25(OH)2D3 and its analogs in breast, prostate and colorectal cancer

Contact Info

Product

Resources

About