Sulforaphane treatment in men with recurrent prostate cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5017-5017 ◽  
Author(s):  
Joshi J. Alumkal ◽  
Rachel Slottke ◽  
Motomi Mori ◽  
Jacob Schwartzman ◽  
Julie Nicole Graff ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Doubling Time ◽  
Mononuclear Cells ◽  
Prostate Cancer Risk ◽  
Multiple Tumor ◽  
Psa Doubling Time ◽  
Psa Response ◽  
Psa Recurrence ◽  
Time Changes ◽  
Grade One

5017 Background: Diets high in cruciferous vegetables are strongly associated with lower prostate cancer risk. Sulforaphane is a constituent of these foods postulated to harbor the anti-neoplastic activity based on pre-clinical evidence in multiple tumor models. Our own work demonstrates that sulforaphane inhibits HDAC function and suppresses AR signaling in prostate cancer cells (Gibbs, et al PNAS 2009). However, the anti-tumor efficacy and safety of sulforaphane in men with prostate cancer was unknown. Methods: In this single arm study, we treated patients with biochemical (PSA)-recurrence of prostate cancer with 200 µmol of sulforaphane extracts for up to 20 weeks. The primary endpoint was PSA response rate (>50% decline in PSA). Other efficacy endpoints included: maximal PSA decline and percent change in PSA from baseline to end of study. We also analyzed PSA doubling time changes using a mixed effects model. Genotyping for GSTM1 that contributes to sulforaphane metabolism, sulforaphane pharmacokinetics (PK), and pharmacodynamic (PD) measurements of HDAC inhibition in mononuclear cells (MCs) were also performed. Results: Twenty patients were enrolled, and 16/20 (80%) completed the pre-planned 20 weeks of treatment. One patient experienced a PSA decline >50%. Thirty-five percent of patients had lesser PSA declines (3% to 20%), and 15% of patients had a final PSA lower than baseline. There was a significant reduction in PSA doubling time (6 months pre-study vs. 9.4 months on-study, p=.013). Of note, testosterone levels remained non-castrate in all subjects. PK analysis demonstrated that GSTM1 null genotype correlated with longer sulforaphane T1/2 (half-life) (2.6 hours for GSTM1 null vs. 2.1 hours for GSTM1 intact, p=0.04). Sulforaphane treatment also increased histone acetylation in PD assays in MCs. Finally, no grade three adverse events were seen, and only one patient discontinued study treatment for toxicity (grade one GI discomfort). Conclusions: Treatment with 200 µmol per day of sulforaphane is feasible, safe, and inhibits HDAC function. This combined with the preliminary observation of PSA modulation, which may indicate biologic activity, provides the basis for dose escalation studies of sulforaphane in men with prostate cancer. Clinical trial information: NCT01228084.

Public health impact of PSA doubling time after radical prostatectomy on prostate cancer specific and overall survival

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4568-4568
Author(s):  
S. J. Freedland ◽  
E. B. Humphreys ◽  
L. A. Mangold ◽  
M. Eisenberger ◽  
D. J. George ◽  
...  
Keyword(s):  
Public Health ◽  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Doubling Time ◽  
Health Concern ◽  
Small Subset ◽  
Risk Of Death ◽  
Psa Doubling Time ◽  
Increased Risk ◽  
Psa Recurrence

4568 Background: Among patients treated with radical prostatectomy (RP) with a PSA recurrence, we previously found men with a PSA doubling time (PSADT) <3 months were at increased risk of prostate cancer death, though these men constituted a small subset of patients. We sought to determine the actual and predicted number of prostate cancer deaths stratified by PSADT. Methods: We retrospectively studied 379 men treated with RP between 1982 and 2000 with a PSA recurrence. We calculated the actual and 15-year actuarial number of prostate cancer deaths in each of the following PSADT categories: <3, 3.0–8.9, 9.0–14.9, and ≥15.0 months. Results: Median follow-up after PSA recurrence was 7 years. During this time, there were 76 prostate cancer deaths; the majority (51%) were among men with a PSADT of 3.0–8.9 months. Though men with a PSADT <3 months were at the greatest risk of death, this group accounted for only 20% (n=15) of all prostate cancer deaths. Using actuarial 15-year estimates of prostate cancer specific survival, 50% of all prostate cancer deaths were among men with a PSADT of 3.0–8.9 months while men with a PSADT <3 months accounted for only 13% of prostate cancer deaths. Using actuarial 15-year estimates of all-cause and prostate cancer specific mortality, among men with a PSADT <15 months, prostate cancer was estimated to be the cause of death in 94% (145/155). Only among men with a PSADT >15 months was the risk of competing causes of mortality high enough such that the majority of deaths were not attributed to prostate cancer. Conclusions: Among a select cohort of men treated with RP who experienced a PSA recurrence, prostate cancer was estimated to account for 75% of all deaths. Though men with a PSADT <3 months were at the greatest risk, the majority of deaths occurred among men with a PSADT of 3.0–8.9 months. Efforts to reduce prostate cancer mortality should focus on men with intermediate PSADT times (3.0–15.0 months) as they represent the greatest public health concern among men with PSA recurrence following RP. [Table: see text] No significant financial relationships to disclose.

scholarly journals Phase II trial of acai juice product in biochemically recurrent prostate cancer.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 230-230 ◽  
Author(s):  
Elizabeth Riley Kessler ◽  
Lih-Jen Su ◽  
Xiaoping Yang ◽  
Xian Lu ◽  
Diana Morales ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Doubling Time ◽  
Recurrent Prostate Cancer ◽  
Psa Doubling Time ◽  
Psa Response ◽  
Psa Velocity ◽  
The One ◽  
Baseline Psa

230 Background: There are conflicting data as to the benefit of treating patients with biochemically recurrent prostate cancer (PCa). Plant derivatives, called “nutraceuticals” such as grape seed extract or milk thistle, have been studied as therapies for PCa based on their purported anti-inflammatory and anti-oxidant properties and low toxicities. Acai is a fruit rich in bioflavinoids shown to induce apoptosis in preclinical studies of PCa, leukemia and esophageal cancer. Anecdotal experience of two patients with falling prostate specific antigen (PSA) values while consuming acai juice prompted us to evaluate its efficacy in a clinical trial. Methods: This was a phase II Simon two-stage open-label single-arm single-institution study of the efficacy of Acai Juice Product in asymptomatic PCa patients with a rising PSA. Eligibility included lack of current hormone therapy, hormone sensitivity, and a PSA doubling time of >4 weeks. Patients consumed 2 oz of Acai Juice Product twice daily for 30 weeks, with a primary endpoint of PSA response. Secondary endpoints included PSA doubling time, PSA velocity, and duration of PSA response. Progression was defined as a rise of 25% from baseline PSA with absolute rise of 2ng/dL. Results: 21 patients were enrolled in the first stage of the trial. Median baseline PSA was 2.74 (range 0.38-36.88). Eighteen patients have completed therapy with 1 PSA response. In the one responder, the patient entered with a doubling time of 4 months and a PSA of 12.57, which was 2.15 at 36 weeks suggesting a prolonged and continued response. PSA either decreased or doubling time prolonged from baseline in 18 patients. PSA velocity was a negative rate of change per month in 4 patients. Conclusions: Acai juice did not produce enough PSA responses in this patient population to proceed beyond the first stage of this trial. However, PSA doubling time did slow in 85.7% of patients, and the one observed PSA response was sustained over at least 36 weeks at the time of data cutoff. Thus, we will analyze potential cellular signals through an M30 Apotosense ELISA assay and Human Cytokine 10-plex panel on patient samples with data available for presentation at the meeting. Clinical trial information: NCT01521949.

scholarly journals The Use of PSA Doubling Time to Predict Prognosis and the Use of PSA Response to Assess the Success for Prostate Cancer Patients Undergoing Docetaxel Chemotherapy

2016 ◽  
Vol 07 (08) ◽  
pp. 593-599
Author(s):  
Sarp K. Keskin ◽  
Asif Yildirim ◽  
Cengiz Canakci ◽  
Ismail Ulus ◽  
Ramazan Gokhan Atis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Doubling Time ◽  
Psa Doubling Time ◽  
Psa Response ◽  
Docetaxel Chemotherapy

A phase II trial of thalidomide, bevacizumab, and docetaxel in patients (pts) with metastatic androgen-independent prostate cancer (AIPC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5114-5114 ◽  
Author(s):  
Y. M. Ning ◽  
P. Arlen ◽  
J. Gulley ◽  
L. Latham ◽  
E. Jones ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Doubling Time ◽  
Vital Role ◽  
Colon Perforation ◽  
Antiangiogenic Agents ◽  
Psa Doubling Time ◽  
Measurable Disease ◽  
Psa Response ◽  
Grade 3

5114 Background: Angiogenesis plays a vital role in the progression of prostate cancer. Antiangiogenic agents thalidomide (T) and bevacizumab (Bv) may enhance docetaxel (Doc) activity in metastatic AIPC. However, T and Bv have different antiangiogenic mechanisms. Since tumor angiogenesis is a complex interplay of multiple angiogenic factors, we reasoned that combination of mechanistically different antiangiogenic agents T and Bv with Doc might be associated with an adequately high and durable PSA response to merit further study. Methods: Pts are required to have progressive metastatic AIPC and no prior chemotherapy for AIPC. Treatment consists of Doc 75 mg/m2 plus Bv 15 mg/kg day 1, q 21 days as a cycle (C), plus T 200 mg qhs and prednisone 10 mg qd. Enoxaparin is used for thrombosis prevention and pegfilgrastim initiated after detection of grade ≥3 neutropenia. PSA is assayed q C and staging studies are done at C 0, C 2, & then q 3 Cs. Results: 39 pts were enrolled, median age 66 [54–79], Gleason score 8 [74% Gs 10∼8, 26% Gs 7∼6], on-study PSA 92 ng/ml [5.9–4399] and pre-study PSA doubling time 1.6 months [0.3–18.2, 87 % <3 months]. Median treatment Cs is 14 [1- 28]. 34 pts (87%) had PSA declines of ≥50%, with median ≥50% PSA-duration 12 Cs [0∼28]. 3 pts have PSA declines around 40% and 2 stable. 26 pts (67%) had >80% PSA declines. 17 pts with measurable disease were evaluable: 1 CR, 9 PR, & 7 SD, with 59% ORR. Significant toxicities: febrile neutropenia (5/39), syncope (4/39), colon perforation or fistula (2/39), grade 3 bleeding (2/39), thrombosis (2/39). Conclusions: This trial is the first study to combine antiangiogenic agents of different mechanisms with Doc in metastatic AIPC. Most of the accrued patients have unfavorable characteristics as evidenced by a high Gleason score and a short PSA doubling time. However, the combination of T and Bv with Doc appears to result in both a high durable PSA decline rate (87%) and a high response in measurable disease (59%) with acceptable toxicities. No significant financial relationships to disclose.

665: Baseline PSA and PSA Doubling Time Predict the Risk of Objective Progression and Death in Patients with T0-4 N0-2 M0 Prostate Cancer on Watchful Waiting

2006 ◽  
Vol 175 (4S) ◽  
pp. 215-215 ◽  
Author(s):  
Urs E. Studer ◽  
Laurence Collette ◽  
Peter Whelan ◽  
Walter Albrecht ◽  
Jacques Casselman ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Doubling Time ◽  
Watchful Waiting ◽  
Psa Doubling Time ◽  
Baseline Psa

scholarly journals Resolution of the Expert Council on the New Approach to Drug Therapy for Non-Metastatic Castration-Resistant Prostate Cancer

2021 ◽  
Vol 59 (1) ◽  
pp. 8-11
Author(s):  
Dilyara Kaidarova ◽  
Oxana Shatkovskaya ◽  
Zaure Dushimova ◽  
Bakytzhan Ongarbayev
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Treatment Efficacy ◽  
Doubling Time ◽  
Distant Metastases ◽  
Diagnostic Methods ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Doubling Time

Relevance: Prostate cancer (PC) is one of the most common malignant neoplasms in the male population. The widespread introduction of modern diagnostic methods and the determination of prostate-specific antigen (PSA) levels have increased the number of detected cases of localized and locally advanced PC forms. However, in some patients treated with radical methods and long-term androgen deprivation therapy (ADT), the disease continues to progress in the form of an increase in PSA levels with castration testosterone values and with no distant metastases. Such a course of the disease is referred to as non-metastatic castration-resistant prostate cancer (nmCRPC). Purpose: The article reports the results of a meeting of the Expert Council arranged by the Kazakh Research Institute of Oncology and Radiology on December 25, 2020, on non-metastatic castration-resistant prostate cancer diagnostics and treatment. Results: Large clinical studies highlight the critical importance of controlling the PSA doubling time as the main prognostic factor for an unfavorable outcome to increase patient survival and prevent the development of distant metastases. Based on the results of large randomized studies, experts recommended using new-generation androgen receptor antagonists in combination with ongoing ADT to improve the clinical outcomes in nmCRPC patients at high risk of metastatic progression. The Expert Council was presented with the data of a registration clinical study on darolutamide efficacy and safety. The advantages of introducing this drug into clinical practice to expand the choice of therapeutic options were identified. Personalized adjustment of a treatment regimen will increase the treatment efficacy and ensure higher survival in this category of patients. Conclusion: Increasing survival as the main objective in treating nmCRPC patients requires improved diagnostics through regular controlling of testosterone and PSA levels, calculation of PSA doubling time, and the use of radiological diagnostic methods to rule out distant metastases. The choice of therapy in patients at high risk of metastasis shall consider the patient’s status and the treatment efficacy and safety balance.

scholarly journals Safety and Immunological Efficacy of a DNA Vaccine Encoding Prostatic Acid Phosphatase in Patients With Stage D0 Prostate Cancer

2009 ◽  
Vol 27 (25) ◽  
pp. 4047-4054 ◽  
Author(s):  
Douglas G. McNeel ◽  
Edward J. Dunphy ◽  
James G. Davies ◽  
Thomas P. Frye ◽  
Laura E. Johnson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cells ◽  
Acid Phosphatase ◽  
T Cell ◽  
Dna Vaccine ◽  
Cd8 T Cells ◽  
Doubling Time ◽  
Prostatic Acid Phosphatase ◽  
T Cell Response ◽  
Psa Doubling Time

Purpose Prostatic acid phosphatase (PAP) is a prostate tumor antigen. We have previously demonstrated that a DNA vaccine encoding PAP can elicit antigen-specific CD8+ T cells in rodents. We report here the results of a phase I/IIa trial conducted with a DNA vaccine encoding human PAP in patients with stage D0 prostate cancer. Patients and Methods Twenty-two patients were treated in a dose-escalation trial with 100 μg, 500 μg, or 1,500 μg plasmid DNA, coadministered intradermally with 200 μg granulocyte-macrophage colony-stimulating factor as a vaccine adjuvant, six times at 14-day intervals. All patients were observed for 1 year after treatment. Results No significant adverse events were observed. Three (14%) of 22 patients developed PAP-specific IFNγ-secreting CD8+ T-cells immediately after the treatment course, as determined by enzyme-linked immunospot. Nine (41%) of 22 patients developed PAP-specific CD4+ and/or CD8+ T-cell proliferation. Antibody responses to PAP were not detected. Overall, the prostate-specific antigen (PSA) doubling time was observed to increase from a median 6.5 months pretreatment to 8.5 months on-treatment (P = .033), and 9.3 months in the 1-year post-treatment period (P = .054). Conclusion The demonstration that a DNA vaccine encoding PAP is safe, elicits an antigen-specific T-cell response, and may be associated with an increased PSA doubling time suggests that a multi-institutional phase II trial designed to evaluate clinical efficacy is warranted.

Utility of PSA doubling time in follow-up of untreated patients with localized prostate cancer

Urology ◽  
2002 ◽  
Vol 59 (5) ◽  
pp. 652-656 ◽  
Author(s):  
Andrew J Stephenson ◽  
Armen G Aprikian ◽  
Luis Souhami ◽  
Hassan Behlouli ◽  
Avrum I Jacobson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Doubling Time ◽  
Localized Prostate Cancer ◽  
Psa Doubling Time
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