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.

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

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13037-13037 ◽  
Author(s):  
Y. M. Ning ◽  
P. M. Arlen ◽  
J. Gulley ◽  
L. Latham ◽  
A. Retter ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Vital Role ◽  
Circulating Endothelial Cells ◽  
Colon Perforation ◽  
Antiangiogenic Agents ◽  
Phase Ii Trials ◽  
Durable Response ◽  
Pre Treatment ◽  
Novel Strategy

13037 Background: Angiogenesis plays a vital role in progression of prostate cancer. Antiangiogenic agents’ thalidomide (Td) and bevacizumab (Bv) have been shown in Phase II trials to enhance docetaxel (Doc) activity in metastatic AIPC. Td plus Doc also improved median overall survival as compared to Doc alone. Td and Bv have different antiangiogenic mechanisms. Td appears to affect bFGF, alter circulating endothelial cells and inhibit TNF expression; yet Td does not affect the target of Bv (VEGF). Since tumor angiogenesis is a complex interplay of multiple angiogenic factors, we reasoned that combination of mechanistically different antiangiogenic agents Td and Bv with Doc might be associated with an adequately high and durable PSA response to merit further study. Methods: Pts have progressive, metastatic AIPC, with no prior chemotherapy for AIPC, or prior Td or Bv. Treatment consists of Doc 75 mg/m2 plus Bv 15 mg/kg day 1, q 21 days as a cycle (C), plus Td 200 mg qhs and prednisone10 mg qd. Enoxaparin 1 mg/kg/d sq is used for thrombosis prevention. PSA is assayed q C and radiographic studies are performed at C 0, C 2, & then q 3 Cs. Results: To date, 22 of planned 60 pts have been enrolled, median age 65 [54–79], Gleason score 8 [Gs 6∼7: 32%, Gs 8∼10: 68%], on-study PSA 111 ng/ml [7.7–4399], & pre-treatment PSA doubling time 1.7 months [0.8–18.2]. I) All 22 pts are actively on trial without progression, with median treatment 6 Cs [1–12]. II) 20 pts treated ≥ 2 Cs, 17 (85%) had PSA declines of >50%, 2 declines of >20%, and 1 stable; median duration of >50% PSA decline is 5 Cs [0∼11]. III) 14 pts (of the 20) treated ≥ 5 Cs, 13 (93%) had >50% PSA declines; 6 of them also had measurable disease: 1 CR, 2 PR, & 3 SD (50% RR). IV) Significant toxicities include grade 4 neutropenia (11/22), grade 3 febrile neutropenia (3/22), syncope (2/22), & colon perforation (1/22). No thrombosis was seen. Conclusions: This trial tests a novel strategy of improving conventional treatment of metastatic AIPC. Our data show that the combination of two mechanistically different antiangiogenic agents Td and Bv with Doc does result in a high durable response in PSA (85∼93%) with acceptable toxicities, suggesting that further studies with the combination are warranted. Accrual is continuing. No significant financial relationships to disclose.

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.

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.

Ultrasensitive PSA nadir on testosterone inactivating pharmaceuticals accurately predicts early prostate cancer progression

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14531-14531 ◽  
Author(s):  
M. C. Scholz ◽  
R. Lam ◽  
B. Guess ◽  
S. Strum ◽  
H. Johnson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Gleason Score ◽  
Doubling Time ◽  
Median Response ◽  
Cox Regression Analysis ◽  
Psa Doubling Time ◽  
Tip Resistance ◽  
Early Progression ◽  
Psa Nadir

14531 Background: Prostate cancer has a variable natural history. Researchers and clinicians sorely need a marker identifying men destined for early progression to bone metastasis (EPBM). Prostate cancer is uniquely sensitive to testosterone inactivating pharmaceuticals (TIP) especially when TIP is initiated prior to the onset of bone metastasis. Moul 1 reported 10 year median response in men with a rising PSA after surgery. With such effective therapy, predicting EPBM requires a marker signaling TIP resistance. Elevated PSA nadir is a likely candidate. Methods: Retrospective chart review of 159 men with prostate cancer started on TIP before 1/1/00 with negative bone scan and PSA < 100. The predictive value of Gleason score, initial PSA, PSA doubling-time (DT), clinical stage, and ultra-sensitive PSA nadir were evaluated for their ability to predict EPBM within 72 months of starting TIP. TIP consisted of an antiandrogen and LHRH agonist. Results: Median follow was 9.25 years. Median values for patient age, initial PSA, PSA nadir, and PSA doubling time were 65.9, 9.6, 0.03 and 10 months respectively. Sixty men were staged as: T1c-T3b, 46 PSA relapse, and 53 stages T3c, D0 or D1. Thirty-five men developed EPBM. PSA nadir was the most accurate predictor of EPBM (see Table). Only 8% of men with PSA nadir ≤0.05 had EPBM compared to 78% with high nadirs. Cox regression analysis indicated that PSA nadir, Gleason score, and PSA doubling time < 12 months independently predicted EPBM. Median and maximum time to PSA nadir were 4 and 8 months respectively. Conclusions: Ultra-sensitive PSA nadir is a more accurate indicator of early progression to bone metastasis (90%) than Gleason score (75%) as well as being more sensitive and specific (72% vs. 37%) and (95% vs. 86%) respectively. This prognostic information provided by PSA nadir is obtainable within the first 8 months of starting TIP in virtually all patients (97%). 1. Moul JW et al. J Urol 2005, 171: 1141–7. [Table: see text] No significant financial relationships to disclose.

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

Predictors of outcome using salvage androgen deprivation therapy after radical prostatectomy.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 74-74
Author(s):  
M. K. Tollefson ◽  
E. J. Bergstralh ◽  
L. J. Rangel ◽  
R. J. Karnes
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Treatment Failure ◽  
Disease Progression ◽  
Androgen Deprivation Therapy ◽  
Gleason Score ◽  
Doubling Time ◽  
Systemic Disease ◽  
Psa Doubling Time ◽  
Salvage Androgen Deprivation Therapy

74 Background: Nearly all men that experience recurrence of prostate cancer after radical prostatectomy are placed on salvage androgen deprivation therapy (sADT) in an attempt to control the disease. Yet, little is known regarding the efficacy of the treatment, the therapeutic duration or the predictors of treatment failure. Therefore, we examined our experience with sADT after radical prostatectomy in a cohort of patients with no evidence of systemic disease. Methods: We identified 1,373 patients that were treated with sADT after radical prostatectomy prior to the development of systemic disease. Clinical and pathologic variables predicting systemic progression and cancer death were evaluated using the Kaplan-Meier method and compared using the log rank test. Multivariate Cox proportional hazard regression models were used to analyze the impact of these variables on disease progression and survival. Results: Patients were treated with sADT at a median of 4.2 years after surgery. The median PSA at initiation of sADT was 1.6 ng/mL. The majority (1,234, 90%) of patients had a calculable PSA doubling time prior to the initiation of sADT. 275 patients (20.0%) experienced systemic progression at a median of 3.1 years after the start of sADT. 175 patients (12.7%) died of prostate cancer at a median of 4.7 years after the start of sADT. Factors that predicted disease progression after sADT on multivariate analysis included either neoadjuvant or adjuvant ADT (HR - 2.0, p<0.0001), increasing pathologic Gleason Score (HR - 1.18, p=0.009), increasing pathologic stage (HR - 1.3, p<0.0001), PSA at start of sADT (HR - 1.3, p<0.0001) and PSA doubling time (1.65, p<0.0001). Conclusions: Most men treated with sADT after radical prostatectomy prior to the development of systemic progression experience a lengthy disease-free interval. Multivariate predictors of treatment failure include prior adjuvant or neoadjuvant ADT, pathologic Gleason Score, pathologic stage, PSA level at initiation of sADT and PSA doubling time before sADT. No significant financial relationships to disclose.

1423: The Impact of Gleason Score on the Predictive Value of PSA Doubling Time

2007 ◽  
Vol 177 (4S) ◽  
pp. 469-470 ◽  
Author(s):  
Stephen A. Boorjian ◽  
Sameer A. Siddiqui ◽  
Brant A. Inman ◽  
Jeffrey M. Slezak ◽  
R. Jeffrey Karnes ◽  
...  
Keyword(s):  
Gleason Score ◽  
Predictive Value ◽  
Doubling Time ◽  
Psa Doubling Time ◽  
The Impact

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.

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