Combined Analysis of Two Multicenter, Randomized, Placebo-Controlled Studies of Pamidronate Disodium for the Palliation of Bone Pain in Men With Metastatic Prostate Cancer

2003 ◽  
Vol 21 (23) ◽  
pp. 4277-4284 ◽  
Author(s):  
Eric J. Small ◽  
Matthew R. Smith ◽  
John J. Seaman ◽  
Stephanie Petrone ◽  
Mildred Ortu Kowalski
Keyword(s):  
Prostate Cancer ◽  
Bone Resorption ◽  
Bone Pain ◽  
Metastatic Prostate Cancer ◽  
Specific Antigen ◽  
Double Blind ◽  
Treatment Benefit ◽  
Bone Resorption Markers ◽  
Pamidronate Disodium ◽  
Analgesic Use

Purpose: Bone metastases occur in approximately 80% of patients with advanced prostate cancer. Pain is common in these patients. The purpose of this study was to evaluate the effect of an intravenous bisphosphonate, pamidronate disodium, on pain control in metastatic prostate cancer patients. Patients and Methods: Two multicenter, double-blind, randomized, placebo-controlled trials were conducted in patients with bone pain due to metastatic prostate cancer, with disease progression after first-line hormonal therapy. Intravenous pamidronate disodium (90 mg) or placebo was administered every 3 weeks for 27 weeks. Efficacy was measured via self-reported pain score (Brief Pain Inventory), analgesic use, the proportion of patients with a skeletal-related event (SRE; defined as pathologic fracture, radiation or surgery to bone, spinal cord compression, or hypercalcemia), and a pilot quantitative measurement of mobility. Laboratory evaluations included serum prostate-specific antigen, interleukin-6, bone alkaline phosphatase, and urinary bone resorption markers. Results: Results of the two trials were pooled. There were no sustained significant differences between the pamidronate and placebo groups in self-reported pain measurements, analgesic use, proportion of patients with an SRE, or mobility at week 9 or 27. Urinary bone resorption markers were suppressed in the pamidronate group compared with placebo. Conclusion: Pamidronate disodium failed to demonstrate a significant overall treatment benefit compared with placebo in palliation of bone pain or reduction of SREs. Evaluation of more potent bisphosphonates in patients with prostate cancer is warranted.

scholarly journals Prognostic role of docetaxel-induced suppression of free testosterone serum levels in metastatic prostate cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paula Kappler ◽  
Michael A. Morgan ◽  
Philipp Ivanyi ◽  
Stefan J. Brunotte ◽  
Arnold Ganser ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Cox Regression ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Serum Levels ◽  
Biologically Active ◽  
Free Form ◽  
Total Testosterone ◽  
The Impact

AbstractTo date, only few data concerning the biologically active, free form of testosterone (FT) are available in metastatic prostate cancer (mPC) and the impact of FT on disease, therapy and outcome is largely unknown. We retrospectively studied the effect of docetaxel on FT and total testosterone (TT) serum levels in 67 mPC patients monitored between April 2008 and November 2020. FT and TT levels were measured before and weekly during therapy. The primary endpoint was overall survival (OS). Secondary endpoints were prostate-specific antigen response and radiographic response (PSAR, RR), progression-free survival (PFS), FT/TT levels and safety. Median FT and TT serum levels were completely suppressed to below the detection limit during docetaxel treatment (FT: from 0.32 to < 0.18 pg/mL and TT: from 0.12 to < 0.05 ng/mL, respectively). Multivariate Cox regression analyses identified requirement of non-narcotics, PSAR, complete FT suppression and FT nadir values < 0.18 pg/mL as independent parameters for PFS. Prior androgen-receptor targeted therapy (ART), soft tissue metastasis and complete FT suppression were independent prognostic factors for OS. FT was not predictive for treatment outcome in mPC patients with a history of ART.

scholarly journals Characterization of a rat model of metastatic prostate cancer bone pain

2010 ◽  
pp. 213 ◽  
Author(s):  
Gurmit Singh ◽  
De Ciantis ◽  
Henry ◽  
Yashpal
Keyword(s):  
Prostate Cancer ◽  
Rat Model ◽  
Bone Pain ◽  
Metastatic Prostate Cancer

scholarly journals A phase 3 randomised study of enzalutamide plus leuprolide and enzalutamide monotherapy in high-risk non-metastatic hormone-sensitive prostate cancer with rising PSA after local therapy: EMBARK study design

BMJ Open ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. e046588
Author(s):  
Stephen J Freedland ◽  
Ugo De Giorgi ◽  
Martin Gleave ◽  
Brad Rosbrook ◽  
Qi Shen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Specific Antigen ◽  
Local Therapy ◽  
Standard Of Care ◽  
Open Label ◽  
Phase 3 ◽  
Double Blind ◽  
Randomised Study ◽  
Definitive Therapy

IntroductionLimited data from controlled clinical trials are available for men who experience biochemical recurrence after definitive therapy for prostate cancer. In the absence of overt metastases, patients with non-metastatic castration-sensitive prostate cancer (nmCSPC) often receive androgen deprivation therapy (ADT). There is no standard-of-care consensus on optimal ADT timing, although most men are treated prior to metastases, especially those with high-risk features (Gleason score 8–10 or prostate-specific antigen doubling time (PSADT) <9–12 months). Given data that ADT plus novel hormonal agents improve survival in men with metastatic CSPC, there is a desire to evaluate these agents earlier in the disease course. The main objective of EMBARK is the comparative assessment of enzalutamide plus leuprolide (luteinising hormone-releasing hormone agonist (LHRHa)) or enzalutamide monotherapy versus monotherapy LHRHa to improve metastasis-free survival (MFS) in patients with high-risk nmCSPC PSA recurrence after definitive therapy.Methods and analysisEMBARK is a randomised, phase 3 study of high-risk patients with nmCSPC, a PSADT of ≤9 months and a screening PSA of ≥2 ng/mL above the nadir after radiotherapy (RT) or ≥1 ng/mL after radical prostatectomy (RP) with or without postoperative RT. Men (n=1050) are randomised 1:1:1 to enzalutamide 160 mg/day plus LHRHa or placebo plus LHRHa (double-blind arms) or enzalutamide monotherapy (open-label arm). Treatment is suspended at week 37 if PSA concentrations are <0.2 ng/mL and reinstated if levels rise to ≥2.0 ng/mL with RP or ≥5.0 ng/mL without RP. Patients with PSA ≥0.2 ng/mL at week 37 continue until treatment discontinuation criteria are met. The primary endpoint is MFS comparing enzalutamide plus LHRHa versus placebo plus LHRHa.Ethics and disseminationThe study is conducted under the guiding principles of the World Medical Association Declaration of Helsinki. The results will be disseminated at research conferences and in peer-reviewed journals.Trial registration numberNCT02319837.

scholarly journals A novel immunocompetent model of metastatic prostate cancer‐induced bone pain

The Prostate ◽  
2020 ◽  
Vol 80 (10) ◽  
pp. 782-794
Author(s):  
Zhiqiang Liu ◽  
Stephen F. Murphy ◽  
Jian Huang ◽  
Lan Zhao ◽  
Christel C. Hall ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Pain ◽  
Metastatic Prostate Cancer

scholarly journals Disseminated Intravascular Coagulation as an Initial Manifestation of Metastatic Prostate Cancer Emergently Treated with Docetaxel-Based Chemotherapy

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Kavita Agrawal ◽  
Nirav Agrawal ◽  
Levin Miles
Keyword(s):  
Prostate Cancer ◽  
Weight Loss ◽  
Disseminated Intravascular Coagulation ◽  
Metastatic Prostate Cancer ◽  
Degradation Products ◽  
Specific Antigen ◽  
Mass Effect ◽  
Whole Body ◽  
Initial Manifestation ◽  
Intravascular Coagulation

A 70-year-old male presented with hematuria and bruising of arms and legs for the last three days. He also complained of urinary frequency and hesitancy and weight loss of 40 pounds over a span of four months. Initial blood tests showed prothrombin time (PT) of 25.1 seconds, international normalized ratio (INR) of 2.5, partial thromboplastin time (PTT) of 43.9 seconds, fibrinogen of 60 mg/dl, fibrin degradation products (FDP) of more than 20 μg/ml, and platelets of 88,000/μl. The impression was disseminated intravascular coagulation (DIC). A search was initiated to determine the underlying etiology precipitating DIC. Due to urinary symptoms and weight loss, prostate-specific antigen (PSA) was ordered. PSA was elevated at 942 μg/dl. Computed tomography (CT) of the abdomen and pelvis without contrast showed an enlarged prostate with mass effect on the bladder base, left-sided hydronephrosis, and numerous enlarged pelvic lymph nodes. A bone scan of the whole body showed increased sclerosis of the L3 vertebral body. There was a concern for metastatic prostate cancer precipitating DIC. On first admission, our patient’s DIC was stabilized with FFP and cryoprecipitate transfusions. He refused chemotherapy, and degarelix was not economically feasible. Accordingly, he was started on androgen deprivation therapy (ADT), bicalutamide, and leuprolide as an inpatient, pending the tissue biopsy. The patient refused a prostate biopsy. A bone marrow biopsy was performed which confirmed metastatic prostate adenocarcinoma. The patient was stable for discharge with a plan for outpatient chemotherapy. Subsequently, he was lost to follow-up with the oncology. Six months after the initial presentation, he was readmitted with hematuria. Repeat PSA worsened to 1,970 μg/dl. Blood work was consistent with acute DIC. He refused chemotherapy again. So, he was restarted on ADT. However, his hematuria and DIC panel were worsening. He was emergently started on docetaxel as an inpatient (after patient agreement). Within three days of starting chemotherapy, his hematuria resolved and DIC panel showed consistent improvement.

scholarly journals Effects of BI 655064, an antagonistic anti-CD40 antibody, on clinical and biomarker variables in patients with active rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase IIa study

2019 ◽  
Vol 78 (6) ◽  
pp. 754-760 ◽  
Author(s):  
Sudha Visvanathan ◽  
Stefan Daniluk ◽  
Rafał Ptaszyński ◽  
Ulf Müller-Ladner ◽  
Meera Ramanujam ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Resorption ◽  
Primary Endpoint ◽  
Study Drug ◽  
Nuclear Factor Κb ◽  
Inadequate Response ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Autoantibody Production ◽  
Bone Resorption Markers

ObjectiveTo evaluate the safety, efficacy and therapeutic mechanism of BI 655064, an antagonistic anti-CD40 monoclonal antibody, in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX-IR).MethodsIn total, 67 patients were randomised to receive weekly subcutaneous doses of 120 mg BI 655064 (n=44) or placebo (n=23) for 12 weeks. The primary endpoint was the proportion of patients who achieved 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Safety was assessed in patients who received at least one dose of study drug.ResultsAt week 12, the primary endpoint was not met, with 68.2% of patients treated with BI 655064 achieving an ACR20 vs 45.5% with placebo (p=0.064); using Bayesian analysis, the posterior probability of seeing a difference greater than 35% was 42.9%. BI 655064 was associated with greater changes in CD40–CD40L pathway-related markers, including reductions in inflammatory and bone resorption markers (interleukin-6, matrix metalloproteinase-3, receptor activator of nuclear factor-κB ligand), concentration of autoantibodies (immunoglobulin [Ig]G rheumatoid factor [RF], IgM RF, IgA RF) and CD95+ activated B-cell subsets. No serious adverse events (AEs) related to BI 655064 treatment or thromboembolic events occurred; reported AEs were mainly of mild intensity.ConclusionAlthough blockade of the CD40–CD40L pathway with BI 655064 in MTX-IR patients with RA resulted in marked changes in clinical and biological parameters, including reductions in activated B-cells, autoantibody production and inflammatory and bone resorption markers, with a favourable safety profile, clinical efficacy was not demonstrated in this small phase IIa study.Trial registration numberNCT01751776

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