Modafinil for fatigue associated with docetaxel-based chemotherapy: A randomized controlled trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15152-e15152
Author(s):  
Elizabeth J. Hovey ◽  
Paul L. De Souza ◽  
Gavin M. Marx ◽  
Tal Rapke ◽  
Phillip Parente ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Primary Endpoint ◽  
Controlled Trial ◽  
Area Under The Curve ◽  
Standard Of Care ◽  
Study Medication ◽  
Double Blind ◽  
Chemotherapy Patients ◽  
Castrate Resistant ◽  
High Level

e15152 Background: Docetaxel is the standard of care for castrate-resistant prostate cancer, but is associated with a high level of fatigue, limiting dosage and leading to premature withdrawal from therapy. Methods: A multicenter, randomized, double-blind, placebo-controlled, parallel group study in patients with metastatic prostate or breast cancer suffering significant chemotherapy-related fatigue whilst undergoing docetaxel-based chemotherapy. Patients were enrolled at the start of their 3rdor subsequent cycles of docetaxel which was continued for up to four further cycles (defined here as ‘treatment periods’). Patients were randomized 2:1 to receive modafinil 200mg daily or placebo for 15 days during each treatment period. Fatigue was evaluated by the MD Anderson Symptom Inventory (MDASI). The primary endpoint was MDASI area under the curve (AUC) during the first 7 days of study medication for the first two treatment periods (possible range 0-70). Other validated tools were used to record disturbances in sleep, mood and functional status. Results: Eighty-three patients (65 with prostate cancer) were randomized and received at least one dose of study medication. The number of grade 3 or 4 adverse events (AEs) was 16/55 (29.1%) in the modafinil group and 5/28 (17.9%) in the placebo group. The toxicity profile was largely consistent with docetaxel-based chemotherapy and with previously reported AEs associated with modafinil use in the community; 11 AEs were possibly related to docetaxel; 1 to modafinil and 9 to neither treatment. Conclusions: Assessing and managing chemotherapy-related fatigue remains a major challenge. Despite not reaching the primary endpoint, there was a consistent trend towards improvement of chemotherapy-related fatigue in the modafinil arm. Further studies are needed to better address the significant symptom of docetaxel-related fatigue. Funding sanofi-aventis; Study ID NCT00917748. [Table: see text]

Modafinil for fatigue associated with docetaxel-based chemotherapy: A randomized controlled trial.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 211-211
Author(s):  
Elizabeth J. Hovey ◽  
Paul L. De Souza ◽  
Gavin M. Marx ◽  
Phillip Parente ◽  
Tal Rapke ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Controlled Trial ◽  
Area Under The Curve ◽  
Study Medication ◽  
Double Blind ◽  
Patients With Cancer ◽  
Parallel Group ◽  
Grade 3 ◽  
Chemotherapy Patients ◽  
Md Anderson

211 Background: Chemotherapy-induced fatigue is a common complaint for patients with cancer. We investigated whether modafinil, a psychostimulant, could reduce fatigue in patients on chemotherapy. Methods: A multicenter, randomized, double-blind, placebo-controlled, parallel group study was conducted in patients with metastatic prostate or breast cancer suffering significant chemotherapy-related fatigue whilst undergoing docetaxel-based chemotherapy. Patients were enrolled at the start of their 3rdor subsequent cycles of docetaxel which was continued for up to four further cycles (defined here as ‘treatment periods’). Patients were randomized 2:1 to receive modafinil 200mg daily or placebo for 15 days during each treatment period. Fatigue was evaluated by the MD Anderson Symptom Inventory (MDASI). The primary endpoint was MDASI area under the curve (AUC) during the first 7 days of study medication for the first two treatment periods (possible range 0-70). Other validated tools were used to record disturbances in sleep, mood and functional status. Results: Eighty-three patients (65 with prostate cancer) were randomized and received at least one dose of study medication. The number of grade 3 or 4 adverse events (AEs) was 16/55 (29.1%) in the modafinil group and 5/28 (17.9%) in the placebo group. The toxicity profile was largely consistent with docetaxel-based chemotherapy and with previously reported AEs associated with modafinil use in the community; 11 AEs were possibly related to docetaxel; 1 to modafinil and 9 to neither treatment. Conclusions: Managing chemotherapy-related fatigue remains a major challenge. Despite not reaching the primary endpoint, there was a consistent trend towards improvement of chemotherapy-related fatigue in the modafinil arm. Further studies are needed to better understand the clinical implications of these findings. Funding sanofi-aventis; Study ID NCT00917748 . [Table: see text]

Results from a phase 3, randomized, double-blind, multicenter, placebo-controlled trial of orteronel (TAK-700) plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) that has progressed during or following docetaxel-based therapy (ELM-PC 5 trial).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 7-7 ◽  
Author(s):  
Robert Dreicer ◽  
Robert Jones ◽  
Stephane Oudard ◽  
Eleni Efstathiou ◽  
Fred Saad ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Primary Endpoint ◽  
Controlled Trial ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Castration Resistant ◽  
Key Enzyme

7^ Background: Orteronel is an investigational, non-steroidal selective inhibitor of 17,20-lyase; a key enzyme in the production of steroidal hormones. Methods: Eligible men with metastatic castration-resistant prostate cancer (mCRPC) had progressive disease (PD; radiographic or prostate-specific antigen), castrate levels of testosterone, and had received more than or equal to 360 mg/m2docetaxel within the prior 6 months. Prior orteronel, abiraterone, or ketoconazole was not permitted. Patients were randomized 2:1 to continuous 28-day cycles of oral orteronel 400 mg BID + prednisone 5 mg BID, or placebo + prednisone without regard to food. Primary endpoint: overall survival (OS); other key endpoints: radiographical progression-free survival (rPFS), 50% or more PSA decrease at 12 weeks, pain response at 12 weeks and safety (NCT01193257). Results: One thousand ninety nine patients were randomized.The study was terminated for failing to meet its primary endpoint: median overall survival (OS) was 17.0 months (95% CI 15.2, 19.9) in patients receiving orteronel versus 15.2 months (95% CI 13.5, 16.9) in those receiving placebo (HR: 0.886 [95% CI: 0.739, 1.062]; P=0.1898). Substantial regional differences were seen in OS benefit: median OS (orteronel vs. placebo) was 20.9 vs. 16.9 mo (HR: 0.889) in North America (n=112), 18.3 vs. 17.8 mo (HR: 1.048) in Europe (n=590), and 15.3 vs 10.1 mo (HR: 0.709) in the rest of the world (n=397). In the overall population, rPFS was significantly improved in the orteronel arm, with a median of 8.3 months vs. 5.7 months in the placebo arm (HR: 0.76 [95% CI: 0.653, 0.885]; P=0.00038). Drug-related adverse events (AEs; any grade) included (orteronel/placebo) nausea (30/16%), vomiting (23/8%), fatigue (17/11%), and diarrhea (16/9%); grade 3 or higher drug-related AEs included increased lipase (12/less than 1%), increased amylase (8/less than 1%), and fatigue (3/3%). Additional sub-analyses looking at potential factors that affected OS will also be reported. Conclusions: Whileorteronel + prednisone did not show a statistically significant overall OS improvement versus placebo + prednisone, rPFS findings and striking regional OS differences suggest that orteronel has clinically meaningful activity. Clinical trial information: NCT01193257.

scholarly journals 225Actinium-labeled prostate-specific membrane antigen targeting peptide induces complete response in a metastatic prostate cancer patient

2021 ◽  
Vol 10 (5) ◽  
pp. 205846012110225
Author(s):  
Omer Aras ◽  
Stefan Harmsen ◽  
Richard Ting ◽  
Haluk B Sayman
Keyword(s):  
Prostate Cancer ◽  
Standard Of Care ◽  
Complete Response ◽  
Prostate Specific Membrane Antigen ◽  
Limited Data ◽  
Castrate Resistant Prostate Cancer ◽  
Targeting Peptide ◽  
Castrate Resistant ◽  
Specific Membrane

Targeted radionuclide therapy has emerged as a promising and potentially curative strategy for high-grade prostate cancer. However, limited data are available on efficacy, quality of life, and pretherapeutic biomarkers. Here, we highlight the case of a patient with prostate-specific membrane antigen (PSMA)-positive metastatic castrate-resistant prostate cancer who displayed complete response to 225Ac-PSMA-617 after having been resistant to standard-of-care therapy, then initially partially responsive but later resistant to subsequent immunotherapy, and resistant to successive 177Lu-PSMA-617. In addition, the patient’s baseline germline mutation likely predisposed him to more aggressive disease.

scholarly journals A novel predictor of clinical progression in patients on active surveillance for prostate cancer

2019 ◽  
Vol 13 (8) ◽  
Author(s):  
Guan Hee Tan ◽  
Antonio Finelli ◽  
Ardalan Ahmad ◽  
Marian Wettstein ◽  
Alexandre Zlotta ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Active Surveillance ◽  
Cox Regression ◽  
Area Under The Curve ◽  
Progression Free Survival ◽  
Roc Curves ◽  
Standard Of Care ◽  
Low Risk ◽  
Clinical Progression

Introduction: Active surveillance (AS) is standard of care in low-risk prostate cancer (PC). This study describes a novel total cancer location (TCLo) density metric and aims to determine its performance in predicting clinical progression (CP) and grade progression (GP).     Methods: This was a retrospective study of patients on AS after confirmatory biopsy (CBx). We excluded patients with Gleason ≥7 at CBx and <2 years follow-up. TCLo was the number of locations with positive cores at diagnosis (DBx) and CBx. TCLo density was TCLo / prostate volume (PV). CP was progression to any active treatment while GP occurred if Gleason ≥7 was identified on repeat biopsy or surgical pathology. Independent predictors of time to CP or GP were estimated with Cox regression. Kaplan-Meier analysis compared progression-free survival curves between TCLo density groups. Test characteristics of TCLo were explored with receiver operating characteristic (ROC) curves.     Results: We included 181 patients who had CBx between 2012-2015, and met inclusion criteria. The mean age of patients was 62.58 years (SD=7.13) and median follow-up was 60.9 months (IQR=23.4). A high TCLo density score (>0.05) was independently associated with time to CP (HR 4.70, 95% CI: 2.62-8.42, p<0.001), and GP (HR 3.85, 95% CI: 1.91-7.73, p<0.001). ROC curves showed TCLo density has greater area under the curve than number of positive cores at CBx in predicting progression.     Conclusion: TCLo density is able to stratify patients on AS for risk of CP and GP. With further validation, it could be added to the decision-making algorithm in AS for low-risk localized PC.

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.

A randomized, double‐blind, placebo‐controlled trial to evaluate the role of curcumin in prostate cancer patients with intermittent androgen deprivation

The Prostate ◽  
2019 ◽  
Vol 79 (6) ◽  
pp. 614-621 ◽  
Author(s):  
Young Hyo Choi ◽  
Deok Hyun Han ◽  
Seon‐woo Kim ◽  
Min‐Ji Kim ◽  
Hyun Hwan Sung ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Controlled Trial ◽  
Androgen Deprivation ◽  
Double Blind ◽  
Double Blind Placebo

scholarly journals An evidence-based review of hyperbaric oxygen for children with cerebral palsy

2001 ◽  
Vol 57 (4) ◽  
pp. 21-22
Author(s):  
F. M. Bischof
Keyword(s):  
Cerebral Palsy ◽  
Pilot Study ◽  
Motor Function ◽  
Controlled Trial ◽  
Evidence Based ◽  
Level Of Evidence ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Children With Cerebral Palsy ◽  
High Level

This paper reviews the evidence in the literature for the use of hypebaric oxygen (HBO) in the treatment of cerebral palsy (CP). To date there are only two published studies on the outcome of HBO administration in CP. A pilot study showed significant improvement in gross motor function but provided a low level of evidence. A recent multicentre, double blind, placebo controlled trial reported similar improvements in both HBO and placebo groups, but no difference between the groups. This study had a high level of evidence. The results suggest that participation in the trial produced clinically important gains in function. The outcome of the study implies that HBO may have a placebo effect in CP.

scholarly journals Regular, sustained-release morphine for chronic breathlessness: a multicentre, double-blind, randomised, placebo-controlled trial

Thorax ◽  
2019 ◽  
Vol 75 (1) ◽  
pp. 50-56 ◽  
Author(s):  
David Currow ◽  
Sandra Louw ◽  
Philip McCloud ◽  
Belinda Fazekas ◽  
John Plummer ◽  
...  
Keyword(s):  
Sustained Release ◽  
Primary Endpoint ◽  
Controlled Trial ◽  
Oral Morphine ◽  
Immediate Release ◽  
Morphine Group ◽  
Double Blind ◽  
Intention To Treat ◽  
Palliative Care Services ◽  
Secondary Endpoints

IntroductionMorphine may decrease the intensity of chronic breathlessness but data from a large randomised controlled trial (RCT) are lacking. This first, large, parallel-group trial aimed to test the efficacy and safety of regular, low-dose, sustained-release (SR) morphine compared with placebo for chronic breathlessness.MethodsMultisite (14 inpatient and outpatient cardiorespiratory and palliative care services in Australia), parallel-arm, double-blind RCT. Adults with chronic breathlessness (modified Medical Research Council≥2) were randomised to 20 mg daily oral SR morphine and laxative (intervention) or placebo and placebo laxative (control) for 7 days. Both groups could take ≤6 doses of 2.5 mg, ‘as needed’, immediate-release morphine (≤15 mg/24 hours) as required by the ethics review board. The primary endpoint was change from baseline in intensity of breathlessness now (0–100 mm visual analogue scale; two times per day diary) between groups. Secondary endpoints included: worst, best and average breathlessness; unpleasantness of breathlessness now, fatigue; quality of life; function; and harms.ResultsAnalysed by intention-to-treat, 284 participants were randomised to morphine (n=145) or placebo (n=139). There was no difference between arms for the primary endpoint (mean difference −0.15 mm (95% CI −4.59 to 4.29; p=0.95)), nor secondary endpoints. The placebo group used more doses of oral morphine solution during the treatment period (mean 8.7 vs 5.8 doses; p=0.001). The morphine group had more constipation and nausea/vomiting. There were no cases of respiratory depression nor obtundation.ConclusionNo differences were observed between arms for breathlessness, but the intervention arm used less rescue immediate-release morphine.Trial registration numberACTRN12609000806268.

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