The Experts below are selected from a list of 243 Experts worldwide ranked by ideXlab platform
Karim Fizazi - One of the best experts on this subject based on the ideXlab platform.
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orteronel plus Prednisone in patients with chemotherapy naive metastatic castration resistant prostate cancer elm pc 4 a double blind multicentre phase 3 randomised placebo controlled trial
Lancet Oncology, 2015Co-Authors: Fred Saad, Karim Fizazi, Viorel Jinga, Eleni Efstathiou, Peter C C Fong, Lowell L Hart, Robert Jones, R Mcdermott, Manfred Wirth, Kazuhiro SuzukiAbstract:Summary Background Orteronel is an investigational, partially selective inhibitor of CYP 17,20-lyase in the androgen signalling pathway, a validated therapeutic target for metastatic castration-resistant prostate cancer. We assessed orteronel in chemotherapy-naive patients with metastatic castration-resistant prostate cancer. Methods In this phase 3, double-blind, placebo-controlled trial, we recruited patients with progressive metastatic castration-resistant prostate cancer and no previous chemotherapy from 324 study centres (ie, hospitals or large urologic or group outpatient offices) in 43 countries. Eligible patients were randomly assigned in a 1:1 ratio to receive either 400 mg orteronel plus 5 mg Prednisone twice daily or placebo plus 5 mg Prednisone twice daily. Randomisation was done centrally with an interactive voice response system and patients were stratified by region (Europe, North America, and not Europe or North America) and the presence or absence of radiographic disease progression at baseline. The two primary endpoints were radiographic progression-free survival and overall survival, determined in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01193244. Findings From Oct 31, 2010, to June 29, 2012, 2353 patients were assessed for eligibility. Of those, 1560 were randomly assigned to receive either orteronel plus Prednisone (n=781) or placebo plus Prednisone (n=779). The clinical cutoff date for the final analysis was Jan 15, 2014 (with 611 deaths). Median follow-up for radiographic progression-free survival was 8·4 months (IQR 3·7–16·6). Median radiographic progression-free survival was 13·8 months (95% CI 13·1–14·9) with orteronel plus Prednisone and 8·7 months (8·3–10·9) with placebo plus Prednisone (hazard ratio [HR] 0·71, 95% CI 0·63–0·80; p vs 14 [2%] of 770 patients in the placebo plus Prednisone group), increased amylase (77 [10%] vs nine [1%]), fatigue (50 [6%] vs 14 [2%]), and pulmonary embolism (40 [5%] vs 27 [4%]). Serious adverse events were reported in 358 [46%] patients receiving orteronel plus Prednisone and in 292 [38%] patients receiving placebo plus Prednisone. Interpretation In chemotherapy-naive patients with metastatic castration-resistant prostate cancer, radiographic progression-free survival was prolonged with orteronel plus Prednisone versus placebo plus Prednisone. However, no improvement was noted in the other primary endpoint, overall survival. Orteronel plus Prednisone was associated with increased toxic effects compared with placebo plus Prednisone. On the basis of these and other data, orteronel is not undergoing further development in metastatic castration-resistant prostate cancer. Funding Millennium Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
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updated interim efficacy analysis and long term safety of abiraterone acetate in metastatic castration resistant prostate cancer patients without prior chemotherapy cou aa 302
European Urology, 2014Co-Authors: Dana E Rathkopf, Paul N Mainwaring, Karim Fizazi, Matthew R Smith, Johann S De Bono, Christopher J Logothetis, Neal D Shore, Paul De Souza, Peter F A Mulders, John D HainsworthAbstract:Background Abiraterone acetate (an androgen biosynthesis inhibitor) plus Prednisone is approved for treating patients with metastatic castration-resistant prostate cancer (mCRPC). Study COU-AA-302 evaluated abiraterone acetate plus Prednisone versus Prednisone alone in mildly symptomatic or asymptomatic patients with progressive mCRPC without prior chemotherapy.
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effect of abiraterone acetate on fatigue in patients with metastatic castration resistant prostate cancer after docetaxel chemotherapy
Annals of Oncology, 2013Co-Authors: Cora N Sternberg, Arturo Molina, Scott North, Paul N Mainwaring, Karim Fizazi, Margaret Rothman, Dennis D Gagnon, Thian Kheoh, C M Haqq, Charles S CleelandAbstract:Fatigue is a common, debilitating side-effect of prostate cancer and its treatment. Patient-reported fatigue was evaluated as part of COU-AA-301, a randomized, placebo-controlled, phase III trial of abiraterone acetate and Prednisone versus placebo and Prednisone in metastatic castration-resistant prostate cancer (mCRPC) patients after docetaxel chemotherapy. This is the first phase III study in advanced prostate cancer to evaluate fatigue outcomes using a validated fatigue-specific instrument. The Brief Fatigue Inventory (BFI) questionnaire was used to measure patient-reported fatigue intensity and fatigue interference with activities of daily life. All analyses were conducted using prespecified responder definitions of clinically meaningful changes. A total of 797 patients were randomized to abiraterone acetate and Prednisone, and 398 were randomized to placebo and Prednisone. Compared with Prednisone alone, in patients with clinically significant fatigue at baseline, abiraterone acetate and Prednisone significantly increased the proportion of patients reporting improvement in fatigue intensity (58.1% versus 40.3%, P = 0.0001), improved fatigue interference (55.0% versus 38.0%, P = 0.0075), and accelerated improvement in fatigue intensity (median 59 days versus 194 days, P = 0.0155). In patients with mCRPC progressing after docetaxel chemotherapy, abiraterone acetate and Prednisone yielded clinically meaningful improvements in patient-reported fatigue compared with Prednisone alone.
Amelia Evoli - One of the best experts on this subject based on the ideXlab platform.
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long term effect of thymectomy plus Prednisone versus Prednisone alone in patients with non thymomatous myasthenia gravis 2 year extension of the mgtx randomised trial
Lancet Neurology, 2019Co-Authors: Gil I Wolfe, Greg Minisman, Claudio Mazia, Jeannine M Heckmann, Henry J. Kaminski, Inmaculada Aban, Joel Oger, Alexander Marx, Philipp Ströbel, Amelia EvoliAbstract:Summary Background The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) showed that thymectomy combined with Prednisone was superior to Prednisone alone in improving clinical status as measured by the Quantitative Myasthenia Gravis (QMG) score in patients with generalised non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events. Methods We did a rater-blinded 2-year extension study at 36 centres in 15 countries for all patients who completed the randomised controlled MGTX and were willing to participate. MGTX patients were aged 18 to 65 years at enrolment, had generalised non-thymomatous myasthenia gravis of less than 5 years' duration, had acetylcholine receptor antibody titres of 1·00 nmol/L or higher (or concentrations of 0·50–0·99 nmol/L if diagnosis was confirmed by positive edrophonium or abnormal repetitive nerve stimulation, or abnormal single fibre electromyography), had Myasthenia Gravis Foundation of America Clinical Classification Class II–IV disease, and were on optimal anticholinesterase therapy with or without oral corticosteroids. In MGTX, patients were randomly assigned (1:1) to either thymectomy plus Prednisone or Prednisone alone. All patients in both groups received oral Prednisone at doses titrated up to 100 mg on alternate days until they achieved minimal manifestation status. The primary endpoints of the extension phase were the time-weighted means of the QMG score and alternate-day Prednisone dose from month 0 to month 60. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00294658. It is closed to new participants, with follow-up completed. Findings Of the 111 patients who completed the 3-year MGTX, 68 (61%) entered the extension study between Sept 1, 2009, and Aug 26, 2015 (33 in the Prednisone alone group and 35 in the Prednisone plus thymectomy group). 50 (74%) patients completed the 60-month assessment, 24 in the Prednisone alone group and 26 in the Prednisone plus thymectomy group. At 5 years, patients in the thymectomy plus Prednisone group had significantly lower time-weighted mean QMG scores (5·47 [SD 3·87] vs 9·34 [5·08]; p=0·0007) and mean alternate-day Prednisone doses (24 mg [SD 21] vs 48 mg [29]; p=0·0002) than did those in the Prednisone alone group. 14 (42%) of 33 patients in the Prednisone group, and 12 (34%) of 35 in the thymectomy plus Prednisone group, had at least one adverse event by month 60. No treatment-related deaths were reported during the extension phase. Interpretation At 5 years, thymectomy plus Prednisone continues to confer benefits in patients with generalised non-thymomatous myasthenia gravis compared with Prednisone alone. Although caution is appropriate when generalising our findings because of the small sample size of our study, they nevertheless provide further support for the benefits of thymectomy in patients with generalised non-thymomatous myasthenia gravis. Funding National Institutes of Health, National Institute of Neurological Disorders and Stroke.
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randomized trial of thymectomy in myasthenia gravis
The New England Journal of Medicine, 2016Co-Authors: Gil I Wolfe, Greg Minisman, Claudio Mazia, Jeannine M Heckmann, Henry J. Kaminski, Inmaculada Aban, Joel Oger, Alexander Marx, Philipp Ströbel, Amelia EvoliAbstract:BackgroundThymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus Prednisone with Prednisone alone. MethodsWe compared extended transsternal thymectomy plus alternate-day Prednisone with alternate-day Prednisone alone. Patients 18 to 65 years of age who had generalized nonthymomatous myasthenia gravis with a disease duration of less than 5 years were included if they had Myasthenia Gravis Foundation of America clinical class II to IV disease (on a scale from I to V, with higher classes indicating more severe disease) and elevated circulating concentrations of acetylcholine-receptor antibody. The primary outcomes were the time-weighted average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with higher scores indicating more severe disease) over a 3-year period, as assessed by means of blinded rating, and the time-weighted average required dose of prednison...
Carlo Salvarani - One of the best experts on this subject based on the ideXlab platform.
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glucocorticoid dosages and acute phase reactant levels at giant cell arteritis flare in a randomized trial of tocilizumab
Arthritis & Rheumatism, 2019Co-Authors: John H Stone, Katie Tuckwell, Sophie Dimonaco, Micki Klearman, Martin Aringer, Daniel Engelbert Blockmans, Elisabeth Brouwer, Bhaskar Dasgupta, Juergen Rech, Carlo SalvaraniAbstract:OBJECTIVE: To evaluate glucocorticoid doses and serological findings in patients with giant cell arteritis (GCA) flares. METHODS: Patients with GCA were randomly assigned to receive double-blind dosing with subcutaneous tocilizumab (TCZ) 162 mg weekly plus 26-week Prednisone (TCZ-QW+Pred-26), every-other-week TCZ plus 26-week Prednisone (TCZ-Q2W+Pred-26), placebo plus 26-week Prednisone (PBO+Pred-26), or placebo plus 52-week Prednisone (PBO+Pred-52). Outcomes were Prednisone dose, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR) at the time of flare and remission during 52 weeks. RESULTS: One hundred patients received TCZ-QW+Pred-26, 49 received TCZ-Q2W+Pred-26, 50 received PBO+Pred-26, and 51 received PBO+Pred-52. Among 149 TCZ-treated patients, 36 (24%) experienced flare, 23 (64%) of whom were still receiving Prednisone (median dose, 2.0 mg/day). Among 101 PBO+Pred-treated patients, 59 (58%) experienced flare, 45 (76%) of whom were receiving Prednisone (median dose, 5.0 mg/day). Many flares occurred while patients were taking more than 10 mg/day Prednisone: 9 (25%) in the TCZ groups and 13 (22.0%) in the placebo groups. Thirty-three flares (92%) in TCZ-treated groups and 20 (34%) in PBO+Pred-treated groups occurred with normal CRP. More than half the PBO+Pred-treated patients had elevated CRP without flare. Benefits of the combination of TCZ plus Prednisone over Prednisone alone for remission induction were apparent by 8 weeks. CONCLUSION: Most GCA flares occurred while patients were still receiving Prednisone. Acute-phase reactants were not reliable indicators of flare in patients treated with TCZ plus Prednisone or with Prednisone alone. The addition of TCZ to Prednisone facilitates earlier GCA control. This article is protected by copyright. All rights reserved.
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glucocorticoid dosages and acute phase reactant levels at giant cell arteritis flare in a randomized trial of tocilizumab
Arthritis & Rheumatism, 2019Co-Authors: John H Stone, Katie Tuckwell, Sophie Dimonaco, Micki Klearman, Martin Aringer, Daniel Engelbert Blockmans, Elisabeth Brouwer, Bhaskar Dasgupta, Juergen Rech, Carlo SalvaraniAbstract:OBJECTIVE: This study was undertaken to evaluate glucocorticoid dosages and serologic findings in patients with giant cell arteritis (GCA) flares. METHODS: Patients with GCA were randomly assigned to receive double-blind dosing with either subcutaneous tocilizumab (TCZ) 162 mg weekly plus 26-week Prednisone taper (TCZ-QW + Pred-26), every-other-week TCZ plus 26-week Prednisone taper (TCZ-Q2W + Pred-26), placebo plus 26-week Prednisone taper (PBO + Pred-26), or placebo plus 52-week Prednisone taper (PBO + Pred-52). Outcome measures were Prednisone dosage, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR) at the time of flare. RESULTS: One hundred patients received TCZ-QW + Pred-26, 49 received TCZ-Q2W + Pred-26, 50 received PBO + Pred-26, and 51 received PBO + Pred-52. Of the 149 TCZ-treated patients, 36 (24%) experienced flare, 23 (64%) of whom were still receiving Prednisone (median dosage 2.0 mg/day). Among 101 PBO + Pred-treated patients, 59 (58%) experienced flare, 45 (76%) of whom were receiving Prednisone (median dosage 5.0 mg/day). Many flares occurred while patients were taking >10 mg/day Prednisone: 9 (25%) in the TCZ groups and 13 (22%) in the placebo groups. Thirty-three flares (92%) in TCZ-treated groups and 20 (34%) in PBO + Pred-treated groups occurred with normal CRP levels. More than half of the PBO + Pred-treated patients had elevated CRP levels without flares. Benefits of the TCZ and Prednisone combination over Prednisone alone for remission induction were apparent by 8 weeks. CONCLUSION: Most GCA flares occurred while patients were still receiving Prednisone. Acute-phase reactant levels were not reliable indicators of flare in patients treated with TCZ plus Prednisone or with Prednisone alone. The addition of TCZ to Prednisone facilitates earlier GCA control.
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Prednisone plus methotrexate for polymyalgia rheumatica a randomized double blind placebo controlled trial
Annals of Internal Medicine, 2004Co-Authors: Roberto Caporali, Carlo Salvarani, M A Cimmino, Gianfranco Ferraccioli, Roberto Gerli, Catherine Klersy, Carlomaurizio MontecuccoAbstract:BACKGROUND: Steroids are the standard treatment for polymyalgia rheumatica. The efficacy of the candidate drug methotrexate has not yet been demonstrated in controlled studies. OBJECTIVE: To compare the efficacy and safety of Prednisone plus methotrexate and Prednisone alone in patients with polymyalgia rheumatica. DESIGN: Multicenter randomized, double-blind, placebo-controlled trial. SETTING: 5 Italian rheumatology clinics. PATIENTS: 72 patients with newly diagnosed polymyalgia rheumatica. MEASUREMENTS: The proportion of patients no longer taking Prednisone, the number of flare-ups, and the cumulative Prednisone dose after 76 weeks. INTERVENTION: Prednisone dosage (25 mg/d) was tapered to 0 mg/d within 24 weeks and was adjusted if flare-ups occurred. Oral methotrexate (10 mg) or placebo, with folinic acid supplementation (7.5 mg), was given weekly for 48 weeks. RESULTS: Twenty-eight of 32 patients in the methotrexate group and 16 of 30 patients in the placebo group were no longer taking Prednisone at 76 weeks (P = 0.003). The risk difference was 34 percentage points (95% CI, 11 to 53 percentage points). Similar results were obtained after adjustment for C-reactive protein level and duration of symptoms in a multivariate model. Fifteen of 32 patients in the methotrexate group and 22 of 30 patients in the placebo group had at least 1 flare-up by the end of follow-up (P = 0.04). The median Prednisone dose was 2.1 g in the methotrexate group and 2.97 g in the placebo group (P = 0.03). The rate and severity of adverse events were similar. LIMITATIONS: Follow-up was short, and a high dose of folinic acid and a relatively high starting dosage of Prednisone were used. Ten of 72 patients (14%) discontinued treatment or were lost to follow-up. CONCLUSIONS: Prednisone plus methotrexate is associated with shorter Prednisone treatment and steroid sparing. It may be useful in patients at high risk for steroid-related toxicity.
Lina Asmar - One of the best experts on this subject based on the ideXlab platform.
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phase iii study of mitoxantrone plus low dose Prednisone versus low dose Prednisone alone in patients with asymptomatic hormone refractory prostate cancer
The Journal of Urology, 2002Co-Authors: William R Berry, Shaker R Dakhil, Manuel Modiano, Maryann Gregurich, Lina AsmarAbstract:ABSTRACTPurpose: We compared median time to treatment failure of men with asymptomatic, hormone refractory, progressive prostate cancer treated with mitoxantrone plus Prednisone versus Prednisone alone.Materials and Methods: In a multicenter phase III trial 120 men with asymptomatic, progressive, hormone refractory prostate cancer were randomly assigned to treatment with mitoxantrone and Prednisone or Prednisone alone. Patients received 12 mg./m.2 mitoxantrone intravenously once every 3 weeks for 6 cycles and 5 mg. Prednisone twice daily with or without mitoxantrone. Time to treatment failure was assessed as an aggregate end point comprised of time to disease progression, time to toxicity or death, or time to initiation of alternate therapy.Results: Median followup was 21.8 months. Median time to treatment failure and median time to progression were the same: time to treatment failure and time to progression in the mitoxantrone and Prednisone group was 8.1 months compared to 4.1 months in the Prednisone a...
Evan Y Yu - One of the best experts on this subject based on the ideXlab platform.
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a randomized phase 2 study of a hsp27 targeting antisense apatorsen with Prednisone versus Prednisone alone in patients with metastatic castration resistant prostate cancer
Investigational New Drugs, 2018Co-Authors: Evan Y Yu, Susan Ellard, Sebastien J Hotte, Joel Roger Gingerich, Anthony M Joshua, Martin E GleaveAbstract:Purpose Heat shock protein 27 (Hsp27) is implicated in prostate cancer progression. Apatorsen is a second generation phosphorothioate antisense inhibitor of Hsp27 expression. We evaluated apatorsen in patients with metastatic castration resistant prostate cancer (mCRPC). Experimental design Eligible patients were randomized 1:1 to receive intravenous apatorsen (3 loading doses of 600 mg within 5–9 days followed by weekly doses of 1000 mg) with oral Prednisone 5 mg twice daily or Prednisone alone. The primary endpoint was disease progression at 12 weeks. Crossover from Prednisone alone was allowed after radiographic progression. Results 74 patients received apatorsen + Prednisone (n = 36) or Prednisone alone (n = 38). Twenty-five patients crossed-over to receive apatorsen + Prednisone. Apatorsen treated patients received a median of 19 infusions. 50% of apatorsen + Prednisone patients (95% CI: 32.9%, 67.1%) compared with 42% of Prednisone patients (95% CI: 26.3%, 59.2%) did not have disease progression at week 12 (P = 0.33). A PSA decline of ≥50% was observed in 47% of apatorsen + Prednisone and 24% of Prednisone patients (P = 0.04), with a median duration of response of 24.1 weeks (95% CI: 12.0, 52) and 14.0 weeks (95% CI: 4.0, 44.4), respectively. A PSA decline of ≥50% was observed in 5 patients (20%) that received cross-over apatorsen. Infusion reactions were the most commonly reported adverse event occurring in 77% of apatorsen-treated patients. Conclusions Apatorsen + Prednisone did not change the proportion of CRPC patients without disease progression at 12 weeks compared to Prednisone but was associated with significant PSA declines. Further evaluation of Hsp27 targeting in prostate cancer is warranted.
