PURPOSE: The combination of zanubrutinib plus obinutuzumab (ZO) was found to be well tolerated with an early signal of efficacy in a phase Ib study. ROSEWOOD is a phase II, randomized study that assessed the efficacy and safety of ZO versus obinutuzumab in patients with relapsed/refractory (R/R) follicular lymphoma (FL). METHODS: Patients with R/R FL who had received ≥2 lines of therapy, including an anti-CD20 antibody and an alkylating agent, were randomly assigned 2:1 to receive ZO or obinutuzumab (O). The primary end point was overall response rate (ORR) by independent central review (ICR). Secondary end points included duration of response (DOR), progression-free survival (PFS), overall survival, and safety. RESULTS: A total of 217 patients were randomized (ZO, 145; O, 72). Median study follow-up was 20.2 months. The study met its primary end point: ORR by ICR was 69% (ZO) versus 46% (O; P = .001). Complete response rate was 39% (ZO) versus 19% (O); 18-month DOR rate was 69% (ZO) versus 42% (O). Median PFS was 28.0 months (ZO) versus 10.4 months (O; hazard ratio, 0.50 [95% CI, 0.33 to 0.75]; P < .001). The most common adverse events with ZO were thrombocytopenia, neutropenia, diarrhea, and fatigue; incidences of atrial fibrillation and major hemorrhage were 3% and 1%, respectively. CONCLUSION: The combination of ZO met its primary end point of a superior ORR versus O, and demonstrated meaningful activity and a manageable safety profile in patients with R/R FL. ZO had a favorable benefit-risk profile compared with O, and represents a potential combination therapy for patients with R/R FL.

• MeSH
• folikulární lymfom * MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• lidé MeSH
• piperidiny * MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   MeSH
• pyrazoly * MeSH
• pyrimidiny * MeSH
• rituximab MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: In a randomized phase II trial in metastatic renal cell carcinoma (mRCC), objective response rate was significantly higher with axitinib versus placebo titration (54% vs. 34%; 1-sided P = .019). PATIENTS AND METHODS: Treatment-naive patients with mRCC (n = 213) received axitinib 5 mg twice per day (b.i.d.) for 4 weeks. Patients meeting dose titration criteria were randomized to receive axitinib 5 mg b.i.d. with axitinib or placebo titration (n = 56 each); 91 patients ineligible for randomization continued axitinib 5 mg b.i.d.; 10 discontinued before randomization. RESULTS: Median overall survival (95% confidence interval [CI]) was 42.7 months (24.7-not estimable) with axitinib titration versus 30.4 months (23.7-45.0) with placebo titration (stratified hazard ratio, 0.785; 95% CI, 0.485-1.272; 1-sided P = .162), and 41.6 months (95% CI, 33.0-not estimable) in nonrandomized patients. Safety data were consistent with previous reports. CONCLUSION: Median overall survival was numerically longer in patients with first-line mRCC who received axitinib versus placebo titration. No new safety signal was observed after long-term axitinib treatment in first-line mRCC.

• MeSH
• analýza přežití MeSH
• dospělí MeSH
• dvojitá vazba (komunikace) MeSH
• imidazoly aplikace a dávkování   terapeutické užití   MeSH
• indazoly aplikace a dávkování   terapeutické užití   MeSH
• inhibitory angiogeneze aplikace a dávkování   terapeutické užití   MeSH
• karcinom z renálních buněk farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádory ledvin farmakoterapie   MeSH
• přežití bez známek nemoci MeSH
• rozvrh dávkování léků MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Research Support, N.I.H., Extramural MeSH

Cíl: Bylo prokázáno, že perorálně podávané přímé inhibitory trombinu a anti-Xa inhibitory jsou účinné v prevenci a léčbě žilní tromboembolie i v prevenci embolických příhod u fibrilace síní. Studie z poslední doby prokázaly, že podávání dabigatranu může být spojeno se zvýšeným výskytem infarktu myokardu (IM). Riziko koronárních příhod při užívání jiných léků zatím nebylo přesně určeno. Cílem této studie je stanovit riziko koronárních příhod v souvislosti s užíváním čtyř nových antitrombotik. Design studie: Meta-analýza publikovaných srovnání různých způsobů léčby. Zdroje údajů a výběr studií: Výsledky randomizovaných kontrolovaných studií (randomised controlled trials, RCT) s ximelagatranem, dabigatranem, rivaroxabanem a apixabanem byly získány formou rešerše databáze PubMed (únor 2012) a sdělení na významných kongresech konaných v roce 2011. Ke stanovení účinku těchto léků na výskyt IM nebo akutního koronárního syndromu (IM/AKS), komplikací závažného krvácení a celkové mortality byl použit model náhodných účinků. Výsledky: Ve 28 RCT (n = 138 948) bylo riziko IM/AKS vyšší u dabigatranu (OR 1,30; 95 % CI 1,04 až 1,63; p = 0,021), ale nižší u rivaroxabanu (OR 0,78; 95 % CI 0,69 až 0,89; p < 0,001). V případě ximelagatranu bylo prokázáno vyšší riziko IM/AKS, které nebylo statisticky významné, přičemž u apixabanu byla prokázána nevýznamně nižší pravděpodobnost rizika. Z RCT hodnotících riziko IM/AKS u všech čtyř léků vykazovaly heterogenitu údajů pouze studie s ximelagatranem. Výskyt komplikací závažného krvácení se mezi jednotlivými léky značně lišil. Zajímavé bylo zjištění, že hodnocené léky byly spojeny s nízkou celkovou mortalitou, bez rozdílů mezi studiemi. Závěry: Riziko koronárních příhod bylo statisticky významně vyšší v případě dabigatranu a vyšší – ne však statisticky významně – u ximelagatranu. Riziko bylo naopak nižší u inhibitorů anti-Xa. Celková mortalita byla u pacientů užívajících nová antitrombotika nižší. Tyto informace by mohly být užitečné při volbě léku pro specifické podskupiny pacientů vyžadující antikoagulaci.

Aim: Oral direct thrombin inhibitors and anti-Xa inhibitors have been shown to be effective in preventing and treating venous thromboembolism as well as in preventing embolic events in atrial fibrillation. Recent studies have shown that dabigatran administration may be associated with increased rates of myocardial infarction (MI). The risk of coronary events with other agents has not yet been determined precisely. The aim of this study is to ascertain the risk of coronary events in association with the use of four novel antithrombotic agents. Study design: Meta-analysis of published comparisons of different methods of treatment. Sources of data and study selection: Results of randomized controlled trials (RCTs) on ximelagatran, dabigatran, rivaroxaban, and apixaban were obtained by searching the PubMed database (February 2012) and papers from major congresses held in the year 2011. The random-effects model was used to ascertain the effect of these agents on MI or acute coronary syndrome (MI/ACS), major bleeding complications, and all-cause mortality. Results: In 28 RCTs (n = 138 948), the risk of MI/ACS was higher for dabigatran (OR 1.30; 95% CI 1.04 to 1.63; p = 0.021), but lower for rivaroxaban (OR 0.78; 95% CI 0.69 to 0.89; p < 0.001). Ximelagatran was shown to have a higher risk for MI/ACS that was not statistically significant; apixaban demonstrated a non-significantly lower likelihood of risk. Among the RCTs evaluating the risk of MI/ACS for all four agents, only those with ximelagatran showed data heterogeneity. The rates of major bleeding complications varied considerably among the individual agents. Interestingly, the agents evaluated were associated with a low all-cause mortality, without differences among the trials. Conclusions: The risk of coronary events was statistically significantly higher for dabigatran and higher – but not statistically significantly – for ximelagatran. Conversely, the risk was lower for anti-Xa inhibitors. All-cause mortality in patients receiving novel antithrombotic agents was lower. This information may be useful in selecting agents for specific subgroups of patients requiring anticoagulation.

• Klíčová slova
• ximelagatran, apixaban,
• MeSH
• antikoagulancia farmakologie   škodlivé účinky   terapeutické užití   toxicita   MeSH
• azetidiny aplikace a dávkování   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• benzimidazoly aplikace a dávkování   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• benzylaminy aplikace a dávkování   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• dabigatran MeSH
• embolie farmakoterapie   prevence a kontrola   MeSH
• fibrilace síní farmakoterapie   komplikace   MeSH
• hodnocení rizik MeSH
• infarkt myokardu etiologie   MeSH
• lidé MeSH
• morbidita MeSH
• morfoliny aplikace a dávkování   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• mortalita MeSH
• PubMed MeSH
• pyrazoly aplikace a dávkování   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• pyridiny aplikace a dávkování   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• pyridony aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• randomizované kontrolované studie jako téma MeSH
• rivaroxaban MeSH
• statistika jako téma MeSH
• thiofeny aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• tromboembolie farmakoterapie   prevence a kontrola   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

PURPOSE: Linifanib, a potent, selective inhibitor of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptors, has single-agent activity in non-small-cell lung cancer (NSCLC). We evaluated linifanib with carboplatin and paclitaxel as first-line therapy of advanced nonsquamous NSCLC. PATIENTS AND METHODS: Patients with stage IIIB/IV nonsquamous NSCLC were randomly assigned to 3-week cycles of carboplatin (area under the curve 6) and paclitaxel (200 mg/m(2)) with daily placebo (arm A), linifanib 7.5 mg (arm B), or linifanib 12.5 mg (arm C). The primary end point was progression-free survival (PFS); secondary efficacy end points included overall survival (OS) and objective response rate. RESULTS: One hundred thirty-eight patients were randomly assigned (median age, 61 years; 57% men; 84% smokers). Median PFS times were 5.4 months (95% CI, 4.2 to 5.7 months) in arm A (n = 47), 8.3 months (95% CI, 4.2 to 10.8 months) in arm B (n = 44), and 7.3 months (95% CI, 4.6 to 10.8 months) in arm C (n = 47). Hazard ratios (HRs) for PFS were 0.51 for arm B versus A (P = .022) and 0.64 for arm C versus A (P = .118). Median OS times were 11.3, 11.4, and 13.0 months in arms A, B, and C, respectively. HRs for OS were 1.08 for arm B versus A (P = .779) and 0.88 for arm C versus A (P = .650). Both linifanib doses were associated with increased toxicity, including a higher incidence of adverse events known to be associated with VEGF/PDGF inhibition. Baseline plasma carcinoembryonic antigen/cytokeratin 19 fragments biomarker signature was associated with PFS improvement and a trend toward OS improvement with linifanib 12.5 mg. CONCLUSION: Addition of linifanib to chemotherapy significantly improved PFS (arm B), with a modest trend for survival benefit (arm C) and increased toxicity reflective of known VEGF/PDGF inhibitory effects.

• MeSH
• aplikace orální MeSH
• dospělí MeSH
• fenylmočovinové sloučeniny aplikace a dávkování   škodlivé účinky   MeSH
• indazoly aplikace a dávkování   škodlivé účinky   MeSH
• Kaplanův-Meierův odhad MeSH
• karboplatina aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory plic farmakoterapie   mortalita   MeSH
• nemalobuněčný karcinom plic farmakoterapie   mortalita   MeSH
• paclitaxel aplikace a dávkování   MeSH
• přežití bez známek nemoci MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• receptory růstového faktoru odvozeného z trombocytů antagonisté a inhibitory   MeSH
• rozvrh dávkování léků MeSH
• senioři MeSH
• vaskulární endoteliální růstový faktor A antagonisté a inhibitory   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

CONTEXT: The Bruton tyrosine kinase (BTK) inhibitor, zanubrutinib, was designed for high BTK specificity and minimal toxicity. SEQUOIA (NCT03336333) is a global, open-label, randomized phase 3 study in treatment-naïve patients with CLL/SLL without del(17p) who were unsuitable for fludarabine/cyclophosphamide/rituximab. DESIGN: Patients were randomized to receive zanubrutinib (160 mg twice daily) or bendamustine (day 1-2: 90 mg/m2) and rituximab (cycle 1: 375 mg/m2; cycles 2-6: 500 mg/m2); stratification factors were age (<65 years vs ≥65 years), Binet Stage, IGHV mutation, and geographic region. MAIN OUTCOME MEASURES: Primary endpoint was an independent review committee (IRC)-assessed progression-free survival (PFS). Secondary endpoints included investigator-assessed (INV) PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: From October 31, 2017, to July 22, 2019, 479 patients were enrolled (zanubrutinib=241; BR=238). Baseline characteristics (zanubrutinib vs BR): median age, 70.0 years versus 70.0 years; unmutated IGHV, 53.4% versus 52.4%; del(11q), 17.8% versus 19.3%. With median follow-up of 26.2 months, PFS was significantly prolonged with zanubrutinib by IRC (HR 0.42; 2-sided P<.0001) and INV (HR 0.42; 2-sided P=.0001). Zanubrutinib treatment benefit occurred across age, Binet stage, bulky disease, del(11q) status, and unmutated IGHV (HR 0.24; 2-sided P<.0001), but not mutated IGHV (HR 0.67; 2-sided P=.1858). For zanubrutinib versus BR, 24-month PFS-IRC=85.5% versus 69.5%; ORR-IRC=94.6% versus 85.3%; complete response rate=6.6% versus 15.1%; ORR-INV=97.5% versus 88.7%; and 24-month OS=94.3% versus 94.6%. Select adverse event (AE) rates (zanubrutinib vs BR): atrial fibrillation (3.3% vs 2.6%), bleeding (45.0% vs 11.0%), hypertension (14.2% vs 10.6%), infection (62.1% vs 55.9%), and neutropenia (15.8% vs 56.8%). Treatment discontinuation due to AEs (zanubrutinib vs BR)=20 patients (8.3%) versus 31 patients (13.7%); AEs leading to death=11 patients (4.6%) versus 11 patients (4.8%). No sudden deaths occurred. CONCLUSIONS: In summary, zanubrutinib significantly improved PFS-IRC versus BR and was well tolerated, supporting the potential utility of frontline zanubrutinib in treatment-naïve CLL/SLL.

• MeSH
• B-buněčný lymfom * farmakoterapie   MeSH
• bendamustin hydrochlorid terapeutické užití   MeSH
• chronická lymfatická leukemie * farmakoterapie   patologie   MeSH
• cyklofosfamid terapeutické užití   MeSH
• inhibitory proteinkinas * škodlivé účinky   MeSH
• lidé MeSH
• piperidiny škodlivé účinky   MeSH
• proteinkinasa BTK MeSH
• protokoly protinádorové kombinované chemoterapie * škodlivé účinky   MeSH
• pyrazoly škodlivé účinky   MeSH
• pyrimidiny škodlivé účinky   MeSH
• rituximab terapeutické užití   MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Platinum-resistant ovarian cancer patients have a poor prognosis and few treatment options are available. Preclinical and clinical data demonstrated that the combination of poly-ADP ribose polymerase inhibitors with immune checkpoint inhibitors could have a synergistic antitumor activity in this setting of patients. PRIMARY OBJECTIVE: The primary objective is to assess the efficacy of niraparib plus dostarlimab compared with chemotherapy in recurrent ovarian cancer patients not suitable for platinum treatment. STUDY HYPOTHESIS: This trial will assess the hypothesis that niraparib plus dostarlimab therapy is effective to increase overall survival, progression-free survival, and time to first subsequent therapy respect to chemotherapy alone, with an acceptable toxicity profile. TRIAL DESIGN: This is a phase III, multicenter trial, where recurrent ovarian cancer patients not eligible for platinum re-treatment will be randomized 1:1 to receive niraparib plus dostarlimab vs physician's choice chemotherapy until disease progression, intolerable toxicity, or withdrawal of patient consent. The study will be performed according to European Network for Gynaecological Oncological Trial groups (ENGOT) model B and patients will be recruited from 40 sites across MITO, CEEGOG, GINECO, HeCOG, MANGO, and NOGGO groups. MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible patients must have recurrent epithelial ovarian cancer not eligible for platinum retreatment. Patients who received previous treatment with poly-ADP ribose polymerase inhibitors and/or immune checkpoint inhibitors will be eligible. No more than two prior lines of treatment are allowed. PRIMARY ENDPOINT: The primary endpoint is overall survival defined as the time from the randomization to the date of death by any cause. SAMPLE SIZE: 427 patients will be randomized. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: June 2024 TRIAL REGISTRATION NUMBER: NCT04679064.

• MeSH
• chemorezistence MeSH
• humanizované monoklonální protilátky aplikace a dávkování   MeSH
• indazoly aplikace a dávkování   MeSH
• inhibitory kontrolních bodů aplikace a dávkování   MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   MeSH
• nádory vaječníků farmakoterapie   MeSH
• PARP inhibitory aplikace a dávkování   MeSH
• peritoneální nádory farmakoterapie   MeSH
• piperidiny aplikace a dávkování   MeSH
• protokoly protinádorové kombinované chemoterapie aplikace a dávkování   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

CONTEXT: CLL/SLL treatment has been transformed with Bruton tyrosine kinase inhibitors (BTKi) such as ibrutinib. Zanubrutinib, a next-generation BTKi, was designed to maximize BTK occupancy and minimize toxicity. ALPINE (NCT03734016) is a global, randomized, phase 3 study of zanubrutinib versus ibrutinib in patients with R/R CLL/SLL; presented here is a pre-planned interim analysis conducted ~12 months after 415 patients enrolled between November 5, 2018, and December 20, 2019. DESIGN: Patients were randomized 1:1 to zanubrutinib (160 mg twice daily) or ibrutinib (420 mg once daily) arms; stratification factors were age (<65 years vs ≥65 years), geographic region, refractory status, and del(17)p/TP53 mutation. MAIN OUTCOME MEASURES: Primary endpoint was investigator-assessed overall response rate (ORR) per 2008 IWCLL guidelines or Lugano criteria; the noninferiority of zanubrutinib-to-ibrutinib response ratio was evaluated at the noninferiority margin of 0.8558. If noninferiority was demonstrated, superiority of zanubrutinib versus ibrutinib in ORR was tested. RESULTS: Baseline characteristics (zanubrutinib versus ibrutinib): age ≥65 years: 62.3% versus 61.5%, male sex 68.6% versus 75%; >3 prior therapies: 7.2% versus 10.1%; del(17)p: 11.6% versus 12.5%; TP53 mutation without del(17)p: 8.2% versus 5.8%. With a median follow-up of 15 months, ORR was 78.3% versus 62.5% for zanubrutinib versus ibrutinib, respectively (2-sided P=0.0006, prespecified a=0.0099). ORR was higher for zanubrutinib in patients with del(11)q (83.6% vs 69.1%) and del(17)p (83.3% vs 53.8%); zanubrutinib had higher overall 12-month progression-free survival (PFS; 94.9% vs 84.0%) and overall survival (97.0% vs 92.7%). Significantly fewer patients had atrial fibrillation/flutter (AF) with zanubrutinib versus ibrutinib (2.5% vs 10.1%, 2-sided P=0.0014, prespecified a=0.0099). Zanubrutinib had lower rates of major bleeding (2.9% vs 3.9%), adverse events leading to discontinuation (7.8% vs 13.0%), and death (3.9% vs 5.8%). Zanubrutinib had a higher neutropenia rate (28.4% vs 21.7%) while grade ≥3 infections (12.7% vs 17.9%) were lower. CONCLUSIONS: In summary, this interim analysis showed zanubrutinib had a superior ORR, improved PFS, and lower AF rate compared to ibrutinib.

• MeSH
• adenin analogy a deriváty   MeSH
• B-buněčný lymfom * farmakoterapie   genetika   MeSH
• chronická lymfatická leukemie * farmakoterapie   genetika   MeSH
• inhibitory proteinkinas * škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• piperidiny škodlivé účinky   MeSH
• pyrazoly škodlivé účinky   MeSH
• pyrimidiny škodlivé účinky   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• randomizované kontrolované studie MeSH

PURPOSE: Ibrutinib has shown activity in non-germinal center B-cell diffuse large B-cell lymphoma (DLBCL). This double-blind phase III study evaluated ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in untreated non-germinal center B-cell DLBCL. PATIENTS AND METHODS: Patients were randomly assigned at a one-to-one ratio to ibrutinib (560 mg per day orally) plus R-CHOP or placebo plus R-CHOP. The primary end point was event-free survival (EFS) in the intent-to-treat (ITT) population and the activated B-cell (ABC) DLBCL subgroup. Secondary end points included progression-free survival (PFS), overall survival (OS), and safety. RESULTS: A total of 838 patients were randomly assigned to ibrutinib plus R-CHOP (n = 419) or placebo plus R-CHOP (n = 419). Median age was 62.0 years; 75.9% of evaluable patients had ABC subtype disease, and baseline characteristics were balanced. Ibrutinib plus R-CHOP did not improve EFS in the ITT (hazard ratio [HR], 0.934) or ABC (HR, 0.949) population. A preplanned analysis showed a significant interaction between treatment and age. In patients age younger than 60 years, ibrutinib plus R-CHOP improved EFS (HR, 0.579), PFS (HR, 0.556), and OS (HR, 0.330) and slightly increased serious adverse events (35.7% v 28.6%), but the proportion of patients receiving at least six cycles of R-CHOP was similar between treatment arms (92.9% v 93.0%). In patients age 60 years or older, ibrutinib plus R-CHOP worsened EFS, PFS, and OS, increased serious adverse events (63.4% v 38.2%), and decreased the proportion of patients receiving at least six cycles of R-CHOP (73.7% v 88.8%). CONCLUSION: The study did not meet its primary end point in the ITT or ABC population. However, in patients age younger than 60 years, ibrutinib plus R-CHOP improved EFS, PFS, and OS with manageable safety. In patients age 60 years or older, ibrutinib plus R-CHOP was associated with increased toxicity, leading to compromised R-CHOP administration and worse outcomes. Further investigation is warranted.

• MeSH
• cyklofosfamid aplikace a dávkování   škodlivé účinky   MeSH
• difúzní velkobuněčný B-lymfom farmakoterapie   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• doxorubicin aplikace a dávkování   škodlivé účinky   MeSH
• dvojitá slepá metoda MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• mladý dospělý MeSH
• placebo MeSH
• prednison aplikace a dávkování   škodlivé účinky   MeSH
• protokoly protinádorové kombinované chemoterapie aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• pyrazoly aplikace a dávkování   škodlivé účinky   MeSH
• pyrimidiny aplikace a dávkování   škodlivé účinky   MeSH
• rituximab aplikace a dávkování   škodlivé účinky   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vinkristin aplikace a dávkování   škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Research Support, N.I.H., Extramural MeSH

OBJECTIVE: The objective of this study was to investigate whether diacerein has comparable efficacy with celecoxib in pain reduction for treatment in symptomatic knee OA patients. METHODS: This randomized double-blind multicentre non-inferiority trial evaluated diacerein vs celecoxib treatment in patients with Kellgren-Lawrence grade 2-3 and pain scoring ≥4 (10-cm VAS). Patients were randomized to 6 months of treatment with diacerein 50 mg (n = 187) once daily for 1 month and twice daily thereafter, or celecoxib 200 mg (n = 193) once daily. The primary outcome was the change in WOMAC pain score (0-50 cm) at 6 months, and the secondary outcomes were WOMAC sub-scores, VAS pain score, and the OMERACT-OARSI responder rate. RESULTS: In the per protocol population, the adjusted mean change from baseline in the WOMAC pain score was -11.1 ( 0.9) with diacerein (n = 140) and -11.8 (0.9) with celecoxib (n = 148). The intergroup difference was 0.7 (95% CI: -1.8, 3.2; P = 0.597), meeting the non-inferiority margin. Supportive analysis of the intention-to-treat population gave similar results. Other outcomes showed no significant difference between treatment groups. The incidence of treatment-related adverse events was low and balanced between groups, but a greater incidence of diarrhoea occurred with diacerein (10.2% vs 3.7%). Diarrhoea was considered mild-to-moderate in all but one case with complete resolution. CONCLUSIONS: Diacerein was non-inferior to celecoxib in reducing knee OA pain and improving physical function. Diacerein also demonstrated a good safety profile. TRIAL REGISTRATION: A multicentre study on the effect of DIacerein on Structure and Symptoms vs Celecoxib in Osteoarthritis is a National Institutes of Health (NCT02688400) and European Clinical Trial Database (2015-002933-23) registered phase III (Canada) or IV (Europe) study.

• MeSH
• anthrachinony terapeutické užití   MeSH
• antiflogistika nesteroidní terapeutické užití   MeSH
• artralgie farmakoterapie   MeSH
• artróza kolenních kloubů farmakoterapie   MeSH
• celekoxib terapeutické užití   MeSH
• dvojitá slepá metoda MeSH
• lidé středního věku MeSH
• lidé MeSH
• měření bolesti MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnocení ekvivalence MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Bruton tyrosine kinase (BTK) inhibition is an effective treatment approach for patients with Waldenström macroglobulinemia (WM). The phase 3 ASPEN study compared the efficacy and safety of ibrutinib, a first-generation BTK inhibitor, with zanubrutinib, a novel highly selective BTK inhibitor, in patients with WM. Patients with MYD88L265P disease were randomly assigned 1:1 to treatment with ibrutinib or zanubrutinib. The primary end point was the proportion of patients achieving a complete response (CR) or a very good partial response (VGPR) by independent review. Key secondary end points included major response rate (MRR), progression-free survival (PFS), duration of response (DOR), disease burden, and safety. A total of 201 patients were randomized, and 199 received ≥1 dose of study treatment. No patient achieved a CR. Twenty-nine (28%) zanubrutinib patients and 19 (19%) ibrutinib patients achieved a VGPR, a nonstatistically significant difference (P = .09). MRRs were 77% and 78%, respectively. Median DOR and PFS were not reached; 84% and 85% of ibrutinib and zanubrutinib patients were progression free at 18 months. Atrial fibrillation, contusion, diarrhea, peripheral edema, hemorrhage, muscle spasms, and pneumonia, as well as adverse events leading to treatment discontinuation, were less common among zanubrutinib recipients. Incidence of neutropenia was higher with zanubrutinib, although grade ≥3 infection rates were similar in both arms (1.2 and 1.1 events per 100 person-months). These results demonstrate that zanubrutinib and ibrutinib are highly effective in the treatment of WM, but zanubrutinib treatment was associated with a trend toward better response quality and less toxicity, particularly cardiovascular toxicity.

• MeSH
• adenin aplikace a dávkování   analogy a deriváty   MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• následné studie MeSH
• piperidiny aplikace a dávkování   MeSH
• prognóza MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• pyrazoly aplikace a dávkování   MeSH
• pyrimidiny aplikace a dávkování   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Waldenströmova makroglobulinemie farmakoterapie   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH