Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial.
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SUBMITTER: Faivre-Finn C
PROVIDER: S-EPMC5555437 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe clinical significance of circulating tumour cells (CTCs) in limited-stage small-cell lung cancer (LS-SCLC) is not well defined. We report a planned exploratory analysis of the prevalence and prognostic value of CTCs in LS-SCLC patients enrolled within the phase III randomised CONVERT (concurrent once-daily versus twice-daily chemoradiotherapy) trial.Patients and methodsBaseline blood samples were enumerated for CTCs using CellSearch in 75 patients with LS-SCLC who were enrolled in the CONVERT trial and randomised between twice- and once-daily concurrent chemoradiation. Standard statistical methods were used for correlations of CTCs with clinical factors. Log-rank test and Cox regression analyses were applied to establish the associations of 2, 15 and 50 CTC thresholds with progression-free survival (PFS) and overall survival (OS). An optimal CTC count threshold for LS-SCLC was established.ResultsCTCs were detected in 60% (45/75) of patients (range 0-3750). CTC count thresholds of 2, 15 and 50 CTCs all significantly correlate with PFS and OS. An optimal CTC count threshold in LS-SCLC was established at 15 CTCs, defining 'favourable' and 'unfavourable' prognostic risk groups. The median OS in <15 versus ≥15 CTCs was 26.7 versus 5.9 m (P = 0.001). The presence of ≥15 CTCs at baseline independently predicted ≤1 year survival in 70% and ≤2 years survival in 100% of patients.ConclusionWe report the prognostic value of baseline CTC count in an exclusive LS-SCLC population at thresholds of 2, 15 and 50 CTCs. Specific to LS-SCLC, ≥15 CTCs was associated with worse PFS and OS independent of all other factors and predicted ≤2 years survival. These results may improve disease stratification in future clinical trial designs and aid clinical decision making.Trial registrationClinicalTrials.gov identifier: NCT00433563.
| S-EPMC6637373 | biostudies-literature
Project description:Background: Currently, the accepted standard management of limited-stage small cell lung cancer (SCLC) is concurrent chemoradiotherapy (CCRT), but the frequency of radiotherapy is controversial. Therefore, this meta-analysis, which compared the efficacy and toxicity between twice-daily (BID) and once-daily (OD) CCRT, was performed to help clinicians make better decisions. Methods: Relevant randomized controlled trials (RCTs) were collected by searching the PubMed, Ovid MEDLINE, Embase, ScienceDirect, Web of Science, the Cochrane Library, Scopus and Google Scholar databases to assess antitumor effects (overall survival, OS; progression-free survival, PFS; overall response rate, ORR) and toxicity (adverse effects, AEs). Results: We screened 1499 articles and included 5 RCTs including 1421 patients. We found that BID CCRT improved OS (hazard ratio, HR = 0.88, 95% confidence interval, CI 0.78-0.99, p = 0.03), the 1-year OS rate (OSR-1y, risk ratio, RR = 1.07, 95%CI 1.01-1.13, p = 0.03), and OSR-4y (RR = 1.22, 95%CI 1.03-1.43, p = 0.02), with better trends in OSR-2y, OSR-3y, and OSR-5y, compared to OD CCRT. In addition, BID CCRT had a higher complete response (CR, RR = 1.31, 95%CI 1.01-1.70, p = 0.04) than OD CCRT. PFS (HR = 0.92, 95%CI 0.79-1.07, p = 0.29), annual PFS rate, ORR (RR = 0.99, 95%CI 0.93-1.05, p = 0.72), and AEs for all grades (RR = 1.00, 95%CI 0.98-1.01, p = 0.57), and grades 3-5 (RR = 1.02, 95%CI 0.95-1.09, p = 0.60) were similar between the two arms. Conclusions: BID CCRT appears to be better than OD CCRT for limited-stage SCLC, with better antitumor effects (OS, OSR, and CR) and similar AEs. However, the high levels of AEs in both arms should be taken as a sign of caution. More large sample and high-quality RCTs need to be conducted to confirm our conclusions.
| S-EPMC6960125 | biostudies-literature
Project description:Approximately 20% to 40% of patients with gastroesophageal reflux disease (GERD) are refractory to standard-dose proton-pump inhibitor (PPI) treatment.We compared the efficacy and quality-of-life effects of 20 mg once daily (QD) versus 10 mg twice daily (BID) rabeprazole (RPZ) in patients with refractory GERD-related symptoms and sleep disturbances.This multicenter, prospective, randomized, open-label study included patients in whom PPI treatment >4 weeks was ineffective. According to the Global Overall Symptom (GOS) scale, PPI-refractory GERD was defined as ?1 category with >3 points among 10 specific upper gastrointestinal symptoms. Seventy-eight patients were randomly assigned to 20 mg QD and 10 mg BID RPZ groups for 8 weeks. Efficacy was evaluated using self-reported questionnaires, including the GOS scale and Pittsburg Sleep Quality Index (PSQI), whereas quality of life was assessed using the Short-Form 8 Health Survey (SF-8), at 4 and 8 weeks. Patients showing improvement at 8 weeks received follow-up every 4 to 8 weeks.GOS scale scores were significantly improved at 8 weeks in both groups, with no significant intergroup differences. Although SF-8 scores showed an increasing trend over 8 weeks in both groups, the physical component summaries in the 10 mg BID group significantly improved. The mental component summaries clearly improved in the 10 mg BID group. Of the 74 cases (4 missing), 51 (68.9%) had PSQI scores ?5.5. PSQI scores remained unchanged during follow-up in both groups. The recurrence rate was not significantly different (46.1% vs 47.1% in the 20 mg QD and 10 mg BID groups, respectively) during the follow-up period at median (interquartile range) 24.0 (30.5) months.In patients with refractory GERD, there was no significant difference in GOS scale score, PSQI, or recurrence rate between the groups. With regard to subscores of the SF-8, the 10 mg BID group might be potentially effective.
| S-EPMC5200872 | biostudies-other
Project description:This study was designed to compare toxicities, disease control, and survival outcomes for limited disease small-cell lung cancer (LD-SCLC) treated with once daily (QD) versus twice daily (BID) radiotherapy.All of the patients received four to six cycles of platinum plus etoposide. In the QD group, irradiation was given via conventional radiotherapy with a dose of 60?Gy at 2?Gy per once-daily fraction. In the BID group, the dose was 45?Gy at 1.5?Gy per twice-daily fraction.Data from a total of 143 LD-SCLC patients treated at the Shandong Cancer Hospital & Institute were retrospectively analyzed. Statistically significant differences were found in the rates of both grade 2 or higher esophagitis (P = 0.036) and pneumonitis (P = 0.043) between QD and BID groups, respectively. Grade 3 esophagitis occurred in 6% of patients receiving QD and 19% of those receiving BID therapy. The median overall survival (OS) of all patients was 30.4 months: 29.5 months for QD therapy, and 31.4 months for BID therapy. The two-year OS rate was 43.3% for QD therapy, and 48.8% for BID therapy. The two-year locoregional recurrence-free survival (LRFS) rate was 45% versus 63.4% for the QD group versus the BID group, respectively.Pneumonitis was more common in the QD group, and esophagitis was more common in the BID group. Although there were no significant differences in OS and LRFS between the QD and BID groups, there was a trend toward improved local control in the BID group.
| S-EPMC4567011 | biostudies-other
Project description:To compare efficacy and safety of lixisenatide once daily versus exenatide twice daily in type 2 diabetes inadequately controlled with metformin.Adults with diabetes inadequately controlled (HbA1c 7-10%) with metformin were randomized to lixisenatide 20 ?g once daily (n=318) or exenatide 10 ?g twice daily (n=316) in a 24-week (main period), open-label, parallel-group, multicenter study. The primary objective was a noninferiority assessment of lixisenatide versus exenatide in HbA1c change from baseline to week 24.Lixisenatide once daily demonstrated noninferiority in HbA1c reduction versus exenatide twice daily. The least squares mean change was -0.79% (mean decrease 7.97 to 7.17%) for lixisenatide versus -0.96% (mean decrease 7.96 to 7.01%) for exenatide, and treatment difference was 0.17% (95% CI, 0.033-0.297), meeting a predefined noninferiority upper CI margin of 0.4%. Responder rate (HbA1c<7.0%) and improvements in fasting plasma glucose were comparable. Both agents induced weight loss (from 94.5 to 91.7 kg and from 96.7 to 92.9 kg with lixisenatide and exenatide, respectively). Incidence of adverse events (AEs) was similar for lixisenatide and exenatide, as was incidence of serious AEs (2.8 and 2.2%, respectively). Discontinuations attributable to AEs occurred in 33 lixisenatide (10.4%) and 41 exenatide (13.0%) patients. In the lixisenatide group, fewer participants experienced symptomatic hypoglycemia (2.5 vs. 7.9%; P<0.05), with fewer gastrointestinal events (especially nausea; 24.5 vs. 35.1%; P<0.05).Add-on lixisenatide once daily in type 2 diabetes inadequately controlled with metformin demonstrated noninferior improvements in HbA1c, with slightly lower mean weight loss, lower incidence of hypoglycemia, and better gastrointestinal tolerability compared with exenatide twice daily.
| S-EPMC3781502 | biostudies-literature
Project description:Inhaled corticosteroids are the recommended first-line treatment for asthma but adherence to therapy is suboptimal. The objectives of this study were to compare the efficacy and safety of once-daily (OD) evening and twice-daily (BD) regimens of the novel inhaled corticosteroid fluticasone furoate (FF) in asthma patients.Patients with moderate asthma (age ? 12 years; pre-bronchodilator forced expiratory volume in 1 second (FEV1) 40-85% predicted; FEV1 reversibility of ? 12% and ? 200 ml) were randomized to FF or fluticasone propionate (FP) regimens in a double-blind, crossover study. Patients were not permitted to have used any ICS for ? 8 weeks prior to enrolment and subsequently received doses of FF or FP 200 ?g OD, FF or FP 100 ?g BD and matching placebo by inhalation for 28 days each. Primary endpoint was Day 28 evening pre-dose (trough) FEV1; non-inferiority of FF 200 ?g OD and FF 100 ?g BD was assessed, as was superiority of all active treatment relative to placebo. Adverse events (AEs) and 24-hour urinary cortisol excretion were assessed.The intent-to-treat population comprised 147 (FF) and 43 (FP) patients. On Day 28, pre-dose FEV1 showed FF 200 ?g OD to be non-inferior (pre-defined limit -110 ml) to FF 100 ?g BD (mean treatment difference 11 ml; 95% CI: -35 to +56 ml); all FF and FP regimens were significantly superior to placebo (p ? 0.02). AEs were similar to placebo; no serious AEs were reported. Urinary cortisol excretion at Day 28 for FF was lower than placebo (ratios: 200 ?g OD, 0.75; 100 ?g BD, 0.84; p ? 0.02).FF 200 ?g OD in the evening is an efficacious and well tolerated treatment for asthma patients and is not inferior to the same total BD dose.Clinicaltrials.gov; NCT00766090.
| S-EPMC3282675 | biostudies-literature
Project description:This open-label study aimed to compare once-daily and twice-daily pramipexole extended release (PER) treatment in Parkinson's disease (PD). PD patients on dopamine agonist therapy, but with unsatisfactory control, were enrolled. Existing agonist doses were switched into equivalent PER doses. Subjects were consecutively enrolled into either once-daily-first or twice-daily-first groups and received the prescribed amount in one or two, respectively, daily doses for 8 weeks. For the second period, subjects switched regimens in a crossover manner. The forty-four patients completed a questionnaire requesting preference during their last visit. We measured the UPDRS-III, Hoehn and Yahr stages (H&Y) in medication-on state, Parkinson's disease sleep scale (PDSS), and Epworth Sleepiness Scale. Eighteen patients preferred a twice-daily regimen, 12 preferred a once-daily regimen, and 14 had no preference. After the trial, 14 subjects wanted to be on a once-daily regimen, 25 chose a twice-daily regimen, and 5 wanted to maintain the prestudy regimen. Main reasons for choosing the twice-daily regimen were decreased off-duration, more tolerable off-symptoms, and psychological stability. The mean UPDRS-III, H&Y, and PDSS were not different. Daytime sleepiness was significantly high in the once-daily regimen, whereas nocturnal hallucinations were more common in the twice-daily. Multiple dosing should be considered if once-daily dosing is unsatisfactory. This study is registered as NCT01515774 at ClinicalTrials.gov.
| S-EPMC5318624 | biostudies-literature
Project description:ObjectiveInsulin icodec is a novel once-weekly basal insulin analog. This trial investigated the efficacy and safety of icodec using different once-weekly titration algorithms.Research design and methodsThis was a phase 2, randomized, open-label, 16-week, treat-to-target study. Insulin-naïve adults (n = 205) with type 2 diabetes and HbA1c 7-10% while treated with oral glucose-lowering medications initiated once-weekly icodec titrations A (prebreakfast self-measured blood glucose target 80-130 mg/dL; adjustment ±21 units/week; n = 51), B (80-130 mg/dL; ±28 units/week; n = 51), or C (70-108 mg/dL; ±28 units/week; n = 52), or once-daily insulin glargine U100 (IGlar U100) (80-130 mg/dL; ±4 units/day; n = 51), all titrated weekly. Percentage of time in range (TIR) (70-180 mg/dL) during weeks 15 and 16 was measured using continuous glucose monitoring.ResultsTIR improved from baseline (means: A, 57.0%; B, 55.2%; C, 51.0%; IGlar U100, 55.3%) to weeks 15 and 16 (estimated mean: A, 76.6%; B, 83.0%; C, 80.9%; IGlar U100, 75.9%). TIR was greater for titration B than for IGlar U100 (estimated treatment difference 7.08%-points; 95% CI 2.12 to 12.04%; P = 0.005). No unexpected safety signals were observed. Level 2 hypoglycemia (<54 mg/dL) was low in all groups (0.05, 0.15, 0.38, 0.00 events per patient-year of exposure for icodec titrations A, B, and C and IGlar U100, respectively), with no episodes of severe hypoglycemia.ConclusionsOnce-weekly icodec was efficacious and well tolerated across all three titration algorithms investigated. The results for icodec titration A (80-130 mg/dL; ±21 units/week) displayed the best balance between glycemic control and risk of hypoglycemia.
| S-EPMC8323172 | biostudies-literature
Project description:BackgroundAntiretroviral therapy (ART) adherence is critical for successful HIV treatment outcomes. Once-daily dosing could improve adherence. Plasma concentrations of once-daily vs twice-daily abacavir + lamivudine are bioequivalent in children, but no randomized trial has compared virological outcomes.MethodsChildren taking abacavir + lamivudine-containing first-line regimens twice daily for more than 36 weeks in the ARROW trial (NCT02028676, ISRCTN24791884) were randomized to continue twice-daily vs move to once-daily abacavir + lamivudine (open-label). Co-primary outcomes were viral load suppression at week 48 (12% noninferiority margin, measured retrospectively) and lamivudine or abacavir-related grade 3/4 adverse events.ResultsSix hundred and sixty-nine children (median 5 years, range 1-16) were randomized to twice daily (n = 333) vs once daily (n = 336) after median 1.8 years on twice-daily abacavir + lamivudine-containing first-line ART. Children were followed for median 114 weeks. At week 48, 242/331 (73%) twice daily vs 236/330 (72%) once daily had viral load less than 80 copies/ml [difference -1.6% (95% confidence interval -8.4,+5.2%) P = 0.65]; 79% twice daily vs 78% once daily had viral load less than 400 copies/ml (P = 0.76) (week 96 results similar). One grade 3/4 adverse event was judged uncertainly related to abacavir + lamivudine (hepatitis; once daily). At week 48, 9% twice daily vs 10% once daily reported missing one or more ART pills in the last 4 weeks (P = 0.74) and 8 vs 8% at week 96 (P = 0.90). Carers strongly preferred once-daily dosing. There was no difference between randomized groups in postbaseline drug-resistance mutations or drug-susceptibility; WHO 3/4 events; ART-modifying, grade 3/4 or serious adverse events; CD4% or weight-for-age/height-for-age (all P > 0.15).ConclusionOnce-daily abacavir + lamivudine was noninferior to twice daily in viral load suppression, with similar resistance, adherence, clinical, immunological and safety outcomes. Abacavir + lamivudine provides the first once-daily nucleoside backbone across childhood that can be used to simplify ART.
| S-EPMC6217915 | biostudies-literature
Project description:Momelotinib, a small-molecule inhibitor of Janus kinase 1 and Janus kinase 2, has demonstrated efficacy in myelofibrosis patients with 300 mg, once-daily dosing. This open-label, non-randomized, phase 1/2 study evaluated the safety and therapeutic benefit of momelotinib with twice-daily dosing. A total of 61 subjects with primary myelofibrosis or post-polycythemia vera/post-essential thrombocythemia myelofibrosis with intermediate- or high-risk disease received momelotinib. A phase 1 dose escalation identified 200 mg twice daily as the optimal dose to be expanded in phase 2. The most frequent adverse events were diarrhea (45.9%), peripheral neuropathy (44.3%), thrombocytopenia (39.3%), and dizziness (36.1%), the latter primarily due to a first-dose effect. The response assessment according to the 2006 International Working Group criteria (?8 weeks duration at any time point) demonstrated spleen response by palpation of 72% (36/50) and anemia response of 45% (18/40). Spleen response by magnetic resonance imaging obtained at 24 weeks was 45.8% (27/59) for all subjects and 54.0% (27/50) for those with palpable splenomegaly at baseline. The symptoms of myelofibrosis were improved in most subjects. Cytokine analysis showed a rapid decline in interleukin-6 with momelotinib treatment, and a slower reduction in other inflammatory cytokines. In the subgroup of subjects with the JAK2V617F mutation at baseline (n=41), momelotinib significantly reduced the allele burden by 21.1% (median) at 24 weeks. These results provide evidence of tolerability and a potential therapeutic activity of momelotinib for subjects that support further evaluation in ongoing, phase 3 randomized trials. (clinicaltrials. gov identifier:01423058).
| S-EPMC5210237 | biostudies-literature