scholarly journals The Efficacy and Safety of Bilastine in the Treatment of Perennial Allergic Rhinitis in Patients with Moderate and Severe Forms of the Disease. Comparison of bilastine 20 mg with desloratadine 5 mg Сергей

2019 ◽  
pp. 58-67
Author(s):  
S. Ryazantsev ◽  
I. Gogunska ◽  
I. Lymar ◽  
L. Romanyuk ◽  
B. Bil ◽  
...  
Keyword(s):  
Symptomatic Treatment ◽  
Phase Iii ◽  
Comparable Efficacy ◽  
Open Label ◽  
Prick Test ◽  
Treatment Groups ◽  
Persistent Symptoms ◽  
Parallel Group ◽  
Significant Difference ◽  
Rhino Conjunctivitis

Background: Bilastine is a new non-sedating H1 antihistamine approved for the symptomatic treatment of allergic rhinoconjunctivitis (ARC) and urticaria in adults and children over 12 years of age. In this paper, bilastine was compared with desloratadine in the treatment of various forms of allergic rhino-conjunctivitis classified according to the ARIA recommendations.Materials and Methods: This was an international, multi-centre, open-label, prospective randomized, parallel-group, phase III study which enrolled a total of 226 patients with ARC. The diagnosis of the allergic rhino-conjunctivitis was established on the basis of nasal and non-nasal symptoms and confirmed by the skin prick test. Patients were randomized to one of the two treatment groups: bilastine 20 mg daily or desloratadine 5 mg daily.Results: The results for the primary and secondary endpoints showed a comparable reduction in TSS, NSS, and NNSS from the baseline to the end of the treatment between the treatment groups, with slightly better effects for bilastine. Additional tests carried out in the subgroup of patients with moderate / severe persistent (MSP) ARC demonstrated comparable results for the bilastine and desloratadine groups regarding the mean change in TSS from the baseline until the 28th day, except for the sneezing score, for which bilastine showed the higher response (-1.60 ± 0.60 vs. -1.39 ± 0.63), and a statistically significant difference between the treatment groups regarding AUC for TSS ( -26.07 [95% CI: -48.6, -3.53] p = 0.024), NNSS (-10.51 [95% CI:-19.42, -1.59] p = 0.021), the sneezing score (-4.79 [95% CI:-9.06, -0.51] p = 0.028) and the ocular redness score (-5.50 [95% CI: -8.91, -2.08] p = 0.02).Conclusion: In general, bilastine and desloratadine showed a comparable efficacy profile in the treatment of ARC; however, the results obtained in the subgroup of patients with moderate / severe persistent symptoms indicate that bilastine has a stronger therapeutic effect 

Symptomatic Treatment With Lanreotide Microparticles in Inoperable Bowel Obstruction Resulting From Peritoneal Carcinomatosis: A Randomized, Double-Blind, Placebo-Controlled Phase III Study

2012 ◽  
Vol 30 (35) ◽  
pp. 4337-4343 ◽  
Author(s):  
Pascale Mariani ◽  
Joëlle Blumberg ◽  
Alain Landau ◽  
Daniela Lebrun-Jezekova ◽  
Estelle Botton ◽  
...  
Keyword(s):  
Peritoneal Carcinomatosis ◽  
Bowel Obstruction ◽  
Well Being ◽  
Symptomatic Treatment ◽  
Phase Iii ◽  
Primary Analysis ◽  
Open Label ◽  
Double Blind ◽  
Parallel Group ◽  
Intent To Treat

Purpose To investigate the somatostatin analog lanreotide as symptomatic treatment for inoperable bowel obstruction due to peritoneal carcinomatosis. Patients and Methods In all, 80 patients with peritoneal carcinomatosis, inoperable malignant digestive obstruction, and two or more vomiting episodes per day or nasogastric tube (NGT) who were previously treated with intravenous corticosteroids and proton pump inhibitors were randomly assigned to one 30-mg injection of lanreotide microparticles (n = 43) or placebo (n = 37) in a 10-day, double-blind, parallel-group phase. The primary end point was the proportion of patients responding on day 7 (one or fewer episodes of vomiting per day or no vomiting recurrence after NGT removal [for ≥ 3 consecutive days in both cases]). Vomiting frequency/NGT secretion volumes, nausea, abdominal pain, well-being, and safety were also assessed. Patients could then enter an open-label lanreotide-only phase. The study was conducted at 22 European hospitals. Results More patients receiving lanreotide than placebo were responders; this difference was not statistically significant for the intent-to-treat (ITT) population on the basis of diary cards (primary analysis; 41.9% [18 of 43] v 29.7% [11 of 37], respectively; odds ratio, 1.75; 95% CI, 0.68 to 4.49; P = .24) but was statistically significant for the corresponding supportive per protocol analysis (57.7% [15 of 26] v 30.4% [seven of 23]; P < .05) and ITT analysis, on the basis of investigators' assessments (50.0% [19 of 38] v 28.6% [10 of 35]; P < .05). Improvements in well-being were significantly greater with lanreotide on days 3, 6, and 7. No significant differences were observed for other secondary end points. Only two (mild/moderate) treatment-emergent adverse events were considered related to lanreotide. Conclusion These results show that lanreotide has some efficacy and is safe in the symptomatic treatment of patients with inoperable bowel obstruction due to peritoneal carcinomatosis.

ESPAC-3(v2): A multicenter, international, open-label, randomized, controlled phase III trial of adjuvant 5-fluorouracil/folinic acid (5-FU/FA) versus gemcitabine (GEM) in patients with resected pancreatic ductal adenocarcinoma

2009 ◽  
Vol 27 (18_suppl) ◽  
pp. LBA4505-LBA4505 ◽  
Author(s):  
J. Neoptolemos ◽  
M. Büchler ◽  
D. D. Stocken ◽  
P. Ghaneh ◽  
D. Smith ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Bolus Injection ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Open Label ◽  
Treatment Groups ◽  
Significant Difference

LBA4505 Background: Adjuvant 5-FU/FA (ESPAC-1 trial) and GEM (CONKO-001 trial) provide improved survival for patients with resected pancreatic cancer compared to no chemotherapy. The aim of the ESPAC-3 (v2) trial was to compare 5FU/FA vs GEM to identify if either adjuvant chemotherapy was associated with a significantly better survival. Methods: Patients with an R0/R1 resection for pancreatic ductal adenocarcinoma were randomized (stratified for resection margin status and country) <8 weeks of surgery to receive either 5FU/FA (FA, 20 mg/m2, iv bolus injection followed by 5-FU, 425 mg/m2, iv bolus injection given 1–5d every 28 days) or GEM (1,000mg/m2 iv infusion 1d, 8d and 15d every 4 weeks) for 6 months. The primary outcome measure was overall survival; the secondary measures were toxicity, progression free survival and quality of life. 1,030 patients were needed to detect a 10% difference in 2-year survival rates with 90% power. Results: 1,088 patients from 16 countries were randomized from July 2000 to Jan 2007 (5FU/FA = 551, GEM = 537). Median (range) age was 63 (31–85) years; 598 (55%) were men. Median tumor size was 30 (20–350) mm; 384 (35%) were R1 resections; 777 (72%) were node positive; and 263 (25%) were poorly differentiated tumors. Final analysis was carried out on an intention to treat basis with a minimum of 2 years follow-up after 753 (69%) patients had died. Median (IQR) follow-up of 335 alive patients was 34.2 (27.1–43.4) months, equal across treatment groups. Median survival from resection of patients treated with 5FU/FA was 23.0 (95% CI: 21.1, 25.0) months and for patients treated with GEM this was 23.6 (95%CI: 21.4, 26.4) months. Log-rank analysis revealed no statistically significant difference in survival estimates between the treatment groups (c2LR=0.7, p=0.39, HRGEM=0.94 (95%CI: 0.81, 1.08)). There was no significant difference in the effect of treatment across subgroups according to R status (test of heterogeneity c21=0.3, p=0.56). Conclusions: This is the largest adjuvant trial ever conducted for pancreatic ductal adenocarcinoma and showed no significant difference in survival between adjuvant 5FU/FA and adjuvant GEM. [Table: see text]

scholarly journals MLTI-14. A SYSTEMATIC REVIEW OF TREATMENT PARADIGMS FOR PATIENTS WITH BREAST CANCER AND ONE OR MORE BRAIN METASTASES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i17-i17
Author(s):  
Yosef Ellenbogen ◽  
Karanbir Brar ◽  
Nebras Warsi ◽  
Jetan Badhiwala ◽  
Alireza Mansouri
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Adverse Events ◽  
Brain Metastases ◽  
Treatment Options ◽  
Inclusion Criteria ◽  
Open Label ◽  
Treatment Groups ◽  
Molecular Features ◽  
Significant Difference

Abstract BACKGROUND: Upwards of 50% of patients with advanced breast cancer are diagnosed with brain metastases (BM). Treatment options for these patients have been rapidly evolving due to increased understanding of the tumor pathophysiology and its genetic underpinnings. This systematic review of randomized controlled trials (RCTs) aims to clarify the evidence guiding the treatment of brain metastases from breast cancer. METHODS: MEDLINE, EMBASE, Cochrane Controlled Register of Trials, ClincialTrials.gov, and Web of Science were searched from inception to October 2018 for RCTs comparing treatments for breast cancer BM. We screened studies, extracted data, and assessed risk of bias independently and in duplicate. Outcomes assessed were overall survival (OS), progression-free survival (PFS), and adverse events (Grade 3+). RESULTS: Among 3188 abstracts, only 3 RCTs (N=412; mean sample size per group N=54.7) meeting inclusion criteria were identified. The studies were phase II or III open-label parallel superiority trials. Inclusion criteria among these trials consisted of age &gt;18 with radiologic evidence of &gt;1 BM. Exclusion criteria consisted of poor-performance functional status (ECOG &gt;2 or KPS &lt; 70). The treatment groups included whole-brain radiation therapy (WBRT) vs WBRT + Temozolomide, WBRT vs WBRT + Efaproxiral, and Afatinib vs Vinorelbine vs investigators’ choice (86% of these patients received WBRT or SRS prior to study enrolment). While two trials found no significant difference in OS, one trial found significant improvement in OS with Efaproxiral in addition to WBRT compared to WBRT alone (HR 0.52; 95%CI 0.332–0.816). No significant differences were found with PFS or rate of adverse events amongst treatment groups. CONCLUSION: Considering the high prevalence of breast cancer BM and our improved understanding of genomic/molecular features of these tumors, a greater number of RCTs dedicated at this disease are needed.

Bendamustine in the Treatment of Chronic Lymphocytic Leukemia -Consistent Superiority Over Chlorambucil in Elderly Patients and Across Clinically Defined Risk Groups.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2367-2367 ◽  
Author(s):  
Wolfgang Ulrich Knauf ◽  
Toshko Lissitchkov ◽  
Ali Aldaoud ◽  
Anna Liberati ◽  
Javier Loscertales ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Remission Rate ◽  
Risk Groups ◽  
The Elderly ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Response To Treatment ◽  
Open Label ◽  
Significant Difference ◽  
Binet Stage

Abstract Abstract 2367 Poster Board II-344 Introduction: Bendamustine is a purine analog/alkylator hybrid agent with a unique mechanism of action, which has shown good clinical efficacy and acceptable tolerability in various hematological malignancies. Chronic lymphocytic leukemia (CLL) is a disease of the elderly, and presents with a variety of clinical characteristics which influence the prognosis. We analyzed tolerability and efficacy of bendamustine (BEN) in comparison to chlorambucil (CLB) in clinical risk groups defined by age and specific indicators of disease activity. Patients and Methods: The efficacy and safety of BEN and CLB have been compared in a randomized, open-label, multicenter, phase III trial in patients with previously untreated advanced (Binet stage B/C) CLL. Patients were randomized to receive BEN (100 mg/m2 on days 1 + 2) or CLB (0.8 mg/kg on days 1 and 15) for up to 6 treatment cycles. The primary endpoints were overall remission rate (ORR), which was defined as complete or partial response, and progression-free survival (PFS). Secondary endpoints included overall survival (OS) and safety. The response to treatment was evaluated by a blinded Independent Response Assessment Committee. Results: A total of 319 patients were randomized (162 bendamustine, 157 chlorambucil), of whom all were included in the efficacy analysis, while 312 were evaluable for safety. Median age was 64 years (35 to 78). The median number of treatment cycles was 6 in both study arms, regardless of an age above or below 65 years. The median observation time was 35 months. ORR was significantly higher with BEN than with CLB (68% versus 31%, P<0.0001). The median PFS was 21.6 months with BEN and 8.3 months with CLB (P<0.0001). So far, there is no difference in OS (median not reached with BEN versus 65.4 months with CLB; p = 0.16). No significant difference in the remission rates became apparent when comparing patients below and above the age of 65 years (ORR 71.6 % versus 63.5 % with BEN, p>0.3; and 28.4 % versus 32.5 % with CLB, p>0.6). PFS was not influenced by age above 65 years, stage of disease (Binet stage B versus C), or elevated LDH. However, patients without B symptoms had a longer median PFS with BEN than those patients with B symptoms (30.4 months versus 17.7 months; p<0.0001), whereas median PFS was not affected by the presence of B symptoms in patients with CLB (8.9 months in both patient groups). Conclusion: This study has shown that bendamustine offers significantly greater efficacy than chlorambucil in the elderly and across clinically defined major risk groups, even in the presence of B symptoms. BEN should be considered as first-line chemotherapy for patients with advanced CLL. Disclosures: Knauf: mundipharma: Consultancy, Honoraria; cephalon: Consultancy, Honoraria. Klein:mundipharma: Consultancy, Honoraria. Merkle:mundipharma: Consultancy, Honoraria. Montillo:mundipharma Italy: Consultancy, Research Funding.

Ibandronate reduces radiotherapy-resistant metastatic bone pain in patients with solid tumors: A comparison of i.v. and oral formulations

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19517-19517
Author(s):  
K. Mystakidou ◽  
E. Stathopoulou ◽  
E. Parpa ◽  
I. Hatzipli ◽  
N. Touroutoglou ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Bone Pain ◽  
Progressive Disease ◽  
Bone Lesion ◽  
Phase Iii ◽  
Comparable Efficacy ◽  
Primary Tumor Site ◽  
Significant Difference ◽  
Analgesic Use ◽  
Renal Safety

19517 Background: Bisphosphonates are used to treat metastatic bone disease (MBD). However, some bisphosphonates are associated with renal toxicity. Ibandronate (IA) is a single-nitrogen, noncyclic bisphosphonate with a renal safety profile similar to placebo in phase III trials. This study compares the effects of i.v. IA 6mg and oral IA 50mg on bone pain, analgesic intake and renal safety. Methods: Recruited patients fulfilled the following criteria: age ≥18, solid tumors with at least one bone lesion, normal renal (serum creatinine ≤1.5mg/dL) and hepatic function, WHO performance status 0, I or II, life expectancy ≥6 months, normal serum calcium or asymptomatic hypercalcemia. Patients were excluded if they were pregnant or lactating, taking nephrotoxic drugs or osteoclast activity modulators. Eligible patients (n=52) were recruited for a two-arm study, with 26 patients per group treated over 6 months. Groups were matched for age, gender, weight, height, blood pressure, site of primary tumor, site and number of bone metastases and number of irradiated sites. Intravenous IA 6mg was administered over 15 minutes every 4 weeks. Oral IA 50mg was administered as a single, daily tablet before breakfast. Studies were ceased on occurrence of new bone events. Primary endpoint was reduction in bone pain and reduced analgesic use. Results: There were no significant differences in patient demographics between the two treatment arms. The percentage of patients receiving i.v. IA that achieved stable or progressive disease was 15.4%; those receiving oral IA attained 11.5% stable or progressive disease. Pain (Brief Pain Inventory questionnaire) and analgesic intake were assessed at baseline, 3 and 6 months. Both i.v. and oral IA caused a significant and sustainable decrease in each of the pain indices (p<0.0005) with no significant difference between i.v. and oral groups. Both i.v. and oral IA treatment led to a trend in decrease of analgesic use. Conclusions: Oral and i.v. ibandronate have comparable efficacy for palliation of bone pain in MBD patients. No significant financial relationships to disclose.

Neoadjuvant therapy for localized gastrointestinal stromal tumors (GISTs): A propensity score weighted analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e23516-e23516
Author(s):  
Kathryn E. Marqueen ◽  
Erin Moshier ◽  
Michael Buckstein ◽  
Celina Ang
Keyword(s):  
Overall Survival ◽  
Logistic Regression ◽  
Propensity Score ◽  
Survival Benefit ◽  
Postoperative Mortality ◽  
Phase Iii ◽  
R0 Resection ◽  
Treatment Groups ◽  
Significant Difference ◽  
The Impact

e23516 Background: Retrospective and single-arm prospective studies have reported clinical benefit associated with receipt of neoadjuvant imatinib for GISTs. In the absence of randomized phase III data, the impact of neoadjuvant systemic therapy (NAT) on survival, in comparison to upfront resection, remains unknown. Methods: We identified N = 14,402 patients with complete clinical, demographic, treatment and pathologic data within the National Cancer Database (2004-2016) who underwent resection of localized GIST of the stomach, esophagus, small bowel, and colorectum, with or without ≥3 months of NAT. Inverse probability of treatment weighting (IPTW) was used to adjust for covariable imbalance among treatment groups, with the propensity score estimated by logistic regression. The effect of NAT on overall survival was estimated with a weighted time-dependent Cox proportional hazards model. A weighted logistic regression was used to estimate the effect of NAT on 90-day postoperative mortality and R0 resection. Results: 759 (5.3%) patients received NAT followed by resection, compared to 13,643 (94.7%) who underwent upfront resection. Median length of NAT was 6.3 months. 53% of NAT patients were male vs. 49% of UR patients, 68% vs. 66% had primary gastric GIST, and 73% vs 49% were high risk. Patients receiving NAT had larger tumors (p < 0.001) and higher mitotic index (p = 0.003). There was a significant survival benefit associated with receipt of NAT (table). 90-day postoperative mortality rate was 3/759 (0.4%) among NAT patients vs. 307/13,643 (2.3%) UR patients. Receipt of NAT was significantly associated with lower odds of 90-day postoperative mortality (table). Of the 13,562 patients with information on margin status, the R0 resection rate was 635/716 (88.7%) for the neoadjuvant group vs. 11,823/12,846 (92%), with no significant difference between treatment groups (table). Conclusions: After adjustment for imbalance in prognostic and demographic factors, this analysis demonstrates that receipt of NAT for localized GIST is associated with a modest overall survival benefit. Although NAT patients had higher risk features, NAT was associated with a lower risk of 90-day postoperative mortality, with no difference in likelihood of achieving an R0 resection. [Table: see text]

Obesity Does Not Alter the Pharmacokinetics of Drotrecogin Alfa (Activated) in Severe Sepsis

2005 ◽  
Vol 39 (2) ◽  
pp. 262-267 ◽  
Author(s):  
Howard Levy ◽  
David Small ◽  
Darell E Heiselman ◽  
Richard Riker ◽  
Jay Steingrub ◽  
...  
Keyword(s):  
Body Weight ◽  
Severe Sepsis ◽  
Actual Body ◽  
Drotrecogin Alfa ◽  
Phase Iii ◽  
Actual Body Weight ◽  
Open Label ◽  
Risk Of Death ◽  
Drotrecogin Alfa Activated ◽  
Significant Difference

BACKGROUND: Drotrecogin alfa (activated) [DrotAA] is approved for the reduction of mortality in adults with severe sepsis (sepsis with acute organ dysfunction) and high risk of death. Patients whose actual body weight was >135 kg were excluded from the Phase III PROWESS trial. OBJECTIVE: To compare exposure to DrotAA in patients with severe sepsis weighing >135 kg with those weighing ⩽135 kg in an open-label, Phase IV trial, and quantify the elimination half-life (t1/2) of DrotAA in these patients. METHODS: PROWESS inclusion/exclusion criteria were used, except that patients >135 kg were enrolled. Blood samples were collected for steady-state plasma concentration (Css) analysis of activated protein C once each day and for t1/2 analysis after infusion. Weight-normalized clearance (Clp) and t1/2 estimates for DrotAA were calculated and compared between weight groups. RESULTS: Patient weight range was 59–227 kg. There were 32 patients ⩽135 kg and 20 patients >135 kg enrolled. Median Clp was 0.45 L/h/kg (interquartile range [IQR] 0.37–0.54) for patients ⩽135 kg and 0.42 L/h/kg (IQR 0.33–0.54) for patients >135 kg (p = 0.692). Median estimates of Css were 51.9 ng/mL (IQR 43.4–62.0) and 56.5 ng/mL (IQR 44.9–71.1; p = 0.570). In patients ⩽135 kg, DrotAA had a median t1/2 of 16.7 minutes (IQR 13.9–20.0) compared with 16.0 minutes (IQR 12.9–19.8) in patients >135 kg (p = 0.767), for a composite median t1/2 of 16.3 minutes (IQR 14.2–18.8). CONCLUSIONS: There is no statistically significant difference in Css concentrations or t1/2 of DrotAA between patients weighing ⩽135 kg and >135 kg. DrotAA should be dosed by actual body weight.

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