Efficacy and Safety of Modified Pranlukast (Prakanon®) Compared with Pranlukast (Onon®): A Randomized, Open-Label, Crossover Study

Introduction: Pranlukast is a leukotriene receptor antagonist (LTRA) that is used as an additional controller of mild to moderate asthma. This study compared the efficacy and side effects of two bioequivalent preparations of pranlukast: original pranlukast (Onon®; Ono Pharmaceutical, Japan) and a modified formulation of pranlukast (Prakanon®; Yuhan Co, Korea) in patients with mild to moderate asthma. Methods: Of the 34 subjects screened, 30 patients who were using standard medication to control asthma and scored less than 20 points on the Asthma Control Test™ (ACT) were assigned randomly to one of the two groups in a prospective, open label, crossover study: group 1 received Prakanon® (150 mg/day) and group 2 received Onon® (450 mg/day) for 8 weeks each; after a 1-week rest period, the groups were switched to the alternative medication for further 8 weeks and monitored for 2 more weeks without study medication. Evaluation parameters included the ACT, quality of life questionnaire adult Korean asthmatics (QLQAKA), pulmonary function tests, peripheral blood tests, vital signs, and adverse events. Results: Thirty patients were enrolled and 21 completed the trial: 10 in group 1 and 11 in group 2. The baseline data of the two groups did not differ. No statistical significant differences were observed in efficacy and lung function at each time and in changes from baseline value between the two kinds of pranlukast. The final asthma control rate was 81% with Prakanon® and 76% with Onon®. There were no differences in vital signs and laboratory data at each time and in changes from baseline value between the two drugs. There were no differences in adverse events between the two drugs. The most common side effect was abdominal pain. Drug compliance was high, without differences between the two drugs. Conclusion: These findings suggest that Prakanon® which is an improved formulation of pranlukast at a lower dose than the original formulation, Onon®, has a similar efficacy and side effect profile in the control of persistent asthma.

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Physical Activity and Life Quality in Patients with Asthma and Osteoarthritis

10.53350/pjmhs211572343 ◽

2021 ◽

Vol 15 (7) ◽

pp. 2343-2347

Author(s):

YU. S. Ivanchuk ◽

L.V. Tribuntсeva ◽

A.V. Budnevsky ◽

N.I. Ostroushko ◽

YA. S. Shkatova ◽

...

Keyword(s):

Physical Activity ◽

Asthma Control ◽

Life Quality ◽

Sitting Time ◽

Control Group ◽

Moderate Activity ◽

Life Questionnaire ◽

Asthmatic Patients ◽

Group 2 ◽

Group 1

Background. Physical activity is associated with better asthma control and life quality in asthma. Osteoarthritis is one of the less studied comorbidities in asthmatic patients. Methods. The study included 38 patients diagnosed with asthma, 65 patients with asthma and osteoarthritis, and 40 volunteers who did not suffer from asthma and osteoarthritis. During the study, 3 groups were formed: Group 1 consisted of patients with asthma; Group 2 included patients with both asthma and osteoarthritis, Control group consisted of volunteers. Spirometry, Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Test (АСТ) were used in asthmatic patients. International Physical Activity Questionnaire (IPAQ) in its short from was filled by all the participants. Results. Both Group 1 and Group 2 did not engage in vigorous physical activity. Median of MET-min/week total (1825) was significantly less in Group 2 compared with Control and Group 1 (p=0.0000 and p=0.0169, respectively). MET-min/week total had positive correlations with ACT (r=0.50, p<0.05), AQLQ(S) total (r=0.58, p<0.05), AQLQ(S) activity domain (r=0.28, p<0.05), AQLQ(S) emotions domain (r=0.24, p<0.05), AQLQ (S) symptoms domain (r=0.34, p<0.05), FVC (r=0,28, p<0.05), FEV1 (r=0,37, p<0.05), Index Tiffno (r=0,18, p<0.05). Minutes/week sitting time had a negative correlation with ACT values (r=-0.33, p<0.05), AQLQ(S) total values (r=-0.39, p<0.05). Conclusion. Patients with asthma and osteoarthritis spend significantly less time on moderate activity, walking compared with asthmatics not suffering from osteoarthritis; they avoid vigorous activity. Higher physical activity is associated with better life quality, asthma control and lung function, thus paying attention to osteoarthritis in asthmatic patients is crucial. Key words: life quality, physical activity, asthma, osteoarthritis

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Life Quality and Cytokines Profile in Patients with Asthma and Osteoarthritis

International Journal of Biomedicine ◽

10.21103/article11(2)_oa2 ◽

2021 ◽

Vol 11 (2) ◽

pp. 137-140

Author(s):

Yuliya Ivanchuk ◽

Ludmila Tribuntceva ◽

Andrey Budnevsky ◽

Yanina Shkatova ◽

Evgeniy Ovsyannikov ◽

...

Keyword(s):

Quality Of Life ◽

Oxidative Damage ◽

Asthma Control ◽

Antioxidant Status ◽

Life Questionnaire ◽

Asthma Control Test ◽

Tnf Α ◽

Group 2 ◽

Group 1

The objective of this study was to evaluate levels of leptin, adiponectin, IL-4, IL-6, TNF-α, oxidative damage, and antioxidant status in patients with bronchial asthma (BA), compared to patients who suffer from both BA and osteoarthritis (OA), and analyze the quality of life in such patients. Methods and Results: The study included 103 patients (34 men and 69 women) diagnosed with moderate asthma aged from 30 to 70 years (mean age of 58.52±7.14 years). The levels of IL-4, IL-6, TNF-α, adiponectin, leptin, total antioxidant status (TAS), and total oxidative damage (TOD) were measured. Two questionnaires were used in this study: Asthma Quality of Life Questionnaire (AQLQ) and Asthma Control Test (АСТ). The levels of leptin, TNF-α, and Il-6 were significantly higher in Group 2 than in Group 1. On the contrary, the IL-4 level was higher in Group 1 than in Group 2. The TAS value was significantly higher in Group 1 than in Group 2 (P=0.0001). The TOD value was significantly higher in Group 2 than in Group 1 (P=0.0000). The domains of AQLQ(S) activity, symptoms, and emotions were decreased in patients of Group 2. The values of the ACT test were 18.0±2.61 points and 16.78±1.92 points in Group 1 and Group 2, respectively (P=0.0077). Conclusion: In patients with both asthma and osteoarthritis, levels of inflammatory cytokines, such as leptin, IL-6, and TNF-α, are significantly elevated as well as values of total oxidative status, which correlate with poorer asthma control and quality of life.

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Average bioequivalence of single 500 mg doses of two oral formulations of levofloxacin: a randomized, open-label, two-period crossover study in healthy adult Brazilian volunteers

Brazilian Journal of Pharmaceutical Sciences ◽

10.1590/s1984-82502015000100020 ◽

2015 ◽

Vol 51 (1) ◽

pp. 203-211 ◽

Cited By ~ 1

Author(s):

Eunice Kazue Kano ◽

Eunice Emiko Mori Koono ◽

Simone Grigoleto Schramm ◽

Cristina Helena dos Reis Serra ◽

Eduardo Abib Junior ◽

...

Keyword(s):

Adverse Events ◽

Crossover Study ◽

Vital Signs ◽

Spontaneous Report ◽

Hplc Method ◽

Regulatory Agencies ◽

Pharmacokinetic Parameters ◽

Open Label ◽

Average Bioequivalence ◽

Oral Formulations

Average bioequivalence of two 500 mg levofloxacin formulations available in Brazil, Tavanic(c) (Sanofi-Aventis Farmacêutica Ltda, Brazil, reference product) and Levaquin(c) (Janssen-Cilag Farmacêutica Ltda, Brazil, test product) was evaluated by means of a randomized, open-label, 2-way crossover study performed in 26 healthy Brazilian volunteers under fasting conditions. A single dose of 500 mg levofloxacin tablets was orally administered, and blood samples were collected over a period of 48 hours. Levofloxacin plasmatic concentrations were determined using a validated HPLC method. Pharmacokinetic parameters Cmax, Tmax, Kel, T1/2el, AUC0-t and AUC0-inf were calculated using noncompartmental analysis. Bioequivalence was determined by calculating 90% confidence intervals (90% CI) for the ratio of Cmax, AUC0-t and AUC0-inf values for test and reference products, using logarithmic transformed data. Tolerability was assessed by monitoring vital signs and laboratory analysis results, by subject interviews and by spontaneous report of adverse events. 90% CIs for Cmax, AUC0-t and AUC0-inf were 92.1% - 108.2%, 90.7% - 98.0%, and 94.8% - 100.0%, respectively. Observed adverse events were nausea and headache. It was concluded that Tavanic(c) and Levaquin(c) are bioequivalent, since 90% CIs are within the 80% - 125% interval proposed by regulatory agencies.

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The use of antiviral drug based on technologically processed antibodies to interferon-γ, CD4 receptor and histamine in the treatment of influenza in adults: results of a multicenter open-label randomized comparative trial with oseltamivir

Infekcionnye bolezni ◽

10.20953/1729-9225-2021-1-39-57 ◽

2021 ◽

Vol 19 (1) ◽

pp. 39-57

Author(s):

K.V. Zhdanov ◽

◽

R.F. Khamitov ◽

V.V. Rafalsky ◽

M.P. Mikhaylusova ◽

...

Keyword(s):

Immune Response ◽

B Cell ◽

Open Label ◽

Virus Elimination ◽

Antiviral Immune Response ◽

Cd4 Receptor ◽

Antiviral Efficacy ◽

Ifn Γ ◽

Group 2 ◽

Group 1

Objective. A multicenter open-label randomized controlled clinical trial was aimed to compare the efficacy of the study drug (SD) containing technologically processed affinity purified antibodies (high dilutions) to IFN-γ, CD4 receptor and histamine (Ergoferon) with oseltamivir, and evaluate the influence of SD on the antiviral immune response in adults with seasonal influenza. Patients and methods. 184 outpatients aged 18–70 with confirmed influenza of mild/moderate severity were included and randomized into 2 groups (in a 1:1 ratio). Patients received SD (Group 1, n = 92) or oseltamivir (Group 2, n = 92), according to the instructions for medical use for 5 days. As the primary endpoint, the percentage of patients with recovery/improvement was assessed (according to the data of the patient's diary on days 2–7 and according to the clinical examination on days 3 and 7). Additionally, the duration and severity of influenza symptoms, the percentage of patients with virus elimination (according to RT-PCR of nasopharyngeal samples), the percentage of patients with complications, the percentage of patients prescribed antipyretic drugs, the change in concentration of T cell (IL-2, IL-18, IFN-γ) and B cell antigen-specific (IL-4, IL-16) immune response regulators in serum, the leukocyte phenotypes on days 1, 3 and 7 were evaluated. Statistical analysis was performed using a “Non-Inferiority” design (or no less efficiency/safety). Intention-to-Treat (ITT) analysis data are presented. Results. According to patients’ self-assessment, 53.3% of patients in Group 1 recovered/improved on the 6th day in the morning and 65.2% – in the evening (vs. 53.3% and 57.6% in Group 2, respectively). There were 73.9% recovered/ improved patients on the 7th day in the morning (vs. 67.4% in Group 2). A generalized analysis showed that the treatment results in both groups were comparable (p < 0.0001). According to objective medical examination, 79.3% of patients in the SD group and 74.0% of patients in the Оseltamivir group recovered/improved on the 7th day (p < 0.0001). The antiviral efficacy of SD was not inferior to oseltamivir, which was confirmed by comparable periods of virus elimination, duration and severity of fever and other influenza symptoms. A moderate activating effect of SD on the immune system was evaluated. A significant, compared to oseltamivir, increase in the concentration of IL-2 and IL-4 on the 3rd day of treatment (p = 0.03 and p = 0.04 vs. the oseltamivir group), and IFN-γ on the 3rd and the 7th days (p = 0.012 and p < 0.0001, respectively, vs. the oseltamivir group). No stimulating effect of SD on the growth and differentiation of immune cells was found. Conclusion. SD is effective and safe in the treatment of patients with influenza. The therapeutic and antiviral efficacy of SD is comparable to that of oseltamivir. The antiviral activity of SD affects the interferon system and the concentration of the cytokines IL-2 and IL-4, regulators of the T and B cell immune response. At the same time, there is no significant stimulation of interferon production with further development of hyporeactivity. Key words: influenza, oseltamivir, therapy, cytokines, Еrgoferon

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The Threshold of Admission Glycemia as a Predictor of Adverse Events in Diabetic and Non-Diabetic Patients with Acute Coronary Syndrome

Clinical medicine Cardiology ◽

10.4137/cmc.s2289 ◽

2009 ◽

Vol 3 ◽

pp. CMC.S2289 ◽

Cited By ~ 3

Author(s):

Taysir S. Garadah ◽

Salah Kassab ◽

Qasim M. Al-Shboul ◽

Abdulhai Alawadi

Keyword(s):

Acute Coronary Syndrome ◽

Adverse Events ◽

Diabetic Patients ◽

Stress Hyperglycemia ◽

Coronary Syndrome ◽

History Of ◽

Group 3 ◽

Group 2 ◽

High Level ◽

Group 1

Recent studies indicated a high prevalence of hyperglycemia in non-diabetic patients presenting with acute coronary syndrome (ACS). However, the threshold of admission glucose (AG) as a predictor of adverse events in ACS is unclear. Objective The aim of this study was to assess the threshold of admission glucose (AG) as a predictor of adverse events including Major Acute Cardiac Events (MACE) and mortality, during the first week of admitting patients presenting with ACS. Material and Methods The data of 551 patients with ACS were extracted and evaluated. Patients were stratified according to their blood glucose on admission into three groups: group 1: <7 mmol/L (n = 200, 36.3%) and group 2: >7 mmol/L and <15 mmol/L (n = 178, 32.3%) and group 3: ≥15 mmol/L (n = 173, 31.4%). Stress hyperglycemia was arbitrarily defined as AG levels > 7 mmol/L (group 2 and 3). Patients with ACS were sub-divided into two groups: patients with unstable angina (UA, n = 285) and those with ST segment elevation myocardial Infarction (STEMI, n = 266) and data were analyzed separately using multiple regression analysis. Results The mean age of patients was 59.7 ± 14.8 years and 63% were males. The overall mortality in the population was 8.5% (5.4% in STEMI and 3.1% in UA) patients. In STEMI patients, the odds ratio of stress hyperglycemia as predictor of mortality in group 3 compared with group 1 was 3.3 (CI 0.99-10.98, P < 0.05), while in group 2 compared with group 1 was 2.4 (CI: 0.75-8.07, P = 0.065) after adjustment for age and sex. Similarly, in UA patients, the odds ratio of stress hyperglycemia in group 3 compared with group 1 was 2.7 (CI 0.37-18.98, P < 0.05), while in group 2 compared with group 1 was 2.4 (CI: 0.4-15.2, P = 0.344) after adjustment for age and sex. The incidence of more than 2 MACE in both STEMI and UA patients was higher in group 3 compared with the other two groups. Regression analysis showed that history of DM, high level of LDL cholesterol, high level of HbA1c, and anterior infarction were significant predictors of adverse events while other risk factors such as BMI, history of hypertension and smoking were of no significance. Conclusion This study indicates that the stress hyperglycemia on admission is a powerful predictor of increased major adverse events and hospital mortality in patients with acute coronary syndrome.

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Pharmacokinetics and safety of XAV-19, a swine glyco-humanized polyclonal anti-SARS-CoV-2 antibody, for COVID-19-related moderate pneumonia: a randomized, double-blind, placebo-controlled, phase IIa study

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01237-21 ◽

2021 ◽

Author(s):

Benjamin Gaborit ◽

Eric Dailly ◽

Bernard Vanhove ◽

Régis Josien ◽

Karine Lacombe ◽

...

Keyword(s):

Adverse Events ◽

High Serum ◽

Serum Concentrations ◽

Serious Adverse Events ◽

Double Blind ◽

Good Tolerability ◽

Group 3 ◽

Group 2 ◽

Group 1

Objective: We assessed the pharmacokinetics and safety of XAV-19, a swine glyco-humanized polyclonal antibody against SARS-CoV-2, in COVID-19-related moderate pneumonia. To evaluate the optimal dose and safety of XAV-19 during this first administration to patients with COVID-19-related moderate pneumonia. Methods : In this phase 2a trial, adults with COVID-19-related moderate pneumonia of ≤10 days duration were randomized to infusion of XAV-19 0.5mg/kg at day 1 and day 5 (group 1), 2mg/kg at day 1 and day 5 (group 2), 2mg/kg at day 1 (group 3) or placebo. Results : Eighteen patients (n=7 for group 1, n=1 for group 2, n=5 for group 3, and n=5 for placebo) were enrolled. Baseline characteristics were similar across groups, XAV-19 serum concentrations (μg/mL, median, range) at C max and at day 8 were 9.1 (5.2-18.1) and 6.4 (2.8-11.9), 71.5 and 47.2, and 50.4 (29.1-55.0) and 20.3 (12.0-22.7) for groups 1, 2 and 3, respectively (p=0.012). Terminal half-life (median, range) was estimated at 11.4 (5.5-13.9) days for 2 mg/kg of XAV-19 at day 1. Serum XAV-19 concentrations were above the target concentration of 10 μg/mL (tow fold the in vitro 100% inhibitory concentration [IC 100 ]) from the end of perfusion to more than 8 days for XAV-19 2 mg/kg at day 1. No hypersensitivity or infusion-related reactions were reported during treatment, there was no discontinuation for adverse events and no serious adverse events related to study drug. Conclusions : Single intravenous dose of 2mg/kg of XAV-19 demonstrated high serum concentrations, predictive of potent durable neutralizing activity with good tolerability. Trial registration: ClinicalTrials.gov Identifier: NCT04453384

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Does Teleradiology Improve Inter-hospital Management of Head-Injury?

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100021867 ◽

1997 ◽

Vol 24 (3) ◽

pp. 235-239 ◽

Cited By ~ 31

Keyword(s):

Head Injury ◽

Adverse Events ◽

Hospital Management ◽

District General Hospital ◽

Therapeutic Interventions ◽

Head Injured ◽

Hospital Transfer ◽

Group 2 ◽

Injured Patients ◽

Group 1

ABSTRACT:Objective:In many countries, neurosurgical care is concentrated in regional centres, which often necessitates the inter-hospital transfer of patients with head injury for optimal treatment. The aim of this study was to evaluate the role of teleradiology in the management of head-injured patients when referred from a district general hospital to a tertiary neurosurgical centre.Methods:Prospective data were collected over a fifteen month period from March '95 to May '96. Head-injured patients referred without the facility of teleradiology (Group 1), were compared to similar patients referred with teleradiologie images (Group 2), with particular regard to therapeutic intervention before transfer and adverse events during transfer.Results:There were 28 patients in Group 1 and 35 in Group 2, of which 31 were transferred. Both groups were comparable with respect to age, admission Glasgow Coma Scale score, and intracranial pathology. For patients transferred with teleradiology consultation (Group 2), therapeutic interventions were more (32.1% vs. 10.7%, p = 0.06), adverse events during transfer were significantly lower (6.4% vs. 32.1%, p = 0.01), and transfer time was reduced (72 vs. 80 minutes, p = 0.38). Four patients in Group 2 were treated by a mobile neurosurgical team at the referring hospital because of rapid clinical deterioration.Conclusion:Our findings indicate that teleradiology has an important role in improving inter-hospital management of head-injured patients.

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Abstract 16929: Are Patients Implanted with a Ventricular Assist Device as Destination Therapy Created Equal? Analysis of Outcomes by Implant Indications

Circulation ◽

10.1161/circ.130.suppl_2.16929 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Simon Maltais ◽

Mary E Davis ◽

Nicholas A Haglund ◽

John A Schirger ◽

Keith Aaronson ◽

...

Keyword(s):

Adverse Events ◽

Ventricular Assist Device ◽

Left Ventricular ◽

Advanced Age ◽

Destination Therapy ◽

Gi Bleeding ◽

Assist Device ◽

Ventricular Assist ◽

Group 2 ◽

Group 1

Introduction: A growing number of patients are implanted with a continuous-flow left ventricular assist device (CF-LVAD) for destination therapy (DT). Hypothesis: We sought to determine if indication for DT was associated with adverse events and survival. Methods: Between May 2004 and May 2014, 211 patients (age 66 (19-82), 89% male) underwent implantation of a HeartMate II CF-LVAD. The cohort was stratified according to primary listed indication for DT at time of implant: Group 1=advanced age (n=124, 59%); Group 2=high BMI (n=33, 16%), and Group 3=end-organ comorbidities (n=54, 25%). DT patients who later became BTT were eliminated for homogeneity. Results: Follow-up was available in all patients for a total of 376 patient-years of support (median 1.4 years). Preoperative characteristics (creatinine 1.5, INTERMACS 3, IABP 49%) were comparable between groups (all p>0.05). Overall 1, 3 and 5-year survival was 81%, 58%, and 41%, respectively. Kaplan-Meier analysis revealed comparable survival between groups stratified by DT indications (Figure, p=0.07). While gastrointestinal (GI) bleeding was more frequent in patients implanted for advanced age DT indications (p=0.01, group 1 vs group 2 and 3), the incidence of adverse events (pump thrombus/exchange, stroke) was comparable between groups. After adjusting for covariates (creatinine, hemoglobin, prior sternotomy and diabetes), Cox regression analysis demonstrated only preoperative renal dysfunction (HR 1.86 CI 1.28, 2.69; p=0.001) and lower Hemoglobin (HR 0.82 CI 0.71, 0.95; p=0.008) were associated with late mortality after implantation. Conclusions: Advanced age remains the most frequent contemporary indication for DT in patients undergoing CF-LVAD implantation. Indication for DT implantation does not influence long-term survival. Elderly patients may be at greater risk of GI bleeding events. These results continue to favor a uniform selection process across the spectrum of DT indications.

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Treatment of Optic Canal Decompression Combined with Umbilical Cord Mesenchymal Stem (Stromal) Cells for Indirect Traumatic Optic Neuropathy: A Phase 1 Clinical Trial

Ophthalmic Research ◽

10.1159/000512469 ◽

2020 ◽

Vol 64 (3) ◽

pp. 398-404

Author(s):

Jia Li ◽

Xu Bai ◽

Xiaoyue Guan ◽

Hongfeng Yuan ◽

Xiang Xu

Keyword(s):

Visual Acuity ◽

Adverse Events ◽

Phase 1 ◽

Optic Canal ◽

Traumatic Optic Neuropathy ◽

Corrected Visual Acuity ◽

Group 2 ◽

Best Corrected Visual Acuity ◽

Group 1

Purpose: This study was aimed to investigate the safety and feasibility of umbilical cord-derived mesenchymal stem cell (MSC) transplantation in patients with traumatic optic neuropathy (TON). Methods: This is a single-center, prospective, open-labeled phase 1 study that enrolled 20 patients with TON. Patients consecutively underwent either optic canal decompression combined with MSC local implantation treatment (group 1) or only optic canal decompression (group 2). Patients were evaluated on the first day, seventh day, first month, third month, and sixth month postoperatively. Adverse events, such as fever, urticarial lesions, nasal infection, and death, were recorded at each visit. The primary outcome was changes in best-corrected visual acuity. The secondary outcomes were changes in color vision, relative afferent pupillary defect, and flash visual evoked potential. Results: All 20 patients completed the 6-month follow-up. None of them had any systemic or ocular complications. The change in best-corrected visual acuity at follow-up was not significantly different between group 1 and group 2 (p > 0.05); however, group 1 showed better visual outcome than group 2. Both groups showed significant improvements in vision compared with the baseline (p < 0.05); however, there were no statistically significant differences between the groups (p > 0.05). In addition, no adverse events related to local transplantation were observed in the patients. Conclusions: A single, local MSC transplantation in the optic nerve is safe for patients with TON.

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E7389, a novel anti-tubulin, in patients with refractory breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.653 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 653-653 ◽

Cited By ~ 5

Author(s):

J. BlumL. Forero ◽

M. K. Heiskala ◽

N. Meneses ◽

K. Chandrawansa ◽

F. Fang ◽

...

Keyword(s):

Breast Cancer ◽

Performance Status ◽

Safety Data ◽

Synthetic Analog ◽

Open Label ◽

Ecog Performance Status ◽

Group 2 ◽

Grade 3 ◽

Cycle Group ◽

Group 1

653 Background: E7389 is a synthetic analog of halichondrin B, with a broad anti- proliferative activity against tumor cells. Methods: E7389 was evaluated in an open-label, single-arm Phase II trial as monotherapy for patients with refractory breast cancer (≥2 prior chemotherapy regimens, which must have included an anthracycline and a taxane). E7389 was administered as an IV bolus of 1.4 mg/m2 on Days 1, 8, and 15 of a 28-day cycle (group 1), or on Days 1 and 8 of a 21-day cycle (group 2). The primary efficacy endpoint was ORR. Results: As of 9 December 2005, 88 patients had received treatment, 68 in group 1 and 20 in group 2. Median age was 55 yrs (range 36–84) and ECOG performance status 0–1. Sixty-six percent of the tumors were ductal carcinomas, 6% lobular, and 27% were unclassified. Sixty percent of the tumors were ER+, 47% PR+, and 17% Her2/neu 3+. The patients had received at least two previous regimens, with a median number of 5 (range 2–14). Forty-eight percent of the patients had also used hormonal therapy. Forty-nine patients in group 1 and 12 patients in group 2 had completed their 2nd cycle of treatment, and twenty-one in group1 and 1 in group 2 their 4th cycle. Safety: The major toxicity related to study drug was neutropenia. Among 73 patients with preliminary safety data available, two patients had Grade 3 febrile neutropenia, and 31 had Grade 3 or 4 neutropenia or leukopenia. The other Grade 3 toxicities encountered in more than two patients were dehydration (4 patients) and dyspnea (4 patients). Grade 3 peripheral neuropathy was reported in 2 patients. Efficacy: At the end of cycle four there were 10 (15.2%) confirmed partial responses (PRs) out of 66 evaluable patients in group 1, and 1 confirmed PR (5.6%) out of 18 evaluable patients in group 2. The median duration of confirmed responses was 113 days. Conclusions: Based on the safety and efficacy in this refractory breast cancer population, E7389 appears to be a therapy worthy of continued investigation in patients with heavily pretreated breast cancer. In order to comply with the current demand for individualized cancer care, bio-markers which would predict the sensitivity to E7389 are being searched in the tumor samples of the patients in the current and forthcoming studies. [Table: see text]

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