10 research outputs found
Pranlukast: A review of its use in the management of asthma
Pranlukast (Onon\uae, Azlaire\uae), is an orally administered, selective, competitive antagonist of the cysteinyl leukotrienes (LT) C4, LTD4 and LTE4. It is indicated for the prophylactic treatment of chronic bronchial asthma in paediatric and adult patients. The efficacy of pranlukast 225mg twice daily in adults with mild to moderate asthma was demonstrated in double-blind, placebo- or azelastine-controlled studies of 4 or 8 weeks' duration. The drug at this dosage was superior to both comparators in improving mean attack scores and morning and/or evening peak expiratory flow rates, and decreasing the use of rescue bronchodilators (p < 0.05). In limited clinical studies, pranlukast 225mg twice daily appeared to be as effective as montelukast 10mg once daily and zafirlukast 40mg twice daily in adults with mild to moderate asthma. Tachyphylaxis was absent when the drug was administered for up to 4 years. In patients requiring high-dose inhaled corticosteroid therapy, pranlukast 225mg twice daily plus a halved dosage of inhaled corticosteroid was as effective as the original dosage of inhaled corticosteroid. Pranlukast was also effective in patients with mild to severe asthma in a clinical practice setting. In a double-blind trial, greater improvements in most outcome measures were observed with pranlukast than with oxatomide in children and adolescents with asthma. In clinical trials, pranlukast was well tolerated in adult and paediatric patients with asthma, with an adverse event profile similar to that of placebo. Gastrointestinal events and hepatic function abnormalities were the most commonly reported adverse events. No clinically significant differences in adverse event profiles between pranlukast, zafirlukast or montelukast were shown in limited comparisons. Although Churg-Strauss syndrome has been noted in pranlukast recipients, a direct causal relationship is unlikely. Conclusions: Pranlukast is a well tolerated and effective preventative treatment in adult and paediatric patients with persistent asthma of all severities. In some patients, pranlukast may be beneficial when added to low-dose inhaled corticosteroids; it may also be a viable alternative to increasing inhaled corticosteroid dosages. The efficacy of pranlukast relative to placebo has been confirmed; its efficacy relative to other therapy awaits further investigation. Nonetheless, pranlukast is a useful therapeutic option (with as-required short-acting \u3b22-agonists), either as preventative monotherapy for the treatment of mild persistent asthma or in conjunction with inhaled corticosteroids in the management of moderate or severe persistent asthma
The role of Lyn kinase in the development of imatinib resistance in chronic myelogenous leukemia
Pan-Asian adaptation of the EHNS-ESMO-ESTRO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with squamous cell carcinoma of the head and neck.
The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of squamous cell carcinoma (SCC) of the oral cavity, larynx, oropharynx and hypopharynx was published in 2020. It was therefore decided by both the ESMO and the Korean Society of Medical Oncology (KSMO) to convene a special, virtual guidelines meeting in July 2021 to adapt the ESMO 2020 guidelines to consider the potential ethnic differences associated with the treatment of SCCs of the head and neck (SCCHN) in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with SCCHN (excluding nasopharyngeal carcinomas) representing the oncological societies of Korea (KSMO), China (CSCO), India (ISMPO), Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter was discussed when appropriate. This manuscript provides a series of expert recommendations (Clinical Practice Guidelines) which can be used to provide guidance to health care providers and clinicians for the optimisation of the diagnosis, treatment and management of patients with SCC of the oral cavity, larynx, oropharynx and hypopharynx across Asia
Limited impact of palliative chemotherapy on survival in advanced solid tumours in patients with poor performance status
Pharmacotherapy of Complicated Urinary Tract and Intra-abdominal Infections with Doripenem
Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE): a randomised, open-label, multicentre, phase 3 trial
Background: Survival outcomes are poor for patients with metastatic urothelial carcinoma who receive standard, first-line, platinum-based chemotherapy. We assessed the overall survival of patients who received durvalumab (a PD-L1 inhibitor), with or without tremelimumab (a CTLA-4 inhibitor), as a first-line treatment for metastatic urothelial carcinoma. Methods: DANUBE is an open-label, randomised, controlled, phase 3 trial in patients with untreated, unresectable, locally advanced or metastatic urothelial carcinoma, conducted at 224 academic research centres, hospitals, and oncology clinics in 23 countries. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1. We randomly assigned patients (1:1:1) to receive durvalumab monotherapy (1500 mg) administered intravenously every 4 weeks; durvalumab (1500 mg) plus tremelimumab (75 mg) administered intravenously every 4 weeks for up to four doses, followed by durvalumab maintenance (1500 mg) every 4 weeks; or standard-of-care chemotherapy (gemcitabine plus cisplatin or gemcitabine plus carboplatin, depending on cisplatin eligibility) administered intravenously for up to six cycles. Randomisation was done through an interactive voice–web response system, with stratification by cisplatin eligibility, PD-L1 status, and presence or absence of liver metastases, lung metastases, or both. The coprimary endpoints were overall survival compared between the durvalumab monotherapy versus chemotherapy groups in the population of patients with high PD-L1 expression (the high PD-L1 population) and between the durvalumab plus tremelimumab versus chemotherapy groups in the intention-to-treat population (all randomly assigned patients). The study has completed enrolment and the final analysis of overall survival is reported. The trial is registered with ClinicalTrials.gov, NCT02516241, and the EU Clinical Trials Register, EudraCT number 2015-001633-24. Findings: Between Nov 24, 2015, and March 21, 2017, we randomly assigned 1032 patients to receive durvalumab (n=346), durvalumab plus tremelimumab (n=342), or chemotherapy (n=344). At data cutoff (Jan 27, 2020), median follow-up for survival was 41·2 months (IQR 37·9–43·2) for all patients. In the high PD-L1 population, median overall survival was 14·4 months (95% CI 10·4–17·3) in the durvalumab monotherapy group (n=209) versus 12·1 months (10·4–15·0) in the chemotherapy group (n=207; hazard ratio 0·89, 95% CI 0·71–1·11; p=0·30). In the intention-to-treat population, median overall survival was 15·1 months (13·1–18·0) in the durvalumab plus tremelimumab group versus 12·1 months (10·9–14·0) in the chemotherapy group (0·85, 95% CI 0·72–1·02; p=0·075). In the safety population, grade 3 or 4 treatment-related adverse events occurred in 47 (14%) of 345 patients in the durvalumab group, 93 (27%) of 340 patients in the durvalumab plus tremelimumab group, and in 188 (60%) of 313 patients in the chemotherapy group. The most common grade 3 or 4 treatment-related adverse event was increased lipase in the durvalumab group (seven [2%] of 345 patients) and in the durvalumab plus tremelimumab group (16 [5%] of 340 patients), and neutropenia in the chemotherapy group (66 [21%] of 313 patients). Serious treatment-related adverse events occurred in 30 (9%) of 345 patients in the durvalumab group, 78 (23%) of 340 patients in the durvalumab plus tremelimumab group, and 50 (16%) of 313 patients in the chemotherapy group. Deaths due to study drug toxicity were reported in two (1%) patients in the durvalumab group (acute hepatic failure and hepatitis), two (1%) patients in the durvalumab plus tremelimumab group (septic shock and pneumonitis), and one (<1%) patient in the chemotherapy group (acute kidney injury). Interpretation: This study did not meet either of its coprimary endpoints. Further research to identify the patients with previously untreated metastatic urothelial carcinoma who benefit from treatment with immune checkpoint inhibitors, either alone or in combination regimens, is warranted. Funding: AstraZeneca. © 2020 Elsevier Lt