ABSTRACT
AIMS: Global guidelines recommend that all older patients with cancer receiving chemotherapy should undergo a geriatric assessment. However, utilisation of the geriatric assessment is often constrained by its time-intensive nature, which limits its adoption in settings with limited resources and high demand. There is a lack of evidence correlating the results of the geriatric assessment with survival from the Indian subcontinent. Therefore, the aims of the present study were to assess the impact of the geriatric assessment on survival in older Indian patients with cancer and to identify the factors associated with survival in these older patients. MATERIALS AND METHODS: This was an observational study, conducted in the geriatric oncology clinic of the Tata Memorial Hospital (Mumbai, India). Patients aged 60 years and older with cancer who underwent a geriatric assessment were enrolled. We assessed the non-oncological geriatric domains of function and falls, nutrition, comorbidities, cognition, psychology, social support and medications. Patients exhibiting impairment in two or more domains were classified as frail. RESULTS: Between June 2018 and January 2022, we enrolled 897 patients. The median age was 69 (interquartile range 65-73) years. The common malignancies were lung (40.5%), oesophagus (31.9%) and genitourinary (12.1%); 54.6% had metastatic disease. Based on the results of the geriatric assessment, 767 (85.4%) patients were frail. The estimated median overall survival in fit patients was 24.3 (95% confidence interval 18.2-not reached) months, compared with 11.2 (10.1-12.8) months in frail patients (hazard ratio 0.54; 95% confidence interval 0.41-0.72, P < 0.001). This difference in overall survival remained significant after adjusting for age, sex, primary tumour and metastatic status (hazard ratio 0.56; 95% confidence interval 0.41-0.74, P < 0.001). In the patients with a performance status of 0 or 1 (n = 454), 365 (80.4%) were frail; the median overall survival in the performance status 0-1 group was 33.0 months (95% confidence interval 24.31-not reached) in the fit group versus 14.4 months (95% confidence interval 12.25-18.73) in the frail patients (hazard ratio 0.50; 95% confidence interval 0.34-0.74, P = 0.001). In the multivariate analysis, the geriatric assessment domains that were predictive of survival were function (hazard ratio 0.68; 95% confidence interval 0.52-0.88; P = 0.003), nutrition (hazard ratio 0.64; 95% confidence interval 0.48-0.85, P = 0.002) and cognition (hazard ratio 0.67; 95% confidence interval 0.49-0.91, P = 0.011). DISCUSSION: The geriatric assessment is a powerful prognostic tool for survival among older Indian patients with cancer. The geriatric assessment is prognostic even in the cohort of patients thought to be the fittest, i.e. performance status 0 and 1. Our study re-emphasises the critical importance of the geriatric assessment in all older patients planned for cancer-directed therapy.
Subject(s)
Geriatric Assessment , Neoplasms , Aged , Humans , Middle Aged , Geriatric Assessment/methods , Neoplasms/drug therapy , Prognosis , Proportional Hazards Models , ComorbidityABSTRACT
This corrects the article DOI: 10.1038/bjc.2017.85.
ABSTRACT
BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive tumour originating in the thoracic mesothelium. Prognosis remains poor with 9- to 12-month median survival, and new targets for treatments are desperately needed. METHODS: Utilising an RNA interference (RNAi)-based screen of 40 genes overexpressed in tumours, including genes involved in the control of cell cycle, DNA replication and repair, we investigated potential therapeutic targets for MPM. Following in vitro characterisation of the effects of target silencing on MPM cells, candidates were assessed in tumour samples from 154 patients. RESULTS: Gene knockdown in MPM cell lines identified growth inhibition following knockdown of NDC80, CDK1 and PLK1. Target knockdown induced cell-cycle arrest and increased apoptosis. Using small-molecule inhibitors specific for these three proteins also led to growth inhibition of MPM cell lines, and Roscovitine (inhibitor of CDK1) sensitised cells to cisplatin. Protein expression was also measured in tumour samples, with markedly variable levels of CDK1 and PLK1 noted. PLK1 expression in over 10% of cells correlated significantly with a poor prognosis. CONCLUSION: These results suggest that RNAi-based screening has utility in identifying new targets for MPM, and that inhibition of NDC80, CDK1 and PLK1 may hold promise for treatment of this disease.
Subject(s)
CDC2 Protein Kinase/metabolism , Cell Cycle Proteins/metabolism , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Mesothelioma/drug therapy , Mesothelioma/metabolism , Nuclear Proteins/metabolism , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins/metabolism , RNA Interference , Apoptosis/drug effects , Apoptosis/genetics , Blood Proteins/genetics , CDC2 Protein Kinase/genetics , Cell Cycle/drug effects , Cell Cycle/genetics , Cell Cycle Checkpoints/drug effects , Cell Cycle Checkpoints/genetics , Cell Cycle Proteins/genetics , Cell Line, Tumor , Cisplatin/pharmacology , Cytoskeletal Proteins , DNA Repair/drug effects , DNA Repair/genetics , DNA Replication/drug effects , DNA Replication/genetics , Humans , Lung Neoplasms/genetics , Mesothelioma/genetics , Mesothelioma, Malignant , Molecular Targeted Therapy , Nuclear Proteins/genetics , Pleural Neoplasms/drug therapy , Pleural Neoplasms/genetics , Pleural Neoplasms/metabolism , Prognosis , Protein Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins/genetics , Purines/pharmacology , Retrospective Studies , Roscovitine , Polo-Like Kinase 1ABSTRACT
In the present investigation, pulsatile release beads were prepared by ionic gelation technique. Theophylline dual-cross-linked beads were prepared by dropping dispersed phase of theophylline, Delonix regia gum (DRG), and sodium alginate into the dispersion phase of different concentration of calcium chloride solution followed by aluminium chloride solution. The formulated beads were further coated by Eudragit L & S 100 in the ratio 1:2 w/w in order to achieve desired lag time. In vitro release study showed lag time of 57 h before release of theophylline from the formulated beads, which were found to be intact for 6 h. Thus, formulated dual cross-linked beads when administered at bed time may release theophylline when needed most for chronotherapeutics of early morning asthmatic attacks in chronic patients. In vivo radio imaging study carried out in New Zealand white strain rabbit confirms the findings of in vitro results.
Subject(s)
Asthma/drug therapy , Chronotherapy , Theophylline , Alginates/chemistry , Alginates/pharmacology , Animals , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Bronchodilator Agents/pharmacology , Chemistry, Pharmaceutical , Delayed-Action Preparations/pharmacology , Drug Carriers , Drug Delivery Systems , Drug Evaluation, Preclinical , Excipients , Fabaceae/chemistry , Glucuronic Acid/chemistry , Glucuronic Acid/pharmacology , Hexuronic Acids/chemistry , Hexuronic Acids/pharmacology , Humans , Mannose/chemistry , Mannose/pharmacokinetics , Microspheres , Polymethacrylic Acids/chemistry , Polymethacrylic Acids/pharmacology , Rabbits , Theophylline/pharmacologyABSTRACT
The eye presents unique opportunities and challenges when it comes to the delivery of pharmaceuticals. In the present study, ocular inserts of levofloxacin were prepared using chitosan and gelatin by solvent casting technique with an aim to improve therapeutic efficacy in the treatment of conjunctivitis. Prepared ocular inserts were then evaluated for film thickness, weight variation, content uniformity, percentage moisture loss and absorption. In vitro drug release studies were carried out using flow through apparatus that simulated the eye conditions. Optimized formulations were subjected to in vivo and stability studies to assess the effectiveness of the formulations. Finally in vitro in vivo correlation was established. Plasticizer like PEG was found to influence their effect on drug release. Prepared ocular inserts exhibited zero order kinetics which was confirmed by strong and positive correlation. The in vitro and in vivo drug release studies revealed that the formulations provide a best alternative to prolong the drug release at the end of 24 h and remained stable with intact at ambient conditions.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Chitosan , Conjunctiva , Drug Delivery Systems , Gelatin , Levofloxacin , Ofloxacin/administration & dosage , Animals , Anti-Bacterial Agents/pharmacokinetics , Conjunctivitis/drug therapy , Drug Compounding , Drug Design , Drug Stability , Humans , Male , Ofloxacin/pharmacokinetics , Plasticizers , Polyethylene Glycols , Polymers/chemistry , RabbitsABSTRACT
Anaesthesia was given from a Boyle's apparatus to 100 patients, using compressed air as the carrier gas.
