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The objective of the study was to develop a population pharmacokinetic model of pemetrexed and identify factors contributing to variability in exposure in Indian patients. Plasma samples were obtained from a cohort of 85 patients following 500 mg/m intravenous infusion and population pharmacokinetic analysis was performed using NONMEM (version 7.3.0). The stochastic approximation expectation maximization method was used to estimate parameters. The full covariate model approach was used by specifying clinically meaningful covariates a priori. Credible intervals obtained using Markov chain Monte Carlo Bayesian analysis were used to reduce the full covariate model by eliminating the covariates whose CI included the null. Model qualification was performed using visual predictive check and bootstrap. The final population parameter estimates and relative standard error for clearance (CL) was 3.3 L/h (10.8), central volume of distribution (V1) was 5.2 L (7.8), peripheral volume of distribution (V2) was 5.9 L (14.5) and intercompartmental clearance (Q) was 6.8 L/h (14.3). A large between-subject variability (50%-108% coefficient of variation) was observed in pharmacokinetic parameters. The percent coefficient of variation for the area under the plasma concentration-time curve from time zero to infinity was 72% and for maximum concentration was 68.25%. Diagnostic plots showed no major bias in the model. The final model included V1, V2, and Q scaled to body surface area raised to a fixed exponent of 1. Creatinine clearance and sex on clearance and albumin on V1 were statistically significant covariates based on Bayesian credible interval. However, traditional bootstrap resulted in a 95% confidence interval of the sex effect parameter including null. Given the size and nonsignificant sex effect in traditional bootstrap, it is considered clinically not significant.
This article was published in the following journal.
Name: Journal of clinical pharmacology
Chemotherapy is a mainstay treatment of metastatic non-small cell lung cancer. However, little is known about the comparative risk of hospitalization associated with commonly used chemotherapy regimen...
Recent Clinical trials of administration of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in combination with standard first-line chemotherapy have failed to improve survival...
First-line pemetrexed/carboplatin or cisplatin/bevacizumab compared with paclitaxel/carboplatin/bevacizumab in patients with advanced non-squamous non-small cell lung cancer with wild-type driver genes: A real-world study in China.
The study was conducted to compare the effectiveness and safety of pemetrexed/carboplatin or cisplatin/bevacizumab (PemPBev) and paclitaxel/carboplatin/bevacizumab (PacCBev) as first-line therapy for ...
A population-based study of outcomes in surgically resected T3N0 non-small cell lung cancer in the Netherlands, defined using TNM-7 and TNM-8; justification of changes and an argument to incorporate histology in the staging algorithm?
To study outcomes in patients surgically staged as pT3N0 non-small cell lung cancer (NSCLC) in a population registry, comparing TNM-7 and TNM-8 staging classifications.
Patients with N1 non-small cell lung cancer represent a heterogeneous population. The aim of this study is to determine the difference of survival rate between subtypes of N1 disease in surgically ...
The purposes of this study are to determine 1) the safety of pemetrexed and any side effects that might be associated with it 2) whether pemetrexed can help patients with small cell lung c...
This study is planned to answer questions about how the drug, matuzumab (EMD 72000), works and is part of an effort aimed to develop better treatment for advanced lung cancer by combining...
The purposes of this study are to determine: - the safety of pemetrexed and any side effects that might be associated with it - how much pemetrexed should be given to patients. ...
The purposes of this study are to determine: 1. The safety of Pemetrexed plus Gemcitabine and any side effects that might be associated with the combination of these two drugs. ...
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Malignant neoplasm arising from the epithelium of the BRONCHI. It represents a large group of epithelial lung malignancies which can be divided into two clinical groups: SMALL CELL LUNG CANCER and NON-SMALL-CELL LUNG CARCINOMA.
A form of highly malignant lung cancer that is composed of small ovoid cells (SMALL CELL CARCINOMA).
A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.
A basic helix-loop-helix leucine zipper (bHLHZ) transcription factor and proto-oncogene protein that functions in cell growth and proliferation. In mammals, it is highly expressed in the brain during embryogenesis and is essential for brain development; it is not expressed in adult tissues. Amplification or overexpression of N-Myc occurs in at least 20% of tumors and is associated with a poor prognosis in cases of NEUROBLASTOMA; ALVEOLAR RHABDOMYOSARCOMA; SMALL CELL LUNG CARCINOMA; and neuroendocrine prostate cancer.
A quinazoline derivative and ANTINEOPLASTIC AGENT that functions as a PROTEIN KINASE INHIBITOR for EGFR associated tyrosine kinase. It is used in the treatment of NON-SMALL CELL LUNG CANCER.
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Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells. In vertebrates, it is composed of blo...