Search

Aim: To understand US physicians' frontline (1L) treatment preferences/decision-making for stage III/IV classic Hodgkin lymphoma (cHL). Materials & methods: Medical oncologists and/or hematologists (≥2 years' practice experience) who treat adults with stage III/IV cHL were surveyed online (October–November 2020). Results: Participants (n = 301) most commonly considered trial efficacy/safety data and national guidelines when selecting 1L cHL treatments. Most physicians (91%) rated overall survival (OS) as the most essential attribute when selecting 1L treatment. Variability was seen among regimen selection for hypothetical newly diagnosed patients, with OS cited as the most common reason for regimen selection. Conclusion: While treatment selection varied based on patient characteristics, US physicians consistently cited OS as the top factor considered when selecting a 1L treatment for cHL. Classic Hodgkin lymphoma (cHL) is a type of cancer that grows in lymph nodes. The researchers created a survey to assess how doctors in the USA choose medicine to treat patients who are newly diagnosed with an advanced stage of cHL (stage 3 or 4 out of 4 stages). We surveyed 301 doctors who treat patients with cHL. When choosing a medicine to treat cHL, most doctors said they consider results from research studies, how well the medicine works, information on the medicine's safety and recommendations in official guidelines. Most doctors said that overall survival (how long the patient survives after being diagnosed with cHL) is the most important outcome they consider when choosing a medicine to treat cHL. During the survey, doctors saw four unique patient profiles. These profiles differed in age, disease stage (how far along the cHL is) and other illnesses the patient has. While medicine choice was different across profiles, overall survival was still the reason for choosing each individual patient's medicine. These survey results show that doctors in the USA highly consider overall survival when choosing medicine for patients newly diagnosed with an advanced stage of cHL. Survey of US physicians who treat patients with #cHL shows that while frontline treatment selection varies based on individual characteristics of those with stage III/IV cHL, the regimen's reported overall survival is the top consideration. [ABSTRACT FROM AUTHOR]

Background: Cancer patients with bone metastasis or multiple myeloma (MM) are at increased risk for painful and irreversible bone complications known as skeletal-related events (SREs), which include bone fractures, spinal cord compression, and radiation or surgery to the bone.1,2 Bone-targeting agents (BTAs) such as zoledronic acid and denosumab reduce the risk and delay time to SREs. However, despite the significant morbidity and poor prognosis associated with SREs, only 50% to 70% of eligible patients receive BTAs as protective therapy.3,4 Objectives: To better understand patient awareness about cancer bone health and SRE treatment options, we conducted a patient-centric survey designed to identify (1) the source, type, and extent of bone health education received as part of supportive care, and (2) potential opportunities for improvement of cancer bone health education to enhance appropriate BTA use. Methods: The BonE HeAlth EduCatiOn Needs Assessment (BEACON) study was an online survey conducted by GRYT Health, Inc. through unique direct-to-patient outreach enrolling consenting US adult cancer patients with self-reported bone metastasis from breast cancer (BrC), prostate cancer (PrC), or lung cancer (LC), or with MM. Survey categories included demographics, primary cancer diagnosis and treatments, extent and overall satisfaction with bone health education received (amount, source, mode, and timing relative to diagnosis), and use of a BTA. Patients received a $50 gift card for participation. Results: The 125 patients who participated in this study had the following types of cancer: 74 (59%) BrC, 8 (6%) PrC, 7 (6%) LC, and 36 (29%) MM. Patients ranged in age from 26 to 79 years (mean of 48 years); 99 (79%) were female. Seventy-one (57%) had experienced at least 1 SRE (fracture: 32%; spinal cord compression: 22%; radiation to the bone: 38%; surgery to the bone: 19%); 92 (74%) were currently receiving a BTA. Awareness of cancer bone health and protection was low to moderate; on average, patients reported knowledge of 50% of educational messages related to bone health included in the survey and 54% of messages related to bone health protection. Sources of information most commonly reported were oncologists (n = 118, 94%), followed by nurse practitioners (n = 66, 53%) and registered nurses (n = 65, 52%). The same number of patients reported that they received information through a discussion with a healthcare provider (HCP) (n = 110, 88%) and would like to receive information from an HCP (n = 110, 88%), but discrepancies were seen in other modes of information sharing. For example, 49% of patients reported wanting printed information (handout, pamphlet), but only 18% reported having received printed materials. Overall, patient-reported satisfaction with bone health education indicated an unmet need, with 39 (31%) patients responding "not satisfied" or "slightly satisfied." Dissatisfaction was higher for patients not currently treated with a BTA (39% [13/33] not/slightly satisfied) than for treated patients (28% [26/92] not/slightly satisfied). Conclusions: In this study largely comprised of BrC and MM patients, notable gaps in cancer patient awareness about the risk of SRE and BTA treatment options suggest there is an important need for improved communication and education strategies on this topic. [ABSTRACT FROM AUTHOR]

Warfarin, a commonly prescribed oral anticoagulant medication, is highly effective in treating deep vein thrombosis and pulmonary embolism. However, the clinical dosing of warfarin is complicated by high interindividual variability in drug exposure and response and its narrow therapeutic index. CYP2C9 genetic polymorphism and drug-drug interactions (DDIs) are substantial contributors to this high variability of warfarin pharmacokinetics (PK), among numerous factors. Building a physiology-based pharmacokinetic (PBPK) model for warfarin is not only critical for a mechanistic characterization of warfarin PK but also useful for investigating the complicated dose-exposure relationship of warfarin. Thus, the objective of this study was to develop a PBPK model for warfarin that integrates information regarding CYP2C9 genetic polymorphisms and their impact on DDIs. Generic PBPK models for both S- and R-warfarin, the two enantiomers of warfarin, were constructed in R with the mrgsolve package. As expected, a generic PBPK model structure did not adequately characterize the warfarin PK profile collected up to 15 days following the administration of a single oral dose of warfarin, especially for S-warfarin. However, following the integration of an empirical target-mediated drug disposition (TMDD) component, the PBPK-TMDD model well characterized the PK profiles collected for both S- and R-warfarin in subjects with different CYP2C9 genotypes. Following the integration of enzyme inhibition and induction effects, the PBPK-TMDD model also characterized the PK profiles of both S- and R-warfarin in various DDI settings. The developed mathematic framework may be useful in building algorithms to better inform the clinical dosing of warfarin. SIGNIFICANCE STATEMENT: The present study found that a traditional physiology-based pharmacokinetic (PBPK) model cannot sufficiently characterize the pharmacokinetic profiles of warfarin enantiomers when warfarin is administered as a single dose, but a PBPK model with a target-mediated drug disposition mechanism can. After incorporating CYP2C9 genotypes and drug-drug interaction information, the developed model is anticipated to facilitate the understanding of warfarin disposition in subjects with different CYP2C9 genotypes in the absence and presence of both cytochrome P450 inhibitors and cytochrome P450 inducers., (Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics.)

The objective of this study is to conduct a population pharmacokinetic (PK) model-based analysis on 10 warfarin metabolites (4'-, 6-, 7-, 8- and 10-hydroxylated (OH)-S- and R- warfarin), when warfarin is administered alone or together with either fluconazole or rifampin. One or two compartment PK models expanded from target mediated drug disposition (TMDD) models developed previously for warfarin enantiomers were able to sufficiently characterize the PK profiles of 10 warfarin metabolites in plasma and urine under different conditions. Model-based analysis shows CYP2C9 mediated metabolic elimination pathways are more inhibitable by fluconazole (% formation CL (CL f ) of 6- and 7-OH-S-warfarin decrease: 73.2% and 74.8%) but less inducible by rifampin (% CL f of 6- and 7-OH-S-warfarin increase: 85% and 75%), compared with non-CYP2C9 mediated elimination pathways (% CL f of 10-OH-S-warfarin and CL R of S-warfarin decrease in the presence of fluconazole: 65.0% and 15.3%; % CL f of 4'- 8- and 10-OH-S-warfarin increase in the presence of rifampin: 260%, 127% and 355%), which potentially explains the CYP2C9 genotype-dependent DDIs exhibited by S-warfarin, when warfarin is administrated together with fluconazole or rifampin. Additionally, for subjects with CYP2C9 *2 and *3 variants, a model-based analysis of warfarin metabolite profiles in subjects with various CYP2C9 genotypes demonstrates CYP2C9 mediated elimination is less important and non-CYP2C9 mediated elimination is more important, compared with subjects without these variants. To our knowledge, this is so far one of the most comprehensive population-based PK analyses of warfarin metabolites in subjects with various CYP2C9 genotypes under different co-medications. Significance Statement The studies we wish to publish are potentially impactful. The need for a TMDD pharmacokinetic model and the demonstration of genotyped-dependent drug interactions may explain the extensive variability in dose-response relationships that are seen in the clinical dose adjustments of warfarin., (Copyright © 2020 American Society for Pharmacology and Experimental Therapeutics.)

At some point, anyone with knowledge of drug metabolism and enzyme kinetics started out knowing little about these topics. This chapter was specifically written with the novice in mind. Regardless of the enzyme one is working with or the goal of the experiment itself, there are fundamental components and concepts of every experiment using drug metabolism enzymes. The following case studies provide practical tips, techniques, and answers to questions that may arise in the course of conducting such experiments. Issues ranging from assay design and development to data interpretation are addressed. The goal of this section is to act as a starting point to provide the reader with key questions and guidance while attempting his/her own work.