Adverse Effects of Immune Checkpoint Therapy in Cancer Patients Visiting the Emergency Department of a Comprehensive Cancer Center.

Ann Emerg Med. 2019 01;73(1):79-87

Authors: El Majzoub I, Qdaisat A, Thein KZ, Win MA, Han MM, Jacobson K, Chaftari PS, Prejean M, Reyes-Gibby C, Yeung SJ

Abstract
STUDY OBJECTIVE: Cancer immunotherapy is evolving rapidly and is transforming cancer care. During the last decade, immune checkpoint therapies have been developed to enhance the immune response; however, specific adverse effects related to autoimmunity are increasingly apparent. This study aims to fill the knowledge gap related to the spectrum of immune-related adverse effects among cancer patients visiting emergency departments (EDs).
METHODS: We performed a retrospective review of patients treated with immune checkpoint therapy who visited the ED of a comprehensive cancer center between March 1, 2011, and February 29, 2016. Immune-related adverse effects from the ED visits were identified and profiled. We analyzed the association of each immune-related adverse effect with overall survival from the ED visit to death.
RESULTS: We identified 1,026 visits for 628 unique patients; of these, 257 visits (25.0%) were related to one or more immune-related adverse effects. Diarrhea was the most common one leading to an ED visit. The proportions of ED visits associated with diarrhea, hypophysitis, thyroiditis, pancreatitis, or hepatitis varied significantly by immune checkpoint therapy agent. Colitis was significantly associated with better prognosis, whereas pneumonitis was significantly associated with worse survival.
CONCLUSION: Cancer patients treated with ipilimumab, nivolumab, or pembrolizumab may have a spectrum of immune-related adverse effects that require emergency care. Future studies will need to update this profile as further novel immunotherapeutic agents are added.

PMID: 29880440 [PubMed - indexed for MEDLINE]

A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients.

AIDS. 2018 07 17;32(11):1431-1442

Authors: Eron JJ, Orkin C, Gallant J, Molina JM, Negredo E, Antinori A, Mills A, Reynes J, Van Landuyt E, Lathouwers E, Hufkens V, Jezorwski J, Vanveggel S, Opsomer M, AMBER study group

Abstract
OBJECTIVES: To investigate efficacy and safety of a single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg vs. darunavir/cobicistat plus emtricitabine/tenofovir disoproxyl fumarate (TDF) (control) in antiretroviral-treatment-naive, HIV-1-infected adults.
DESIGN: Phase-3, randomized, active-controlled, double-blind, international, multicenter, noninferiority study (NCT02431247).
METHODS: Seven hundred and twenty-five participants were randomized (1 : 1) to D/C/F/TAF (362) or control (363). The primary objective was to demonstrate noninferiority of D/C/F/TAF vs. control for percentage viral load less than 50 copies/ml (FDA-snapshot analysis) at 48 weeks (10% margin).
RESULTS: At week 48, D/C/F/TAF was noninferior to control (91.4 vs. 88.4% achieved viral load <50 copies/ml, respectively; difference 2.7%; 95% CI -1.6 to 7.1; P < 0.0001), with 4.4 vs. 3.3% of patients, respectively, having viral load greater or equal to 50 copies/ml. No treatment-emergent mutations associated with darunavir or TAF/TDF resistance were observed in either group. One patient (D/C/F/TAF) was identified with M184I/V conferring resistance to emtricitabine. Incidences of grades 3 and 4 adverse events (5 vs. 6%), serious adverse events (5 vs. 6%) and adverse event-related discontinuations (2 vs. 4%) were low and similar between groups. Mean decrease in urine protein/creatinine ratio was greater with D/C/F/TAF than control (-22.42 vs. -10.34 mg/g, P = 0.033). Mean percentage change in bone mineral density with D/C/F/TAF vs. control was 0.21 vs. -2.73%, P < 0.0001 (hip), -0.68 vs. -2.38%, P = 0.004 (lumbar spine), and -0.26 vs. -2.97%, P < 0.0001 (femoral neck). Median change from baseline in total cholesterol/HDL-cholesterol ratio was 0.20 vs. 0.08, P = 0.036.
CONCLUSION: D/C/F/TAF achieved a high virologic suppression rate (91.4%) and was noninferior to darunavir/cobicistat with F/TDF. D/C/F/TAF also demonstrated the bone and renal safety advantages of TAF in combination with darunavir/cobicistat.

PMID: 29683855 [PubMed - indexed for MEDLINE]

Multiple drug intolerance syndrome and multiple drug allergy syndrome: Epidemiology and associations with anxiety and depression.

Allergy. 2018 10;73(10):2012-2023

Authors: Blumenthal KG, Li Y, Acker WW, Chang Y, Banerji A, Ghaznavi S, Camargo CA, Zhou L

Abstract
BACKGROUND: The epidemiology of multiple drug intolerance syndrome (MDIS) and multiple drug allergy syndrome (MDAS) is poorly characterized. We used electronic health record (EHR) data to describe prevalences of MDIS and MDAS and to examine associations with anxiety and depression.
METHODS: Patients with ≥3 outpatient encounters at Partners HealthCare System from 2008 to 2015 were included. Patients with MDIS had intolerances to ≥3 drug classes, and patients with MDAS had hypersensitivities to ≥2 drug classes. Psychiatric conditions and comorbidities were defined from the EHR and used in multivariable logistic regression models to assess the relation between anxiety/depression and MDIS/MDAS.
RESULTS: Of 746 888 patients, 47 634 (6.4%) had MDIS and 8615 (1.2%) had MDAS; 3171 (0.4%) had both. Anxiety (adjusted odds ratio [aOR] 1.72 [1.65, 1.80]), depression (aOR 1.46 [1.41, 1.52]), and both anxiety and depression (aOR 1.97 [1.86, 2.08]) were associated with increased odds of MDIS. Depression was associated with increased odds of MDAS (aOR 1.41 [1.28, 1.56]), but there were no clear associations with anxiety (aOR 1.13 [0.99, 1.30]) nor both depression and anxiety (aOR 1.13 [0.92, 1.38]).
CONCLUSION: While 6% of patients had MDIS, only 1% had MDAS. MDIS was associated with both anxiety and depression; patients with both anxiety and depression had an almost twofold increased odds of MDIS. MDAS was associated with a 40% increased odds of depression, but there was no significant association with anxiety. Psychological assessments may be useful in the evaluation and treatment of patients with MDIS and MDAS; physiologic causes for MDAS warrant further investigation.

PMID: 29574787 [PubMed - indexed for MEDLINE]

22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2019/10/23

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2019/10/23

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Simulating the effect of sodium channel blockage on cardiac electromechanics.

Proc Inst Mech Eng H. 2019 Oct 18;:954411919882514

Authors: Shalaby N, Zemzemi N, Elkhodary K

Abstract
There is growing interest to better understand drug-induced cardiovascular complications and to predict undesirable side effects at as early a stage in the drug development process as possible. The purpose of this paper is to investigate computationally the influence of sodium ion channel blockage on cardiac electromechanics. To do so, we implement a myofiber orientation dependent passive stress model (Holzapfel-Ogden) in the multiphysics solver Chaste to simulate an imaged physiological model of the human ventricles. A dosage of a sodium channel blocker was then applied and its inhibitory effects on the electrical propagation across ventricles were modeled. We employ the Kerckhoffs active stress model to generate electrically excited contractile behavior of myofibers. Our predictions indicate that a delay in the electrical activation of ventricular tissue caused by the sodium channel blockage translates to a delay in the mechanical biomarkers that were investigated. Moreover, sodium channel blockage was found to increase left ventricular twist. A multiphysics computational framework from the cell level to the organ level was thus used to predict the effect of sodium channel blocking drugs on cardiac electromechanics.

PMID: 31625448 [PubMed - as supplied by publisher]

Assessment of effectiveness and safety of biosimilar infliximab (CT-P13) in a real-life setting for treatment of patients with active rheumatoid arthritis or ankylosing spondylitis.

Curr Med Res Opin. 2018 10;34(10):1763-1769

Authors: Codreanu C, Šírová K, Jarošová K, Batalov A

Abstract
OBJECTIVE: To assess the effectiveness and safety of infliximab biosimilar, CT-P13, administered in a real-life setting to adult patients with active rheumatoid arthritis (RA) or ankylosing spondylitis (AS).
METHODS: This multi-center, non-interventional, observational study was conducted in Bulgaria, the Czech Republic, and Romania. A total of 151 patients with severe active RA (n = 81) or AS (n = 70) were enrolled and treated with CT-P13 for 24 weeks, according to current medical recommendations. Effectiveness was assessed using the 4-item Disease Activity Score 28 with C-reactive protein (DAS28-CRP) for RA patients, and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for AS patients. Safety was assessed by withdrawals and adverse events (AEs).
RESULTS: A total of 129 patients (RA: 67; AS: 62) were included in the effectiveness analysis. CT-P13 treatment significantly improved DAS28-CRP scores at 12 and 24 weeks (p = .0001 vs baseline for both timepoints) in patients with RA and BASDAI scores at 12 and 24 weeks (p = .0001 vs baseline for both timepoints) in patients with AS. CRP levels were significantly reduced at 12 and 24 weeks (p = .0001 vs baseline for both timepoints). Among 713 infusions, 34 AEs were reported (4.8% of infusions), of which 11 were considered related to CT-P13 treatment. Two of seven serious AEs were considered possibly (hepatocellular injury) or definitely (dyspnoea due to allergic infusion reaction) treatment-related. Eight patients discontinued CT-P13 due to AEs and four patients were withdrawn due to therapeutic failure.
CONCLUSIONS: CT-P13 was effective and safe in a real-life setting in patients with active RA or AS.

PMID: 29439591 [PubMed - indexed for MEDLINE]

[Description of contributing factors in adverse events related to patient safety and their preventability].

Aten Primaria. 2018 10;50(8):486-492

Authors: Guerra-García MM, Campos-Rivas B, Sanmarful-Schwarz A, Vírseda-Sacristán A, Dorrego-López MA, Charle-Crespo Á

Abstract
OBJECTIVE: To assess the extent of healthcare related adverse events (AEs), their effect on patients, and their seriousness. To analyse the factors leading to the development of AEs, their relationship with the damage caused, and their degree of preventability.
DESIGN: Retrospective descriptive study.
LOCATION: Porriño, Pontevedra, Spain, Primary Care Service, from January-2014 to April-2016.
PARTICIPANTS AND/OR CONTEXT: Reported AEs were entered into the Patient Safety Reporting and Learning System (SiNASP).
METHOD: The variables measured were: Near Incident (NI) an occurrence with no effect or harm on the patient; Adverse Event (AE) an occurrence that affects or harms a patient. The level of harm is classified as minimal, minor, moderate, critical, and catastrophic. Preventability was classified as little evidence of being preventable, 50% preventable, and sound evidence of being preventable.
DATA ANALYSIS: percentages and Chi-squared test for qualitative variables; P<.05 with SPSS.15.
DATA SOURCE: SiNASP. Ethical considerations: approved by the Research Ethics Committee (2016/344).
RESULTS: There were 166 recorded AEs (50.6% in males, and 46.4% in women. The mean age was 60.80years). Almost two-thirds 62.7% of AEs affected the patient, with 45.8% causing minimal damage, while 2.4% caused critical damages. Healthcare professionals were a contributing factor in 71.7% of the AEs, with the trend showing that poor communication and lack of protocols were related to the damage caused. Degree of preventability: 96.4%.
CONCLUSIONS: Most AEs affected the patient, and were related to medication, diagnostic tests, and laboratory errors. The level of harm was related to communication problems, lack of, or deficient, protocols and a poor safety culture.

PMID: 29183678 [PubMed - indexed for MEDLINE]

[Impact of medium-term outcomes of inappropriate prescribing in older patients discharged from a short stay unit].

Aten Primaria. 2018 10;50(8):467-476

Authors: Rodríguez Del Río E, Perdigones J, Fuentes Ferrer M, González Del Castillo J, González Armengol J, Borrego Hernando MI, Arias Fernández ML, Martín-Sánchez FJ

Abstract
OBJECTIVE: To study the association between the potential inappropriate prescriptions (PIP) and the 30 and 180-day adverse event rate after discharge from a Short Stay Unit (SSU).
METHODOLOGY: A retrospective cohort observational study was conducted on patients aged ≥75years discharged from an SSU from February to April, 2014. STOPP-START criteria version2 was used. The main outcome was 30 and 180-day adverse event rate after being discharged.
RESULTS: A total of 179 patients, with a mean age of 84 (SD5) years were included. The presence of ≥1PIP after being discharged was not associated with a 30 and 180-day composite adverse event. Patients with ≥1PIP related to a cerebro-cardiovascular process were at higher risk of an adverse event at 30 days after discharge (adjusted OR, 2.1; 95%CI: 1.0-3.2; P=.045), those with ≥1PIP related to neuropsychiatric process and risk of fall were at higher risk of increased 30-day functional impairment (adjusted OR, 6.3; 95%CI: 1.7-22.5; P=.005), and those with ≥1PIP related to omission of cardiovascular system were at higher risk of 180-day hospital readmission (adjusted OR, 3.6; 95%CI: 1.5-8.3; P=.003).
CONCLUSIONS: The presence of adverse events in older patients discharged from SSU may be associated with PIP, identified by STOPP-START criteria, and more specifically with drugs related to cardiovascular, neuropsychiatric disorders, and falls.

PMID: 29079010 [PubMed - indexed for MEDLINE]

15 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2019/10/18

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

15 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2019/10/18

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Safinamide in Clinical Practice: A Spanish Multicenter Cohort Study.

Brain Sci. 2019 Oct 11;9(10):

Authors: Martí-Andrés G, Jiménez-Bolaños R, Arbelo-González JM, Pagonabarraga J, Duran-Herrera C, Valenti-Azcarate R, Luquin MR

Abstract
Background: Safinamide is an approved drug for the treatment of motor fluctuations of Parkinson's Disease (PD) patients with a potential benefit on non-motor symptoms (NMS). Methods: A retrospective multicenter cohort study was conducted, in which the clinical effect of safinamide on both motor and NMS was assessed by the Clinical Global Impression of Change scale. Furthermore, we assessed the appearance of adverse events (AEs) and its effect on dyskinesia, that were also recorded in non-fluctuating PD patients and in those previously treated with rasagiline. Results: We included 213 PD patients who received safinamide in addition to their regular levodopa therapy. Thirty-five withdrew prematurely from safinamide, mainly because of AEs. Out of 178, clinical improvement on motor and NMS was found in 76.4% and 26.2%, respectively. A total of 44 reported AEs of mild intensity. We did not find a difference concerning the clinical benefit or AEs when comparing either patients who had or had not been taking Monoamine Oxidase B Inhibitor (MAOB-I) previously or between patients with and without motor complications. Conclusions: Safinamide is an effective and safe add-on to levodopa drug for PD patients. Moreover, safinamide could elicit an additional clinical improvement in PD patients previously treated with other MAOB-I and in non- fluctuating patients with suboptimal motor control.

PMID: 31614574 [PubMed]

Meropenem-Vaborbactam in the Treatment of Acute Bacterial Infections.

J Clin Med. 2019 Oct 11;8(10):

Authors: Lai CC, Chen CC, Tang HJ

Abstract
This study reports the integrated analysis of two phase III studies of meropenem-vaborbactam in the treatment of acute bacterial infections. Targeting Antibiotic Non-Susceptible Gram-Negative Organisms (TANGO) I compared the clinical efficacy and tolerability of meropenem-vaborbactam and piperacillin-tazobactam in the treatment of complicated urinary tract infection (cUTI)/acute pyelonephritis (APN). TANGO II compared the effect and safety of meropenem-vaborbactam and best-available therapy in the treatment confirmed/suspect carbapenem-resistant Enterobacteriaceae infections. The clinical cure rates at end of treatment (EOT) and test of cure (TOC) among the meropenem-vaborbactam group were non-inferior to those of the control group (at EOT, 92.5% versus 89.3%, risk ratio (RR) 1.27, 95% CI 0.64-2.50; at TOC, 86.2% versus 81.7%, RR 1.37, 95% CI 0.62-3.01). Meropenem-vaborbactam was non-inferior to comparators for microbiological eradication at EOT and TOC (at EOT, 93.3% versus 88.3%, RR 1.21, 95% CI 0.74-1.97; at TOC, 66.5% versus 59.9%, RR 1.12, 95% CI 0.97-1.30). In the subgroup of patients with cUTI/APN, meropenem-vaborbactam had similar overall success rate to the control group at EOT (RR 1.05, 95% CI 1.01-1.09) and at TOC (RR 1.05, 95% CI 0.93-1.19). Meropenem-vaborbactam had a similar risk of treatment-emergent adverse events, events leading to discontinuation of the study drug, any serious adverse events, life-threatening adverse events, drug-related adverse events, and risk of death to comparators. In conclusion, meropenem-vaborbactam was noninferior to comparators for clinical cure and microbiological eradication in the treatment of acute bacterial infection, particularly cUTI/APN, and meropenem-vaborbactam was as tolerable as comparators.

PMID: 31614430 [PubMed]

Frequency of low-grade adverse events and quality of life during chemotherapy determine patients' judgement about treatment in advanced-stage thoracic cancer.

Support Care Cancer. 2019 Sep;27(9):3563-3572

Authors: de Mol M, Visser S, den Oudsten BL, Lodder P, van Walree N, Belderbos H, Aerts JG

Abstract
PURPOSE: In lung cancer, the preservation of well-being is warranted given the limited prognosis. Chemotherapy may negatively influence health-related quality of life (HRQoL) due to adverse events. However, patients' judgement about this negative impact is not well understood. We examined the relationship between expectations, feelings about side effects, and satisfaction with therapy and (HR)QoL in advanced-stage thoracic cancer and investigated which of these factors has the highest impact on (HR)QoL.
METHODS: Sixty-nine patients completed the Cancer Therapy Satisfaction Questionnaire (CTSQ), the World Health Organization Quality of Life-BREF (WHOQOL-BREF), and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Multiple regression analyses were performed to investigate the relation of the CTSQ domains (i.e., expectations of therapy, feelings about side effects, satisfaction with therapy) with (HR)QoL and simple regression analyses to identify the factors of the CTSQ domain that was most often associated with (HR)QoL.
RESULTS: Feelings about side effects were associated with the (HR)QoL domain/scale scores (i.e., WHOQOL-BREF domains: β = 0.36 to 0.58; EORTC QLQ-C30 scales: β = 0.33 to 0.61) except social relationships of the WHOQOL-BREF. Low-grade adverse events were related to feelings about side effects (β = - 0.326; P = 0.007).
CONCLUSIONS: Patients experiencing negative feelings about side effects have worse (HR)QoL. Additional care should be provided to prevent low-grade adverse events.

PMID: 30690684 [PubMed - indexed for MEDLINE]

Prevalence of oral side effects of chemotherapy and its relationship with periodontal risk: a cross sectional study.

Support Care Cancer. 2019 Sep;27(9):3479-3490

Authors: García-Chías B, Figuero E, Castelo-Fernández B, Cebrián-Carretero JL, Cerero-Lapiedra R

Abstract
PURPOSE: To determine the prevalence of professionally reported oral side effects of chemotherapy and the self-reported oral side effects and whether both prevalences could be related to the periodontal risk of the patients.
METHODS: A cross-sectional study with patients undergoing chemotherapy treatment was carried out. Demographic, oral hygiene habits, and cancer-related data were collected while the patient was receiving the chemotherapy infusion. Patient's oral status, measured according to the oral-assessment guide for patients in hospital environments, patient-related outcomes (PROMs), measured by a visual analogue scale, and patient's periodontal risk were analyzed using validated questionnaires. Data was reported in means and standard deviations (SD) in quantitative variables and in counts, prevalence, and 95% confidence intervals (CI) in qualitative variables. ANOVA test and chi-squared tests were used to compare oral side effects among different periodontal risk groups.
RESULTS: Three hundred sixty-nine patients were included in the study. The prevalence of professionally reported oral side effects was 86.99% (95% confidence interval CI 83.54%; 90.44%). The prevalence of self-reported oral side effects was 89.70% (95% CI 86.59; 92.82). The most common oral side effects were xerostomia (73.4%), dysgeusia (61.8%), and dry lips (54.2%). More oral alterations were found in patients with worse periodontal risk (p < 0.001).
CONCLUSIONS: The prevalence of oral side effects (professional or self-reported) is higher than 85% in patients undergoing chemotherapy. This prevalence increases as the risk of developing periodontal disease does.

PMID: 30675665 [PubMed - indexed for MEDLINE]

Bulgarian Experience with Adverse Drug Reaction Reports from Patients and Consumers - Retrospective Data-base Study.

Folia Med (Plovdiv). 2018 Sep 01;60(3):447-453

Authors: Getova VI, Georgiev SR, Stoimenova AH, Petkova-Georgieva ES

Abstract
BACKGROUND: Since 2012, in compliance with the changes in the European legislation, the Bulgarian Drug Agency (BDA) has been receiving adverse drug reaction (ADR) reports directly from patients as well as from healthcare professionals and marketing authorization holders (MAH). Adverse reaction reports from patients and consumers have different characteristics from those sent by healthcare professionals. Moreover, they may require specific algorithm and assessment methods in order to be informative and beneficial to the pharmacovigilance system.
AIM: The study aims to analyze the data-base of consumer reports in Bulgaria in order to distinguish and classify the main characteristics of the ADR reports from non-healthcare professionals.
MATERIALS AND METHODS: In-depth analysis of the Bulgarian data-base of consumer ADR reports for 2012-2016 was conducted. The criteria include patient demographic characteristics, preferred method of reporting, seriousness and expectedness criteria and most frequently reported pharmacological groups.
RESULTS: The data showed the current trends in patient reporting in the country. It also marked new courses for development of the spontaneous reporting system and collection of safety data. The analysis of the data-base showed a rather stable level of patient reporting with a tendency for constant growth every year. Bulgaria follows the world tendencies for high number of reports for insufficiently studied ADRs which meet the seriousness criteria. The review of the most frequently reported ATC codes could lead to the conclusion that the current pharmacovigi-lance methods are not sensitive enough for specific groups of medicines.
CONCLUSIONS: The results from the conducted study confirm the importance of patient reporting as a valuable source of information on adverse drug reactions. Moreover, it draws the attention to the lack of more sensitive methods for evaluation of drug safety in specific pharmacological groups. Maintenance of consumer-friendly ADR reporting system and innovative assessment algorithms should be the future directions for development in post-marketing surveillance.

PMID: 30355838 [PubMed - indexed for MEDLINE]

Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A Comparative Study From Sudan.

J Glob Oncol. 2018 09;4:1-9

Authors: Osman AAM, Elhassan MMA, AbdElrahim BHA, Ahmed FHA, Yousif JBH, Ahmed MAM, Abdelhafeez RHA, Ahmed UMY

Abstract
PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) is a distressing adverse effect. Neurokinin-1 receptor antagonist (NK1RA)-containing regimens are the standard regimens for CINV prophylaxis in patients with cancer receiving highly or moderately emetogenic chemotherapy (HEC or MEC). NK1RA agents are expensive and were not registered in Sudan. Recently, regimens containing olanzapine, the available and affordable medication in Sudan, were introduced as another option. This study aimed to compare the efficacy of an olanzapine-containing regimen with the antiemetic regimen that was currently used in our institute for CINV prophylaxis in HEC/MEC settings.
PATIENTS AND METHODS: The study prospectively compared an olanzapine-containing regimen (acute phase: olanzapine, ondansetron, dexamethasone; delayed phase: olanzapine, ondansetron) with an ondansetron/dexamethasone regimen (acute phase: ondansetron, dexamethasone; delayed phase: ondansetron) in adult patients with cancer receiving HEC or MEC. The study outcomes were complete response (CR; no emesis and no rescue medications) and nausea control (no nausea), which were assessed in the acute (0 to 24 hours), delayed (24 to 120 hours), and overall (0 to 120 hours) phases.
RESULTS: The study included 131 patients (olanzapine-containing: 50 patients; ondansetron/dexamethasone: 81 patients). CR and nausea control were higher in the olanzapine-containing than in the ondansetron/dexamethasone regimen (CR: acute phase, 86% v 71.6%; P = .086; delayed phase, 72% v 30.9%; P < .001; overall phase, 66% v 25.9%; P < .001; nausea control: acute phase, 86% v 74.1%; P = .127; delayed phase, 76% v 34.6%; P < .001; overall phase, 72% v 29.6%; P < .001). The major toxicity of olanzapine was grade 1 and 2 sedation or drowsiness (25 patients).
CONCLUSION: An olanzapine-containing regimen has better efficacy for prevention of CINV in the HEC/MEC setting. Oncologists working in a limited-resource setting should be familiar with olanzapine-containing regimens, because NK1RA agents are not affordable and not easily available.

PMID: 30241275 [PubMed - indexed for MEDLINE]

Efficacy/toxicity dose-finding using hierarchical modeling for multiple populations.

Contemp Clin Trials. 2018 08;71:162-172

Authors: Cunanan KM, Koopmeiners JS

Abstract
Traditionally, Phase I oncology trials evaluate the safety profile of a novel agent and identify a maximum tolerable dose based on toxicity alone. With the development of biologically targeted agents, investigators believe the efficacy of a novel agent may plateau or diminish before reaching the maximum tolerable dose while toxicity continues to increase. This motivates dose-finding based on the simultaneous evaluation of toxicity and efficacy. Previously, we investigated hierarchical modeling in the context of Phase I dose-escalation studies for multiple populations and found borrowing strength across populations improved operating characteristics. In this article, we discuss three hierarchical extensions to commonly used probability models for efficacy and toxicity in Phase I-II trials and adapt our previously proposed dose-finding algorithm for multiple populations to this setting. First, we consider both parametric and non-parametric bivariate models for binary outcomes and, in addition, we consider an under-parameterized model that combines toxicity and efficacy into a single trinary outcome. Our simulation results indicate hierarchical modeling increases the probability of correctly identifying the optimal dose and increases the average number of patients treated at the optimal dose, with the under-parameterized hierarchical model displaying desirable and robust operating characteristics.

PMID: 29936124 [PubMed - indexed for MEDLINE]

11 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2019/10/16

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

11 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2019/10/16

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.