Mapping PRO-CTCAE responses to clinician-graded adverse events, dose reductions, interruptions, and discontinuations in phase I cancer trials.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2014-2014
Author(s):  
Geoffrey Alan Watson ◽  
Zachary William Neil Veitch ◽  
Daniel Shepshelovich ◽  
Zhihui (Amy) Liu ◽  
Anna Spreafico ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Medical Records ◽  
Phase 1 ◽  
Patient Report Outcome ◽  
Disease Characteristics ◽  
Life Scale ◽  
First Time ◽  
The Relationship ◽  
Dose Reductions

2014 Background: Typically symptomatic adverse events (sy-AEs) on clinical trials are reported by clinicians using the CTCAE. To complement clinician collected sy-AEs and understand tolerability better, the patient report outcome version of the CTCAE (PRO-CTCAE) has been developed to provide the patient (pt) perspective on severity of AEs (graded scale 0-4) and their interference in daily life (scale 0-4). The aim of this study was to correlate PRO responses with the grade (G) of AEs, dose interruptions/reductions and dose limiting toxicities (DLTs). Methods: Pts enrolled on phase 1 clinical trials at Princess Margaret were surveyed electronically on tablet using the full library of items for PRO-CTCAE. The PRO-CTCAE was administered at baseline (prior to therapy), mid-cycle 1, and mid-cycle 2. AEs on study were recorded by physicians using the CTCAE. The electronic medical records were analyzed for an association between reported sy-AEs and PRO score. Summary statistics were used to describe patient and disease characteristics, as well as the outcomes. Spearman’s method was used to correlate PRO severity and interference responses. Logistic regression was used to assess which factors were associated with CTCAE G 3-4 vs G 2 AEs. Results: We analyzed 158 pts: median age 60yrs, 77 (49%) were male; all were ECOG ≤1 and 22, 55 and 81 pts completed 1, 2 and 3 surveys, respectively. Clinician reported G2, 3 and 4 sy-AEs occurred in 81, 47 and 3 pts, respectively and all of these were related to a PRO item except 5% (4/81), 9% (4/47) and 33% (1/3), respectively because either the AE occurred after 3rd time point or patient not able to complete the PRO (encephalitis). Sy-AEs causing dose interruptions, reductions, DLTs and discontinuations occurred in 45 (28%), 12 (7.5%), 5 (3%) and 12 (7.5%) pts, respectively; with a corresponding PRO item in 40 (89%), 12 (100%), 4 (80%) and 11(92%) pts, respectively. For patients who had CTCAE G2, G3/4 AEs, interruptions and discontinuations, their severity and inference levels were positively correlated (coefficient 0.49, p < 0.001; 0.45, p < 0.001 0.59, p < 0.001, 0.86, p < 0.001). Dose interruptions (p = 0.0027) and reductions (p = 0.0061) were significantly associated with G3-4 compared to G2 AEs. Conclusions: This is the first time an association between PRO-CTCAE severity and interference; and CTCAE G2, 3, 4 AEs, dose interruptions and discontinuations has been demonstrated. Additional modelling and more patient data are being analyzed to explore the relationship.

scholarly journals Adverse events of special interest in clinical trials of rheumatoid arthritis, psoriatic arthritis, ulcerative colitis and psoriasis with 37 066 patient-years of tofacitinib exposure

RMD Open ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. e001595
Author(s):  
Gerd R Burmester ◽  
Peter Nash ◽  
Bruce E Sands ◽  
Kim Papp ◽  
Lori Stockert ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ulcerative Colitis ◽  
Clinical Trials ◽  
Psoriatic Arthritis ◽  
Adverse Events ◽  
Special Interest ◽  
Phase 1 ◽  
Incidence Rates ◽  
Study Data ◽  
System Organ Class

ObjectivesTo analyse adverse events (AEs) of special interest across tofacitinib clinical programmes in rheumatoid arthritis (RA), psoriatic arthritis (PsA), ulcerative colitis (UC) and psoriasis (PsO), and to determine whether the incidence rates (IRs; unique patients with events per 100 patient-years) of these events are consistent across diseases.MethodsThe analysis included data from patients exposed to ≥1 dose of tofacitinib in phase 1, 2, 3 or 3b/4 clinical trials and long-term extension (LTE) studies (38 trials) in RA (23 trials), PsA (3 trials), UC (5 trials) and PsO (7 trials). All studies were completed by or before July 2019, except for one ongoing UC LTE study (data cut-off May 2019). IRs were obtained for AEs of special interest.Results13 567 patients were included in the analysis (RA: n=7964; PsA: n=783; UC: n=1157; PsO: n=3663), representing 37 066 patient-years of exposure. Maximum duration of exposure was 10.5 years (RA). AEs within the ‘infections and infestations’ System Organ Class were the most common in all diseases. Among AEs of special interest, IRs were highest for herpes zoster (non-serious and serious; 3.6, 1.8, 3.5 and 2.4 for RA, PsA, UC and PsO, respectively) and serious infections (2.5, 1.2, 1.7 and 1.3 for RA, PsA, UC and PsO, respectively). Age-adjusted and sex-adjusted mortality ratios (weighted for country) were ≤0.2 across cohorts.ConclusionsThe tofacitinib safety profile in this analysis was generally consistent across diseases and with longer term follow-up compared with previous analyses.

scholarly journals Nervous and Muscular Adverse Events after COVID-19 Vaccination: A Systematic Review and Meta-Analysis of Clinical Trials

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 939
Author(s):  
Jiaxin Chen ◽  
Yuangui Cai ◽  
Yicong Chen ◽  
Anthony P. Williams ◽  
Yifang Gao ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Events ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Phase 1 ◽  
Cochrane Library ◽  
Categorical Variables ◽  
Control Group ◽  
Open Label

Background: Nervous and muscular adverse events (NMAEs) have garnered considerable attention after the vaccination against coronavirus disease (COVID-19). However, the incidences of NMAEs remain unclear. We aimed to calculate the pooled event rate of NMAEs after COVID-19 vaccination. Methods: A systematic review and meta-analysis of clinical trials on the incidences of NMAEs after COVID-19 vaccination was conducted. The PubMed, Medline, Embase, Cochrane Library, and Chinese National Knowledge Infrastructure databases were searched from inception to 2 June 2021. Two independent reviewers selected the study and extracted the data. Categorical variables were analyzed using Pearson’s chi-square test. The pooled odds ratio (OR) with the corresponding 95% confidence intervals (CIs) were estimated and generated with random or fixed effects models. The protocol of the present study was registered on PROSPERO (CRD42021240450). Results: In 15 phase 1/2 trials, NMAEs occurred in 29.2% vs. 21.6% (p < 0.001) vaccinated participants and controls. Headache and myalgia accounted for 98.2% and 97.7%, and their incidences were 16.4% vs. 13.9% (OR = 1.97, 95% CI = 1.28–3.06, p = 0.002) and 16.0% vs. 7.9% (OR = 3.31, 95% CI = 2.05–5.35, p < 0.001) in the vaccine and control groups, respectively. Headache and myalgia were more frequent in the newly licensed vaccines (OR = 1.97, 95% CI = 1.28–3.06, p = 0.02 and OR = 3.31, 95% CI = 2.05–5.35, p < 0.001) and younger adults (OR = 1.40, 95% CI = 1.12–1.75, p = 0.003 and OR = 1.54, 95% CI = 1.20–1.96, p < 0.001). In four open-label trials, the incidences of headache, myalgia, and unsolicited NMAEs were 38.7%, 27.4%, and 1.5%. Following vaccination in phase 3 trials, headache and myalgia were still common with a rate of 29.5% and 19.2%, although the unsolicited NMAEs with incidence rates of ≤ 0.7% were not different from the control group in each study. Conclusions: Following the vaccination, NMAEs are common of which headache and myalgia comprised a considerable measure, although life-threatening unsolicited events are rare. NMAEs should be continuously monitored during the ongoing global COVID-19 vaccination program.

scholarly journals RELATIONSHIP BETWEEN ADVERSE EVENTS PREVALENCE, PATIENT SAFETY CULTURE AND PATIENT SAFETY PERCEPTION IN A SINGLE SAMPLE OF PATIENTS: A CROSS-SECTIONAL STUDY

2021 ◽  
Author(s):  
Monica Susana Chirinos ◽  
Carola Orrego ◽  
Cesar Montoya ◽  
Rosa Sunol
Keyword(s):  
Patient Safety ◽  
Adverse Events ◽  
Safety Culture ◽  
Medical Records ◽  
Patient Safety Culture ◽  
Single Sample ◽  
Inverse Association ◽  
Cross Sectional ◽  
Safety Perception ◽  
The Relationship

Background: Fostering the understanding of the relationship between the prevalence of adverse events (AEP), the patient safety culture of healthcare professionals (PSC) and patient safety perception (PSP) could be an important step to operationalizing patient safety through an integration of different perspectives. Objective: To assess the relationship between AE Prevalence, Patient Safety Culture and Patient Safety Perception. Method: Cross-sectional, ex post facto comparative study on a single sample of patients. The prevalence and severity of adverse events were measured through a review of medical records (using the Modular Review Form (MRF2). Healthcare professional patient safety culture was determined using the Hospital Survey on Patient Safety Culture (HSOPSC) and patient perception of safety through the Hospital Care Safety Perceptions Questionnaire (HCSPQ). Correlation tests were used to compare the three dimensions. Population: 556 medical records and patients were studied for the prevalence and patient safety perception study, and 397 of the healthcare providers involved in the care of these patients were surveyed for the patient safety culture study, at 2 public and 2 private hospitals. Results: An inverse association was observed between AE prevalence and its severity and Patient Safety Culture Index (rho=-0.8) and Patient Safety Perception Index (rho=-0.6). No association was identified between Patient Safety Culture and Patient Safety Perception (rho=0.0001). No statistical differences were identified by hospital type. Conclusions: The joint analysis of AEP, PSC and PSP, in the same sample, offers an interesting and useful perspective on the associations between the variables studied; no correlation pattern was observed between the variables.

Favorable Immunologic Response Profile to Recombinant Thrombin Application in Surgery: An Integrated Analysis of 8 Clinical Trials

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4088-4088
Author(s):  
William Chapman ◽  
Kenneth Renkens ◽  
Richard Gamelli ◽  
Carlton Randleman ◽  
Jeffrey Ballard ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Phase 1 ◽  
Safety Information ◽  
Integrated Analysis ◽  
Immunologic Response ◽  
Available N ◽  
Post Surgery ◽  
Incision Site ◽  
Response Profile

Abstract Recombinant thrombin (rThrombin) is an active topical hemostat approved by the FDA as an aid to hemostasis. Treatment with thrombin derived from bovine sources has occasionally been associated with adverse events which appear to be related to the formation of antibodies against bovine thrombin and/or Factor V. The safety and immunogenicity of rThrombin have been evaluated in 8 clinical trials: 1 Phase 1 study, 5 Phase 2 studies, 1 randomized, double-blind Phase 3 study, and 1 open-label, single-group Phase 3b study. Pooled results from these trials provide a consistent and clinically relevant summary of safety information on the use of rThrombin in surgery. These trials utilized standardized data collection methods; more than 100 investigators from over 60 institutions participated. With 514 subjects treated with rThrombin in clinical trials to date (cut-off date July 2008), these results represent the largest safety database available for any commercially-available thrombin product. Standard safety measures were collected prior to surgery (baseline) through Day 29 post-surgery. Immunogenicity was evaluated at baseline and Day 29 using enzyme-linked immunosorbent assays and a time-to-clot assay to measure neutralizing potential of any detected anti-rThrombin antibodies. Of the subjects for whom data are currently available (N=514), 54% were male and 46% were female. Mean age was 57.0 years (SD, 15.7; range, 12–89 years). The following surgery types were represented: spine, 32% of patients; liver, 14%; peripheral arterial bypass, 23%; arteriovenous graft, 18%; burn, 12%. The median dose of rThrombin was 10,000 IU (range, 1000–50,000 IU). Topical application of rThrombin was well tolerated by study subjects. Common adverse events (AEs; reported by ≥10% of subjects) were similar regardless of surgery type and were consistent with the post-surgical setting. Common AEs included incision site complication, procedural pain, nausea, constipation, pyrexia, anemia, vomiting, insomnia, incision site pain, and pruritus. No single serious adverse event type occurred in &gt;1% of patients. Twelve of 514 subjects (2.3%) had anti-rThrombin product antibodies at baseline, a finding that is consistent with reports of antibodies to other recombinant forms of endogenous proteins. None of the 12 subjects with anti-rThrombin product antibodies at baseline had a change in titer ≥1.0 unit at Day 29. Among subjects who did not have anti-rThrombin product antibodies at baseline, 5/502 (1.0%) had detectable antibodies at Day 29. In total, 5/514 subjects (1.0%) were antibody positive at Day 29. None of the antibodies neutralized native human thrombin. These clinical studies, enrolling 514 subjects to date, collectively demonstrate that rThrombin is well-tolerated and has a favorable immunologic response profile when used in numerous surgical settings.

scholarly journals Maternal Perceptions of the Experience of Attempted Labor Induction and Medically Elective Inductions: Analysis of Survey Results from Listening to Mothers in California

2019 ◽  
Author(s):  
Eugene Declercq ◽  
Candice Belanoff ◽  
Ronald Iverson
Keyword(s):  
Medical Records ◽  
Medical Intervention ◽  
Study Data ◽  
Labor Induction ◽  
Cesarean Birth ◽  
Cesarean Births ◽  
Survey Results ◽  
Maternal Preference ◽  
First Time ◽  
The Relationship

Abstract Background The rate of induction of labor in the U.S. has risen from 9.6% in 1990 to 25.7% in 2017, including 31.7% of first-time births. Recent studies that have examined inductions have been small qualitative studies or relied on either medical records or administrative data. This study examines induction from the perspective of those women who experienced it, with a particular focus on the prevalence and predictors of inductions for nonmedical indications, women’s experience of pressure to induce labor and the relationship between the attempt to medically initiate labor and cesarean section. Methods Study data are drawn from the 2,119 women in the Listening to Mothers in California survey who were planning to have a vaginal birth in 2016. Mothers were asked if there had been an attempt to medically initiate labor, if it actually started labor, if they felt pressured to have the induction, if they had a cesarean and the reason for the induction. Reasons for induction were classified as either medically indicated or elective. Results Almost half (47%) of our respondents indicated an attempt was made to medically induce their labor, and 71% of those attempts initiated labor. More than a third of the attempts (37%) were elective. Attempted induction was most strongly associated with giving birth at 41+ weeks (aOR 3.28; 95% C.I. 2.21-4.87). Elective inductions were more likely among multiparous mothers and in pregnancies at 39 or 40 weeks. The perception of being pressured to have labor induced was related to higher levels of education, maternal preference for less medical intervention in birth, having an obstetrician compared to a midwife and gestational ages of 41+ weeks. Cesarean births were no more likely in the case of elective inductions. Cesarean birth was more likely in the case of induction (aOR 1.51; 95% C.I. 1.11-2.07) and especially following a failed attempt at labor induction (aOR 4.50; 95% C.I. 2.93-6.90). Conclusions Clinicians counselling mothers concerning the need for labor induction should be aware of mothers’ perceptions about birth and engage in true shared decision making in order to avoid the maternal perception of being pressured into labor induction.

scholarly journals Bispecific T-Cell Engager (BiTE) Antibody Based Immunotherapy for Treatment of Relapsed Refractory Multiple Myeloma (RRMM): A Systematic Review of Preclinical and Clinical Trials

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5567-5567
Author(s):  
Zunairah Shah ◽  
Mustafa Nadeem Malik ◽  
Syeda Sabeeka Batool ◽  
Sravanthi Kotapati ◽  
Aisha Akhtar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
T Cell ◽  
Adverse Events ◽  
Phase 1 ◽  
Serious Adverse Events ◽  
Myeloma Cells ◽  
Preclinical Trials ◽  
Bispecific T Cell Engager

Introduction Bispecific T-cell engager (BiTE) antibodies represent a novel therapeutic option for patients with multiple myeloma (MM). BiTE antibodies lack Fc region, and have variable domain only, they can simultaneously bind to two different epitopes i.e. cluster of differentiation 3 (CD3) molecules on tumor-specific T cells, and a specific antigen on myeloma cells, which leads to T-cell dependent destruction of myeloma cells. Currently, blinatumomab, specific for CD3 and CD19 is the only Food and Drug Administration FDA approved BiTE antibody for clinical use in patients with relapsed/refractory (RR) B-cell acute lymphoblastic leukemia, several similar BiTE antibodies are under development. Methods Following PRISMA guidelines, we performed comprehensive literature on 4/15/19 cross-referencing the terms "bispecific antibodies" and "multiple myeloma" using PubMed, Embase, Web of Science, Cochrane Library, Clinicaltrials.gov and review of international medical meeting abstracts. Initially, 256 articles were identified and after detailed scrutiny, one phase 1 clinical trial with prelim results, 4 preclinical and 4 ongoing clinical trials were included. Results Preclinical trials: Anti-BCMA x Anti-CD3 Bispecific Antibody: BiTE antibodies are still in early development in MM, and most of the published data is about the pre-clinical phase. In preclinical trials, Hipp et al. 2017 and Cho et al. 2018 reported that AMG 420 (BI 836909) and AMG 701, which are anti CD3 and B-cell maturation antigen (BCMA), are highly efficacious in vitro in the killing of myeloma cells and potently induces autologous tumor cell lysis in patients with both newly diagnosed and RRMM regardless of their disease status. In mouse xenograft models reconstituted with human T cells, in vivo efficacy of AMG 420 was reported with an overall response in 6 of 10 animals, with all 6 responders became tumor-free at the end of the study. In an orthotopic L-363 xenograft model, treatment with AMG 420 resulted in prolonged median survival of 43-43.5 days. Dilillo et al. 2018 and Ji Li et al. 2017 reported similar in vivo results for REGN5458 and BFCR4350A respectively. Clinical trials: Currently, there are 5 phase 1 ongoing clinical trials (Table 1). Updated results of only first in human phase I AMG 420 are available. Forty-two MM patients with a high tumor burden and four prior lines of therapy were given 2.5 treatment cycles with AMG 420. Overall thirteen (31%) patients responded to AMG 420 therapy, with complete response (CR) in 6 (14.2%) patients, very good partial response (VGPR) in 2 (5%) patients and partial response (PR) in 2(5%) patients. Eleven of these patients responded in the first treatment cycle, with a median response time of 1 month. Twenty-five (57.1%) patients discontinued treatment due to progressive disease. Four deaths were reported; 2 from disease progression and 2 due to adverse events; neither of them was treatment-related. Serious adverse events were reported in twenty-one (50%) patients, the infection was reported in twelve (29%) and polyneuropathy in three (7%), eighteen (43%) required hospitalization. Treatment-related serious adverse events included three (7%) patients with grade 2-3 cytokine release syndrome, three (7%) with polyneuropathy and one (2.3%) with edema. Conclusion After the success of naked antibodies like daratumumab and elotuzumab for MM, there is a need to develop immunotherapy using conjugated antibodies and BiTE antibodies to overcome the challenge of MM resistance and relapse to prior therapies. Preclinical data with BiTE antibodies are promising; AMG 420 anti-CD3/BCMA BiTE has already been granted fast track status by the FDA. We anticipate that drug will enter phase 2 clinical trials for drug development against RRMM Other BiTE antibodies with strong preclinical efficacy are under development and data from larger prospective clinical trials is needed to explore their efficacy in the treatment of multiple myeloma. Table 1 Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

scholarly journals The Safety of Novel Drugs Targeting Factor XI and XII in Human Clinical Trials:a Systematic Review

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4966-4966
Author(s):  
Gillian E Mair ◽  
Sven Reid Olson ◽  
Joseph J Shatzel
Keyword(s):  
Monoclonal Antibody ◽  
Clinical Trials ◽  
Adverse Events ◽  
Dose Escalation ◽  
Phase 1 ◽  
Postoperative Bleeding ◽  
Phase 2 ◽  
Risk Of Bleeding ◽  
Novel Drugs ◽  
Contact Pathway

Introduction While effective at treating and preventing thrombosis, modern forms of anticoagulation universally increase the risk of hemorrhage. Data suggests that factors FXI and FXII could serve as druggable targets to provide anticoagulation without increasing the risk of bleeding. The purpose of this systematic review is to evaluate the safety of novel drugs targeting FXI and FXII in human clinical trials. Methods We performed a search in Ovid MEDLINE to identify published manuscripts describing administration of contact pathway-inhibiting drugs to humans. All human clinical trials evaluating a drug specific to FXI or FXII were included. Outcomes of interest collected for analysis included primarily bleeding events of any type, total adverse events (AEs)as well as other treatment-emergent adverse events (TEAE) and treatment-related adverse events (TRAE). Results A total of 338 published articles were identified from the original search. After screening, one phase 2 study of an antisense oligonucleotide (ISIS 416858) and three phase 1 trials of monoclonal antibodies (AB023, BAY1213790, MAA868) were included. A total of 465 patients across these 4 clinical trials were included. No patients experienced spontaneous bleeding. Postoperative bleeding occurred in 3% of patients treated with ISIS 416858 at each dose level and one patient experienced major bleeding. For comparison an 8% postoperative bleeding rate was seen in the arm treated with prophylactic low molecular weight heparin (LMWH). AB023, a monoclonal antibody inhibiting FXIIa-mediated activation of FXI to FXIa, was examined in a phase 1, dose-escalation trial in 21 healthy adults. Overall, there were no severe AEs. Minor AEs occurred in 10 of the 21 patients. 3 patients were deemed to possibly have TRAE. There was no statistical difference in bleeding time compared to placebo. activated thromboplastin time (aPTT) was prolonged for over a month after the highest dose level. BAY1213790 is a monoclonal antibody targeting the enzymatic active site of FXIa, and was studied in a phase 1 dose escalation trial in 83 healthy men. There were no severe AEs. Of the 54 subjects experiencing AEs, 34 were mild and 20 were moderate. TRAE were reported in 6 subjects. One subject had an infusion reaction and another subject requested the infusion be stopped. APTT showed a dose-dependent increase while bleeding times also did not increase compared to placebo. ISIS 416858 is an antisense oligonucleotide targeting FXI mRNA for degradation at its source within the hepatocyte. ISIS416858 was studied in a phase 2, randomized controlled trial in patients undergoing total knee arthroplasty. The safety and efficacy at preventing post-operative venous thromboembolism (VTE) was assessed at 200 mg or 300 mg doses compared to standard-of-care with LMWH. Bleeding occurred in 4 (3%), 2 (3%), and 6 (8%) patients in these three study groups, respectively. This was the only study drug where one patient experienced major bleeding. Mild AEs affected 219 subjects, with severe AEs occurring in 4 patients; only 2 discontinued ISIS416858. Patients in the 300 mg dose cohort of ISIS416858 experienced statistically fewer VTE events compared with LMWH; bleeding rates were numerically low compared to LMWH (3% vs 8%), though statistical significance was not reached. MAA868 is a monoclonal antibody targeting both the zymogen and active forms of FXI at the enzymatic active site, and was studied in a phase 1, dose-escalation clinical trial. MAA868 is unique due to its subcutaneous route of administration. Of the total 61 patient cohort, 34 patients experienced AEs and 9 TRAE. Only 2 severe, unrelated AEs occurred after the trial: one fatal cardiac arrest after elective surgery, and a gunshot wound requiring urgent surgery. MAA868 resulted in prolonged FXI suppression for up to four weeks. Conclusion Contact pathway-inhibiting drugs show promise as novel anticoagulation strategies that could significantly reduce the risk of bleeding seen with traditional anticoagulants. Additional studies are needed to further develop these drugs to test their efficacy at targeting the coagulation pathway in common settings of high risk for VTE, or existing thrombosis. The paradigm that anticoagulants cause bleeding could be broken in the near future based on this promising clinical data on contact pathway inhibition. Table Disclosures Shatzel: Aronora, Inc.: Consultancy.

Continuous infusion of apomorphine in a series of thirty patients with parkinson's disease

2019 ◽  
pp. 43-47 ◽  
Author(s):  
Rezzak Yılmaz ◽  
Çağlar Sarılar ◽  
Cenk Akbostancı
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Adverse Events ◽  
Medical Records ◽  
Motor Fluctuations ◽  
Motor Complications ◽  
Subcutaneous Nodules ◽  
Disease Characteristics ◽  
Deep Brain

Apomorphine is a dopamine agonist primarily used for the treatment of motor fluctuations and severe dyskinesias in late – stage Parkinson’s Disease. We retrospectively studied medical records of 30 patients who were on continuous apomorphine infusion treatment. They were evaluated for their disease characteristics, satisfaction for the therapy and adverse events. Results showed that 17 patients were satisfied with the therapy. The main reason of cessation of therapy (15 patients) was subthalamic nucleus deep brain stimulation. Arrythmia and subcutaneous nodules were relatively rare (3 patients). Results were compared with similar studies. Apomorphine therapy appears as a safe option for patients with motor complications and cognitive or neuropsychiatric problems.

Integration of supportive care in immuno-oncology trials: Investigating the incidence and severity of immune-related toxicities among older adults versus mid-age patients on immunotherapy-based phase I clinical trials.

2017 ◽  
Vol 35 (31_suppl) ◽  
pp. 152-152
Author(s):  
Ishwaria Mohan Subbiah ◽  
Kenneth R. Hess ◽  
Takeo Fujii ◽  
Anna Lui ◽  
Vivek Subbiah ◽  
...  
Keyword(s):  
Older Adults ◽  
Clinical Trials ◽  
Adverse Events ◽  
Supportive Care ◽  
Phase I ◽  
Phase 1 ◽  
Low Grade ◽  
Phase I Trials ◽  
High Grade ◽  
Phase I Clinical Trials

152 Background: Older adults (65y+) with cancer are underrepresented in trials of novel drugs notably in phase I clinical trials with immunotherapies. The trepidation over immune-related toxicities in the context of older age and associated comorbidities may function as a barrier to participation. To that end, we investigated the enrollment and incidence of immune related adverse events of older adults enrolled in phase 1 immunotherapy trials. Methods: We identified 422 consecutive pts w advanced cancer treated on immunotherapy-based phase I trials bw 04/2009-09/2015, and collected pt/disease characteristics and immune-related adverse events (irAE) such as endocrinopathies, diarrhea/colitis, pneumonitis, constitutional (fatigue, fever, anorexia), myalgia, and dermatitis. Results: Older adults comprised 27% of trial participants (116 of 422 pts, median age 70y) while 256 pts were mid age (61%, median 56y). Most common cancers were GI (n = 108, 26%), thoracic/head/neck (n = 84, 20%), GU (n = 54, 13%), and GYN (n = 47, 11%). Median PFS was comparable among older pts (2.4m) and mid age (2.1m). Older adults had a higher incidence of irAE than mid age (low grade [G1/2] 49% vs 34%, p 0.02; high grade [G3/4] 19% vs 11%. p 0.14). The odds ratio of high grade events among older adults vs mid age pts was 1.81 (95% CI 1.01, 3.24; p 0.05) and low grade events was 1.85 (95% CI 1.20, 2.85; p 0.0055). Most common G1/2 irAE among all patients was fatigue (n = 76, 18%), dermatitis (n = 59, 14%), fever (n = 29, 7%) and anorexia (n = 28, 7%) with older adults having a greater incidence of low grade fatigue (25% vs 15%, OR 1.84, 95% CI 1.09, 3.10, p 0.025). Conclusions: Older adult participation remained under 30% for immunotherapy-based phase I trials. This early analysis suggests a higher incidence of toxicities among older adults, which calls for the urgent integration of comprehensive supportive care strategy to guide seniors through therapy. This work lays the foundation for future studies investigating the early involvement of supportive care through treatment on early phase clinical trials with immunotherapeutic agents.

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