Evaluation of hypersensitivity reactions to oxaliplatin in gastrointestinal malignancies.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 709-709 ◽  
Author(s):  
Kelly Markey ◽  
Tyra Gatewood ◽  
Tiffany Valone ◽  
Jonathan R. Strosberg
Keyword(s):  
Adverse Event Reporting System ◽  
Treatment Strategies ◽  
Case Series ◽  
Adverse Event Reporting ◽  
Hypersensitivity Reactions ◽  
Success Rates ◽  
Gastrointestinal Malignancies ◽  
Grade 3 ◽  
Patients Experience ◽  
To Receive

709 Background: Oxaliplatin is an important component of therapy for multiple gastrointestinal cancers. The incidence of hypersensitivity reaction (HSR) to oxaliplatin is approximately 10%, and about 3% are serious in nature (Grade 3 or 4). Data on management of hypersensitivity reactions is limited to small case series, with scarce information on the success rates of rechallenging patients who have previously reacted. Methods: We conducted a retrospective review of patients who had a documented hypersensitivity (HSR) to oxaliplatin utilizing our internal adverse event reporting system from January 1, 2007 until December 31, 2012. Results: 44 patients met inclusion criteria for this study. The majority had a grade 1 or 2 reaction (n = 36 or 81.82%). Seven patients had a grade 3 reaction and one patient experienced a grade 4 reaction. 29 patients were rechallenged with oxaliplatin during subsequent courses. Infusion durations were extended in 79% of cases, and additional premedications were administered in 90%. Two patients were treated with a desensitization protocol, which consisted of serial dilutions of oxaliplatin (given over approximately 8 hours) with a two-stage premedication regimen. With these measures, seventeen of the twenty-nine patients (66%) were able to receive 3 or more additional infusions, thirteen (45%) received 5 or more additional infusions, and 4 (14%) we able to receive 10 or more additional infusions. Conclusions: Our review of hypersensitivity reactions to oxaliplatin demonstrates that the majority of patients experience mild (Grade 1 or 2) reactions and are able to be successfully rechallenged in subsequent courses with modifications in the infusion rate and premedications. The use of these treatment strategies may prevent premature discontinuation of an important backbone drug for the treatment of gastrointestinal malignancies.

Sirolimus plus prednisolone vs sirolimus monotherapy for kaposiform hemangioendothelioma: a randomized clinical trial

Blood ◽  
2022 ◽  
Author(s):  
Yi Ji ◽  
Siyuan Chen ◽  
Jiangyuan Zhou ◽  
Kaiying Yang ◽  
Xuepeng Zhang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Primary Outcome ◽  
Treatment Strategies ◽  
Platelet Response ◽  
Kaposiform Hemangioendothelioma ◽  
Total Incidence ◽  
Short Course ◽  
Life Threatening ◽  
Grade 3 ◽  
To Receive

The Kasabach-Merritt phenomenon (KMP) in kaposiform hemangioendothelioma (KHE) is characterized by life-threatening thrombocytopenia and consumptive coagulopathy. This study compared the efficacy and safety of sirolimus plus prednisolone versus sirolimus monotherapy as treatment strategies for KHE with KMP in the largest cohort to date. Participants were randomized to receive either sirolimus in combination with a short course of prednisolone or sirolimus monotherapy for at least 12 months. The primary outcome was defined as achievement of a durable platelet response (platelet count >100×109/L) at week 4. Participants completed efficacy assessments 2 years after the initial treatment. At week 4, a durable platelet response was achieved by 35 of 37 patients given sirolimus and prednisolone compared with 24 of 36 patients given sirolimus monotherapy (difference 27.9%; 95% CI, 10.0% to 44.7%). Compared with the sirolimus monotherapy group, the combination treatment group showed improvements in terms of measures of durable platelet responses at all points during the initial 3-week treatment period, median platelet counts during weeks 1 to 4, increased numbers of patients achieving fibrinogen stabilization at week 4, and objective lesion responses at month 12. Patients receiving combination therapy had fewer blood transfusions and a lower total incidence of disease sequelae than patients receiving sirolimus alone. The frequencies of total adverse events and grade 3-4 adverse events during treatment were similar in both groups. The responses seen in patients with KHE with KMP were profound and encouraging, suggesting that sirolimus plus prednisolone should be considered a valid treatment for KHE with KMP. ClinicalTrial.gov, number NCT03188068

scholarly journals Case series of reports of pruritus and sipuleucel-T submitted to the Food and Drug Administration Adverse Event Reporting System

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Graça M. Dores ◽  
Silvia Perez-Vilar ◽  
Manette T. Niu
Keyword(s):  
Adverse Event ◽  
Drug Administration ◽  
Reporting System ◽  
Food And Drug Administration ◽  
Adverse Event Reporting System ◽  
Package Insert ◽  
Case Series ◽  
Adverse Event Reporting ◽  
Cellular Immunotherapy ◽  
Event Reporting

AbstractSipuleucel-T, an autologous active cellular immunotherapy, is indicated for the treatment of asymptomatic or minimally symptomatic castration-resistant prostate cancer. The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) received a report of pruritus without rash following the second dose of sipuleucel-T in a patient who had otherwise not started any new medications concurrent with the first and second doses of sipuleucel-T. No further sipuleucel-T was administered, but symptoms persisted for at least 6 weeks despite treatment with several medications aimed at symptomatic relief of pruritus. Rash is the only dermatologic adverse event included in the sipuleucel-T U.S. package insert. A search of the FAERS database yielded seven additional U.S. reports of pruritus and sipuleucel-T identified as the primary suspect medication; two of these occurred prior to the administration of sipuleucel-T (following leukapheresis). In data mining analyses, pruritus following sipuleucel-T was not reported more frequently than expected when compared to all other adverse event-drug/biologic combinations in FAERS. Thus, pruritus following sipuleucel-T administration was rarely, but not disproportionately, reported to FAERS. Although we cannot exclude the possibility that diabetes, malignancy, or other conditions may have contributed to pruritus in our index patient, in view of the timing of sipuleucel-T therapy and onset of symptoms, a drug/biologic-related reaction is plausible. In the appropriate clinical scenario, sipuleucel-T (or its components) should not be overlooked as a potential etiological agent in pruritus.

scholarly journals Effects of the COVID-19 pandemic on publication landscape in chimeric antigen receptor-modified immune cell research

2021 ◽  
Author(s):  
Jianhua Yu ◽  
Ahmet Yilmaz
Keyword(s):  
Clinical Trials ◽  
Cancer Immunotherapy ◽  
Immune Cell ◽  
Adverse Event Reporting System ◽  
Data Entry ◽  
Clinical Results ◽  
Adverse Event Reporting ◽  
Original Research ◽  
Antigen Receptors ◽  
Success Rates

Chimeric antigen receptors (CARs) are artificial receptors introduced mainly into T cells. CAR-induced immune cell (CARi) products have achieved impressive success rates in treating some difficult-to-treat hematological malignancies. Here, we describe effects of the global COVID-19 pandemic on CARi publication landscape. Due to the pandemic, the total number of publications decreased in 2020 compared to 2019 in all fields of cancer immunotherapy except CARi. Nearly exponential increases in the number of CARi publications slowed-down in 2020 for the first time in the past 11 years. There were more CARi than coronavirus publications until 2020 when coronavirus publications increased over 5,000% compared to 2019 (575 publications in 2019 vs. 30,390 in 2020). Unlike cancer immunotherapy where the majority of the publications consist of conference abstracts and review articles, majority of the coronavirus publications are original research articles. There are more coronavirus publications in Pubmed than Embase. The opposite is true for CARi publications. Our analysis of the data from the FDA Adverse Event Reporting System (FAERS) show significantly higher death rate in patients treated with Kymirah than Yescarta (28.14% vs. 16.02%). Kymirah and Yescarta are the two main CAR T cell products for treatment of DLBCL and/or B-ALL. However, despite being highly significant, this result is not easily interpretable due to multiple confounding variables in the FAERS data. Our analysis additionally suggest that the significant effects of co-stimulatory domains (4-1BB vs. CD28) consistently reported in preclinical studies do not translate into clinical results. Our manual curation of the CARi publications in PubMed shows that only 5.2% of the publications report results from CARi clinical trials, although we found 663 clinical trials listed on ClinicalTrials.gov database. In conclusion, publication landscape in CARi as well as other fields of cancer immunotherapy has changed due to the global COVID-19 pandemic. This trend will likely continue in the near future. CARi research is now in need of increased measures by publishers to reduce repetitive and/or duplicate publications and more stringent criteria for data entry into public databases including PubMed, Embase, ClinicalTrials.gov, and FAERS to advance this important field of medical research.

Finasteride and Suicide: A Postmarketing Case Series

Dermatology ◽  
2020 ◽  
Vol 236 (6) ◽  
pp. 540-545 ◽  
Author(s):  
Michael S. Irwig
Keyword(s):  
Adverse Event ◽  
Small Sample Size ◽  
Adverse Event Reporting System ◽  
Medication Use ◽  
Case Series ◽  
Relevant Information ◽  
Adverse Event Reporting ◽  
Small Sample ◽  
Androgenic Alopecia ◽  
Medication Discontinuation

<b><i>Background:</i></b> In 2011, depression was added to the product labeling of finasteride in the USA. The US Food and Drug Administration’s Adverse Event Reporting System database contains at least 36 death cases for finasteride. The aim of this study is to characterize the clinical histories and symptoms reported by a series of 6 suicide victims who took finasteride for treatment of androgenic alopecia. <b><i>Methods:</i></b> Medical records and autopsy reports were provided by family members of the cases. Relevant information was extracted according to guidelines for submitting adverse event reports. <b><i>Results:</i></b> An important pattern of symptoms was common among all cases who committed suicide in the setting of finasteride use – insomnia and persistent sexual dysfunction after medication discontinuation. Insomnia and fatigue/tiredness were some of the most debilitating symptoms. Apart from 1 case who had hyperlipidemia, there was no documentation of concomitant medication use with finasteride or any baseline medical or psychiatric diagnoses prior to starting finasteride. The findings of this postmarketing series may not be generalizable to the population of men who committed suicide in the setting of finasteride use due to small sample size and bias. Associations between medication use and symptoms cannot prove causality. <b><i>Conclusion:</i></b> Men under the age of 40 who use finasteride for alopecia are at risk for suicide if they develop persistent sexual adverse effects and insomnia. Further research is needed to establish whether finasteride has a causal relationship to suicide.

scholarly journals Pruritus after discontinuation of cetirizine

2019 ◽  
Vol 10 ◽  
pp. 204209861985999
Author(s):  
Amy H. Chung ◽  
Lois La Grenade ◽  
Lisa M. Harinstein
Keyword(s):  
Adverse Event ◽  
Medical Literature ◽  
Adverse Event Reporting System ◽  
Healthcare Providers ◽  
Case Series ◽  
Adverse Event Reporting ◽  
Outcome Information ◽  
Intense Pruritus ◽  
Urticaria Treatment ◽  
Time To Onset

Background: Intense pruritus or itching emerging after discontinuation of cetirizine has been the subject of postmarketing reports submitted to the U.S. Food and Drug Administration (FDA), published in the medical literature, and discussed on the internet. To better understand and further investigate this adverse event, we analyzed cases of pruritus occurring after discontinuation of cetirizine in the FDA Adverse Event Reporting System (FAERS) database and medical literature. Methods: We conducted a retrospective study to identify and describe cases of pruritus occurring after discontinuation of cetirizine in the FAERS database and medical literature through April 24, 2017. Data collected from the reports included demographic information, reason for use, serious outcome, report source, duration of cetirizine use, time to onset of pruritus after cetirizine discontinuation, presence of associated urticaria, treatment for pruritus, concomitant comorbidities and medications associated with pruritus, rechallenge information, and patient outcome information. Results: We identified 146 cases of pruritus after discontinuation of cetirizine. Reporting frequency increased starting in 2008. The median patient age was 38 years ( n = 141), ranging from 6 to 71 years, and cases were predominantly reported in females ( n = 110). Most cases ( n = 115) were submitted directly to the FDA from consumers or healthcare providers. The median duration of use of cetirizine prior to discontinuation was 24 months ( n = 130), ranging from 0.3 to 172.2 months. The median time to onset of pruritus from discontinuation was 2 days ( n = 91), ranging from 0.5 to 5 days. Of the 55 cases that reported discontinuation of cetirizine again after restarting, 54 reported pruritus recurrence. Conclusions: Our case series provided evidence of an association between the discontinuation of cetirizine and the development of pruritus. The mechanism by which cetirizine causes pruritus upon discontinuation is unknown. Patients and prescribers should have knowledge of this adverse event, given the widespread use and availability of cetirizine, and potential impact on patient quality of life.

Subacute Thrombotic Events Associated with Drug Eluting Cardiac Stents May Be Localized Hypersensitivity Reactions to Polymers.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2198-2198
Author(s):  
Charles Bennett ◽  
Jonathan Nebeker ◽  
Renu Virmani ◽  
June McKoy ◽  
Jenny Hoffman ◽  
...  
Keyword(s):  
Stent Implantation ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
World Health ◽  
Entire Body ◽  
Hypersensitivity Reactions ◽  
Cardiac Events ◽  
Skin Reactions ◽  
Permanent Disability ◽  
Drug Eluting

Abstract Background: In October 2003, six months after approval of the first drug-eluting coronary stent (CYPHER™ stent), the FDA reported 50 stent-associated hypersensitivity reactions. In November 2003, FDA officials reported that these reactions were probably due to concomitantly prescribed medications. Methods: All adverse device event reports for CYPHER stent associated hypersensitivity- reactions in the FDA’s adverse event reporting system, the published literature, or from RADAR, between April 2003 and June 2004 were reviewed. Causality was evaluated using World Health Organization criteria. Results: Review of FDA reports (n=2,607) identified 161 persons with hypersensitivity symptoms. Fewer than 20 hypersensitivity cases were reported monthly, except for 43 and 42 reports in October and November 2003. Symptoms began within 2 days of stent implantation (21%), between 2 and 7 days (43%) and between 7 and 14 days (19%) following stent implantation and persisted for less than 8 days for 17%, 8–30 days for 29% and > 30 days for 55%. Findings included rash (80%), itching (28%), hives (19%), dyspnea (12%), fever (12%), chest pain (8%), anaphylaxis (7%), joint pain or swelling (7%) and high or low blood pressure (5%). Among persons with rashes, 25% covered the entire body, 21% developed hives, 7% had localized maculopapular eruptions and 4% developed blisters or desquamation. Treatment included emergency interventions (26%) or hospitalization (19%). Outcomes included permanent disability (5%) or death (2%). Aspirin or clopidogrel was discontinued at the time of hypersensitivity onset for 42. Using WHO criteria, clopidogrel, aspirin, ticlopidine and/or the stent itself were classified as possible causes for > 85% of cases. Of 150 events possibly caused by the CYPHER stent, 35 persisted for > 30 days. For 7 probable CYPHER-stent induced hypersensitivity cases identified by RADAR (n=4), the FDA (n=2) or the literature (n=1), symptom onset was < 5 days (n=3) and at 3 weeks, 1 month, 4 months, and 7 months after stent implantation. Findings included rash (n=4), hives (n=1), blisters on both hands (n=1), dyspnea (n=2), eosinophilia (n=1), elevated IgE levels (n=2) and Gallium-67 scan findings at the stent (n=1). Findings did not abate with thienopyridine discontinuation (n=5). Outcomes included resolution of symptoms with hospitalization (n=1) or corticosteroids (n=2), persistent angina (n=1) and subsequent occurrence of fatal cardiac events, with autopsy identification of eosinophilic infiltrates at the stent site (n= 2 patients). Conclusion: Rash, hives, dyspnea and catastrophic cardiac events may represent local and systemic hypersensitivity reactions from the CYPHER-stent. Reporting of these events decreased by > 90% following a FDA advisory that suggested that skin reactions were unrelated to the stent. However, our findings highlight the importance of continued vigilance for hypersensitivity reactions that may represent an early manifestation of a catastrophic hypersensitivity event.

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