scholarly journals 699. Hepatobiliary Safety in Adults With Community-Acquired Bacterial Pneumonia (CABP) Treated With Lefamulin (LEF) or Moxifloxacin (MOX): Pooled Analysis of Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 Study Results

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S316-S316 ◽  
Author(s):  
James H Lewis ◽  
Anita F Das ◽  
Daniel Stein ◽  
Steven P Gelone ◽  
Jennifer Schranz
Keyword(s):  
Total Bilirubin ◽  
Severe Disease ◽  
Pooled Analysis ◽  
System Organ Class ◽  
Chronic Injury ◽  
Time To Peak ◽  
Noninferiority Trials ◽  
Study Results ◽  
Hy’S Law ◽  
End Stage

Abstract Background LEF efficacy and safety were shown in 2 noninferiority trials (LEAP 1/2) vs. MOX in adults with CABP. We assessed the hepatobiliary safety of LEF based on pooled analyses of LEAP 1/2 data. Methods In LEAP 1, PORT III–V patients received LEF 150 mg IV q12h for 5–7 days or MOX 400 mg IV q24h for 7 days, with optional IV-to-oral switch (600 mg LEF q12h or 400 mg MOX q24h). In LEAP 2, PORT II–IV patients received oral LEF 600 mg q12h for 5 days or oral MOX 400mg q24h for 7 days. Exclusion criteria included infection with HBV/HCV, acute hepatitis, cirrhosis, AST or ALT >5xULN, total bilirubin >3xULN (unless Gilbert’s disease), AST or ALT >3xULN and total bilirubin >2xULN, and manifestation of end-stage liver disease. Hepatic safety was assessed from baseline (BL) and multiple post-BL blood samples using a central laboratory, TEAEs, and expert consultant adjudication. Pooled analyses included all randomized/treated patients (safety population). Results Of 1282 randomized/treated patients, 1251 had BL and post-BL hepatobiliary data (table). Post-BL distribution of ALT/AST was generally similar for both groups, although ALT >AST in the absence of muscle injury or alcohol use. Overall, rates of patients experiencing an increase in ALT/AST >3xULN, ALP >2xULN, or total bilirubin >1.5xULN were low (table). Patients with elevated vs. normal BL transaminases (TAs) were more likely to have post-BL elevations >3xULN, but the vast majority remained <5xULN. Among patients with ALT >5xULN, peak increases were generally seen in the first week after the first LEF dose and declined to within/near normal levels by late follow-up (day 28); for MOX, time to peak ALT was less consistent (figure). No LEF pt and 1 MOX pt met laboratory criteria for Hy’s Law. Elevations in TAs were reversible, with no evidence of chronic injury. The LEF injury pattern was predominantly hepatocellular (50.0%)/mixed (40.0%), with no apparent gender, age, or ethnic predominance. TEAEs in the hepatobiliary disorders system organ class were reported in 6 (0.9%) LEF patients and 6 (0.9%) MOX patients, with similar levels seen in patients with elevated BL TAs. There were no symptomatic patients, severe disease, or evidence of hypersensitivity. Conclusion Low incidences of hepatobiliary parameter elevations and TEAEs were observed, with no apparent differences between LEF and MOX. Disclosures All authors: No reported disclosures.

scholarly journals 2233. Efficacy and Symptom Resolution by Visit in Adults With Community-Acquired Bacterial Pneumonia (CABP) Treated With Lefamulin (LEF) or Moxifloxacin (MOX): Pooled Analysis of Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 Study Results

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S762-S763
Author(s):  
Jennifer Schranz ◽  
Anita F Das ◽  
Elizabeth Alexander ◽  
Gregory J Moran ◽  
Christian Sandrock ◽  
...  
Keyword(s):  
Clinical Response ◽  
Primary Endpoint ◽  
Study Drug ◽  
Antibiotic Use ◽  
Pooled Analysis ◽  
Success Rates ◽  
Symptom Resolution ◽  
Noninferiority Trials ◽  
Atypical Pathogens ◽  
Study Results

Abstract Background Efficacy and safety of LEF were shown in 2 noninferiority trials (LEAP 1/2) vs. MOX in adults with CABP. We assessed the efficacy of LEF by visit based on a pooled analyses of LEAP 1/2 data. Methods In LEAP 1, PORT III–V patients (patients) received LEF 150 mg IV q12h for 5–7 days or MOX 400 mg IV q24h for 7 days, with optional IV-to-oral switch (600 mg LEF q12h or 400 mg MOX q24h). In LEAP 2, PORT II–IV patients received oral LEF 600 mg q12h for 5 days or oral MOX 400 mg q24h for 7 days. Criteria for defining the FDA primary endpoint of early clinical response (ECR) at 96 ± 24 hours after first dose were applied to each visit through late follow-up (LFU; days 27–34) in the intent-to-treat (ITT; all randomized patients) population. Investigator assessment of clinical response (IACR) was examined at end of treatment (EOT; within 2 days after last dose), test-of-cure (TOC; 5–10 days after last dose; EMA primary endpoint), and LFU in the modified ITT (mITT; received ≥1 dose of study drug) and clinically evaluable (CE; met predefined evaluability criteria) populations. Results are presented by visit for pooled LEAP 1/2 data. Results 1289 ITT patients were randomized (LEF, n = 646; MOX, n = 643). Most patients in both groups achieved ECR at Day 3, with further increases through Day 7 and sustained efficacy through LFU (Fig 1). In mITT patients, IACR success rates at EOT/TOC/LFU were 87.1/85.0/83.2% with LEF and 88.1/87.1/86.1% with MOX; results were consistent in CE patients. The proportions of ITT patients with resolution of all baseline signs/symptoms of CABP increased similarly by visit in both treatment groups (Fig 2). Most patients did not achieve complete sign/symptom resolution until TOC, with fever generally being the first and cough the last to resolve. There was no apparent relationship between ECR and age, gender, renal status, SIRS, PORT, prior antibiotic use, baseline pathogens, typical/atypical pathogens, or mono/polymicrobial pathogens. The high percentage of patients at LFU with baseline symptom resolution suggests that symptom resolution was sustained. Conclusion In this pooled analysis, efficacy results were similar by visit in the LEF and MOX groups, with high ECR rates maintained through LFU. LEF will provide a potential new effective systemic monotherapy alternative to fluoroquinolones for the empiric treatment of CABP. Disclosures All authors: No reported disclosures.

scholarly journals Electrolyte imbalances in patients with severe coronavirus disease 2019 (COVID-19)

2020 ◽  
Vol 57 (3) ◽  
pp. 262-265 ◽  
Author(s):  
Giuseppe Lippi ◽  
Andrew M South ◽  
Brandon Michael Henry
Keyword(s):  
Weighted Mean Difference ◽  
Severe Disease ◽  
Total Sample ◽  
Pooled Analysis ◽  
Severe Form ◽  
Electrolyte Imbalance ◽  
Sodium Potassium ◽  
Impact Patient Care ◽  
Insight Into ◽  
Electrolyte Abnormalities

Background Early studies have reported various electrolyte abnormalities at admission in patients who progress to the severe form of coronavirus disease 2019 (COVID-19). As electrolyte imbalance may not only impact patient care, but provide insight into the pathophysiology of COVID-19, we aimed to analyse all early data reported on electrolytes in COVID-19 patients with and without severe form. Methods An electronic search of Medline (PubMed interface), Scopus and Web of Science was performed for articles comparing electrolytes (sodium, potassium, chloride and calcium) between COVID-19 patients with and without severe disease. A pooled analysis was performed to estimate the weighted mean difference (WMD) with 95% confidence interval. Results Five studies with a total sample size of 1415 COVID-19 patients. Sodium was significantly lower in patients with severe COVID-19 (WMD: –0.91 mmol/L [95% CI: –1.33 to –0.50 mmol/L]). Similarly, potassium was also significantly lower in COVID-19 patients with severe disease (WMD: –0.12 mmol/L [95% CI: –0.18 to –0.07 mmol/L], I2=33%). For chloride, no statistical differences were observed between patients with severe and non-severe COVID-19 (WMD: 0.30 mmol/L [95% CI: –0.41 to 1.01 mmol/L]). For calcium, a statistically significant lower concentration was noted in patients with severe COVID-19 (WMD: –0.20 mmol/L [95% CI: –0.25 to –0.20 mmol/L]). Conclusions This pooled analysis confirms that COVID-19 severity is associated with lower serum concentrations of sodium, potassium and calcium. We recommend electrolytes be measured at initial presentation and serially monitored during hospitalization in order to establish timely and appropriate corrective actions.

scholarly journals Immunosuppressants in Liver Transplant Recipients With Coronavirus Disease 2019: Capability or Catastrophe?—A Systematic Review and Meta-Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Dipesh Kumar Yadav ◽  
Vishnu Prasad Adhikari ◽  
Qi Ling ◽  
Tingbo Liang
Keyword(s):  
Liver Transplant ◽  
Immunosuppressive Therapy ◽  
Meta Analysis ◽  
Severe Disease ◽  
Random Effect ◽  
Random Effect Model ◽  
Mammalian Target Of Rapamycin ◽  
Calcineurin Inhibitors ◽  
Pooled Analysis ◽  
Organ Rejection

Background: The probable impact of a maintenance immunosuppressant (IS) on liver transplant (LT) recipients with coronavirus disease 2019 (COVID-19) remains unexplored. Our specific aim was to approximate the prognosis of LT recipients with COVID-19 on the standard maintenance IS.Method: We searched separate databases for the qualified studies in between December 2019 and June 25, 2021. Ultimately, a meta-analysis was carried out using a fixed-effect or random-effect model based on the heterogeneity.Results: In a total of eight studies and 509 LT recipients with COVID-19, the pooled rates of severity and mortality during all the combined immunosuppressive therapies were 22.4 and 19.5%, respectively. Our study sufficiently showed that an immunosuppressive therapy in LT recipients with COVID-19 was significantly associated with a non-severe COVID-19 [odds ratio (OR): 11.49, 95% CI: 4.17–31.65; p &lt; 0.001] and the survival of the patients (OR: 17.64, 95% CI: 12.85–24.22; p &lt; 0.001). Moreover, mammalian target of rapamycin inhibitor (mTORi) typically had the lowest rate of severity and mortality compared to other ISs such as calcineurin inhibitors (CNIs), steroids, and antimetabolites, i.e., severity (13.5 vs. 21.1, 24.7, and 26.3%) and mortality (8.3 vs. 15, 17.2, and 12.1%), respectively. Contrary to the general opinions, our meta-analysis showed comorbidities such as diabetes, hypertension, cardiopulmonary disorders, chronic kidney disease (CKD), age &gt;60, the duration of LT to the diagnosis of COVID-19, primary disease for LT, and obesity were not significantly associated with the severity and mortality in LT recipients with COVID-19 under an immunosuppressive therapy. However, our pooled analysis found that LT recipients with COVID-19 and without comorbidities have a less severe disease and low mortality rate compared to those with both COVID-19 and comorbidities.Conclusions: In conclusion, LT recipients with COVID-19 undergoing immunosuppressive therapies are not significantly associated with the severity and mortality. Therefore, taking the risk of organ rejection into a key consideration, a complete withdrawal of the IS may not be wise. However, mycophenolate mofetil (MMF) might be discontinued or replaced from an immunosuppressive regimen with the CNIs- or mTORis-based immunosuppressive therapy in some selected LT recipients with COVID-19, depending upon the severity of the disease.

scholarly journals Correlation between the Amount of Anti-D Antibodies and IgG Subclasses with Severity of Haemolytic Disease of Foetus and Newborn

2015 ◽  
Vol 3 (2) ◽  
pp. 293-297 ◽  
Author(s):  
Emilija Velkova
Keyword(s):  
Prospective Studies ◽  
Predictive Value ◽  
Research Study ◽  
Severe Disease ◽  
Foetal Death ◽  
Hemolytic Disease ◽  
Haemolytic Disease ◽  
A Value ◽  
Weak Intensity ◽  
Study Results

AIM: The aim of this study was to investigate the influence of subclasses to IgG anti-D on the intensity of hemolytic disease of fetus and newborn (HDFN) at 45 fetuses/newborns with symptoms of mild and severe HDFN in Republic of Macedonia.MATERIAL AND METHODS: In retrospective and prospective studies, in a period of 10 years, from 2004 to 2014, there have been immunohemathology tests performed on 22 009 samples on serums of pregnant women.RESULTS: At 37.78% of the total number of tested patients, IgG1 and IgG3 was the reason for severe HDFN. At 17.77% of the total number of tested patients, which had only IgG1detected, was the reason for serious intensity of HDFN. The correlation of the titer to anti-D antibodies in the mother’s serum and the intensity of HDFN were researched in 48 newborns. The titers between 1:8 and 1:32 resulted in 3 cases of HDFN with symptoms of severe disease and in 4 cases there were no signs of HDFN. At 12 women that had a titre between 1:32 and 1:512, five of the newborns developed severe HDFN, and seven had symptoms of mild and weak intensity form. In 3 cases the titer was higher than 512, and out of them one newborn had weak symptoms of HDFN, one developed severe HDFN and one ended with foetal death. Only in one case the titer reached a value higher than 1000, and it ended with a fetal death.CONCLUSIONS: The titers of the pregnant women serum those are lower than 32 and those higher than 1000 can well predict HDFN. The titers of anti-D antibodies between 64 and 512 have no exact predictive value. IgG1 and IgG3 subclasses of anti-D have no predictive value by themselves, and cannot foresee the outcome of HDFN. The research study results suggest that IgG1 and IgG3 should be included in a multi – parameter protocol for evaluation of the HDFN intensity. They can give a real assessment of the expected HDFN intensity in combination with the titer hight and the significance of the antibodies.

scholarly journals From Mouse to Man and Back: Closing the Correlation Gap between Imaging and Histopathology for Lung Diseases

Diagnostics ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 636 ◽  
Author(s):  
Birger Tielemans ◽  
Kaat Dekoster ◽  
Stijn E. Verleden ◽  
Stefan Sawall ◽  
Bartosz Leszczyński ◽  
...  
Keyword(s):  
Lung Disease ◽  
Disease Progression ◽  
Lung Diseases ◽  
Imaging Techniques ◽  
Treatment Options ◽  
Space Technology ◽  
Study Results ◽  
Life Threatening ◽  
End Stage

Lung diseases such as fibrosis, asthma, cystic fibrosis, infection and cancer are life-threatening conditions that slowly deteriorate quality of life and for which our diagnostic power is high, but our knowledge on etiology and/or effective treatment options still contains important gaps. In the context of day-to-day practice, clinical and preclinical studies, clinicians and basic researchers team up and continuously strive to increase insights into lung disease progression, diagnostic and treatment options. To unravel disease processes and to test novel therapeutic approaches, investigators typically rely on end-stage procedures such as serum analysis, cyto-/chemokine profiles and selective tissue histology from animal models. These techniques are useful but provide only a snapshot of disease processes that are essentially dynamic in time and space. Technology allowing evaluation of live animals repeatedly is indispensable to gain a better insight into the dynamics of lung disease progression and treatment effects. Computed tomography (CT) is a clinical diagnostic imaging technique that can have enormous benefits in a research context too. Yet, the implementation of imaging techniques in laboratories lags behind. In this review we want to showcase the integrated approaches and novel developments in imaging, lung functional testing and pathological techniques that are used to assess, diagnose, quantify and treat lung disease and that may be employed in research on patients and animals. Imaging approaches result in often novel anatomical and functional biomarkers, resulting in many advantages, such as better insight in disease progression and a reduction in the numbers of animals necessary. We here showcase integrated assessment of lung disease with imaging and histopathological technologies, applied to the example of lung fibrosis. Better integration of clinical and preclinical imaging technologies with pathology will ultimately result in improved clinical translation of (therapy) study results.

P070 TRENDS AND CHARACTERISTICS OF CLINICAL TRIALS PARTICIPATION IN THE IBD PARTNERS COHORT

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S11-S12
Author(s):  
Cole Johnson ◽  
Edward Barnes ◽  
Xian Zhang ◽  
Millie Long
Keyword(s):  
Clinical Trials ◽  
Controlled Trial ◽  
Severe Disease ◽  
Drug Approval ◽  
Cross Sectional Study ◽  
Participation Rates ◽  
Cross Sectional ◽  
Mild Disease ◽  
Randomized Controlled ◽  
Study Results

Abstract Background and Aims There are currently several recruitment challenges in randomized controlled trials (RCT) for inflammatory bowel disease (IBD) which prolong the drug approval process and affect the generalizability of study results. The purpose of this study is to characterize individuals who participate in IBD RCTs and identify factors which could influence future recruitment strategies. Methods We performed a cross-sectional study within the IBD Partners cohort comparing patients with current or prior participation in an interventional randomized controlled trial (RCT) of a medical therapy for IBD to those without any RCT participation. Bivariate statistics were used to compare RCT participation by IBD subtype and by other demographic and disease characteristics, and predictive modeling was used to identify factors predictive of RCT participation. We calculated the percent of the cohort that participated an in RCT during each calendar year from 2011–2018 and Clinicaltrials.gov was accessed to determine the number of active RCTs for IBD therapies per year during that same period. Results A total of 14,747 patients with IBD were included in the analysis and 1,116 (7.6%) reported RCT participation at any time. Demographic factors predictive of RCT participation (Table 1) included following at an academic institution (OR=1.8; 95%CI: 1.51–2.04) and age 36–75 (OR=1.6; 95%CI: 1.43–1.87). Patients with Crohn’s disease (CD) were more likely to participate than those with ulcerative colitis (UC) (OR=1.5; 95%CI: 1.35–1.77). Patients with more severe disease were more likely to participate, including those with prior IBD-related hospitalization (OR=2.6; 95%CI: 2.19–2.99), IBD-related surgery (OR=2.5; 95%CI: 2.24–2.87), biologic exposure (OR=3.2; 95%CI: 2.76–3.65), and “Poor” or worse quality of life (OR=1.7; 95%CI: 1.45–1.93). Steroid-free remission was associated with lower likelihood of RCT participation (OR=0.6; 95%CI: 0.53–0.70). While the number of active RCTs for IBD more than doubled between 2011 and 2018, RCT participation rates during that same time period decreased from 1.1% to 0.7% of the cohort (Figure 1). Conclusions RCT participation rates declined within this cohort between 2011–2018. Groups underrepresented in RCTs for IBD included younger patients, patients followed in community settings, and patients with more mild disease. The non-RCT group had mean sCDAI and SCCAI scores that did not meet remission thresholds, demonstrating populations in need of alternate therapies for whom clinical trials could be an option. Given anti-TNF exposure rates in this national cohort, studies should focus on anti-TNF failure populations. Investigators should make every effort to offer RCTs to all patients and network with community providers to increase awareness of RCTs.

scholarly journals Chronic anticoagulation is not associated with a reduced risk of acute kidney injury in hospitalised Covid-19 patients

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Kathrine Parker ◽  
Patrick Hamilton ◽  
Prasanna Hanumapura ◽  
Laveena Castelino ◽  
Michelle Murphy ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Anticoagulant Therapy ◽  
Severe Disease ◽  
Anticoagulation Therapy ◽  
Kidney Injury ◽  
World Health Organisation ◽  
World Health ◽  
Global Pandemic ◽  
Randomised Controlled ◽  
End Stage

Abstract Background Coronavirus-19 (COVID-19) has been declared a global pandemic by the World Health Organisation. Severe disease typically presents with respiratory failure but Acute Kidney Injury (AKI) and a hypercoagulable state can also occur. Early reports suggest that thrombosis may be linked with AKI. We studied the development of AKI and outcomes of patients with COVID-19 taking chronic anticoagulation therapy. Methods Electronic records were reviewed for all adult patients admitted to Manchester University Foundation Trust Hospitals between March 10 and April 302,020 with a diagnosis of COVID-19. Patients with end-stage kidney disease were excluded. AKI was classified as per KDIGO criteria. Results Of the 1032 patients with COVID-19 studied,164 (15.9%) were taking anticoagulant therapy prior to admission. There were similar rates of AKI between those on anticoagulants and those not anticoagulated (23.8% versus 19.7%) with no difference in the severity of AKI or requirement of renal replacement therapy between groups (1.2% versus 3.5%). Risk factors for AKI included hypertension, pre-existing renal disease and male sex. There was a higher mortality in those taking anticoagulant therapy (40.2% versus 30%). Patients taking anticoagulants were less likely to be admitted to the Intensive Care Unit (8.5% versus 17.4%) and to receive mechanical ventilation (42.9% versus 78.1%). Conclusion Patients on chronic anticoagulant therapy did not have a reduced incidence or severity of AKI suggesting that AKI is unlikely to be thrombotic in nature. Therapeutic anticoagulation is currently still under investigation in randomised controlled studies to determine whether it has a potential role in COVID-19 treatment.

Evaluation of Hepatobiliary Parameters During Eltrombopag Treatment in Patients with Chronic Immune Thrombocytopenic Purpura.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2410-2410 ◽  
Author(s):  
Willis C. Maddrey ◽  
Gregory Cheng ◽  
Abderrahim Khelif ◽  
Susan L Wroblewski ◽  
Andres Brainsky
Keyword(s):  
Liver Function ◽  
Immune Thrombocytopenic Purpura ◽  
Total Bilirubin ◽  
Clinical Symptoms ◽  
Draft Guidance ◽  
Thrombocytopenic Purpura ◽  
Screening Criteria ◽  
Chronic Immune Thrombocytopenic Purpura ◽  
Indirect Bilirubin ◽  
Hy’S Law

Abstract Abstract 2410 Poster Board II-388 BACKGROUND: Eltrombopag (PROMACTA®; GlaxoSmithKline, Collegeville, PA, USA) is an oral, small molecule, thrombopoietin receptor agonist that is approved in the US for the treatment of chronic immune thrombocytopenic purpura (ITP) and is being evaluated for the treatment of thrombocytopenia of various etiologies (eg, chronic liver disease, hepatitis C, MDS, chemotherapy). The prevalence of hepatobiliary laboratory abnormalities (HBLAs) in the overall population of chronic ITP patients, specifically ALT >3× ULN (4.6%), has been shown to be relatively high compared with other disease populations (Bennett Haematologica 2009). OBJECTIVE: To evaluate the effects of eltrombopag on the liver by analyzing HBLAs across the ITP clinical program. METHODS: Data were collected and analyzed from patients in 3 randomized, placebo-controlled (TRA100773A, TRA100773B, RAISE) and 2 open-label (REPEAT, EXTEND) eltrombopag studies. The analysis followed an FDA draft guidance on Drug-Induced Liver Injury (DILI), taking into consideration ALT or AST ≥3× ULN, total bilirubin or alkaline phosphatase (AP) >1.5× ULN, and potential combinations of these HBLAs. RESULTS: In the 3 placebo-controlled studies, 7% (9/128) of placebo patients and 11% (33/299) of eltrombopag patients met at least 1 of the DILI screening criteria (Table 1). In these studies, a similar incidence of abnormalities was observed in both treatment groups with the exception of ALT ≥3× ULN (placebo 2%; eltrombopag 5%). Total bilirubin elevations were observed in 3% and 4% of patients in the placebo and eltrombopag groups, respectively. 3 patients (2%) on placebo and 4 patients (2%) on eltrombopag were withdrawn due to elevations of ALT and/or total bilirubin. In REPEAT, 5% (3/66) of patients met at least 1 of the DILI screening criteria. Results in EXTEND were similar with 24 patients (8%) meeting at least 1 of the DILI screening criteria and 5 patients (2%) being withdrawn due to an HBLA. 18 EXTEND patients met at least 1 of the DILI screening criteria in a previous eltrombopag study. Of these, 7 patients (39%) met at least 1 of the DILI screening criteria during EXTEND; 5/7 experienced the same HBLAs as in the previous study. The recurrent HBLAs were generally of a lesser magnitude than the initial ones. In studies in which fractionation was required, 17 of the 18 patients with total bilirubin >1.5× ULN had hyperbilirubinemia due to indirect bilirubin. Bilirubin was not fractionated in 1 patient. Of the 60 eltrombopag-treated patients with HBLAs across the program, 25 patients (42%) had their elevations resolve despite continued eltrombopag treatment. Across the program, 5 patients had ALT >3× ULN and bilirubin >1.5× ULN (Table 1). Of these 5 patients, 3 provisionally met Hy's Law criteria (ALT 3× ULN and bilirubin >2× ULN). Ultimately, however, none of these patients met Hy's Law criteria as 1 patient had an increase in indirect bilirubin and 2 patients had confounding factors: 1 with acute cholangitis and 1 with septicemia and right-sided congestive heart failure. None of the patients experiencing HBLAs was reported to present with clinical symptoms indicative of liver function impairment. CONCLUSION: Eltrombopag treatment can lead to an elevation of ALT or indirect bilirubin. In clinical trials, these elevations have been typically mild, reversible and not accompanied by clinical symptoms indicative of impaired liver function. Disclosures: Maddrey: GlaxoSmithKline: Consultancy. Cheng:GlaxoSmithKline: Research Funding. Wroblewski:GlaxoSmithKline: Employment. Brainsky:GlaxoSmithKline: Employment.

Amrubicin (AMR) and cardiotoxicity in second-line treatment of small cell lung cancer (SCLC): A pooled analysis of left ventricular ejection fraction (LVEF) in two phase II trials

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19019-e19019
Author(s):  
D. R. Spigel ◽  
C. Shah ◽  
P. Lorigan ◽  
R. McNally ◽  
M. Renschler ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Pooled Analysis ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Line Treatment ◽  
Second Line ◽  
Phase Ii Trials ◽  
Two Phase ◽  
Ventricular Ejection Fraction ◽  
Study Results

e19019 Background: Amrubicin (AMR) is a third-generation synthetic anthracycline and a potent topoisomerase II inhibitor approved in Japan for the treatment of lung cancer. In Japanese pre and postmarking studies, AMR treatment was not associated with cardiotoxicity. The purpose of this analysis was to determine if AMR treatment of Western patients (pts) is associated with anthracycline-induced cardiomyopathy. Methods: To evaluate risk of cardiomyopathy, LVEF was measured by echocardiogram or by multiple gated acquisition (MUGA) scan and pooled from pts enrolled in 2 trials of IV AMR, 40 mg/m2/day x 3 days q 21 days for second-line treatment of sensitive or refractory SCLC. Pts with measurable disease, ECOG PS 0–2, LVEF ≥50%, and prior platinum-based treatment were assessed at baseline (BL), cycles 3, 6, then every 2 cycles, and end of treatment. Pts were to be assessed by the same method (ECHO or MUGA) throughout the study. Pts with a persistent ≥20% decrease in LVEF during treatment were to be removed from the study. Results: 112 patients were treated (sensitive n=43, median 6 cycles; refractory, n=69, median 5 cycles) and had at least 1 LVEF assessment. Median age was 63 years and median BL LVEF was 60%. Changes in LVEF from baseline were minimal ( Table ) and similar across cumulative dosing groups including 15 pts who received a cumulative dose of >1,000 mg/m2 AMR. Two refractory pts (1.8%) experienced drops in LVEF >20%. One had BL LVEF of 85%, then 60% at cycle 3, and 70% subsequently with ongoing therapy. The second, with a history of cardiomegaly, had LVEF of 55% at BL, cycle 3, and 5 by ECHO, and 29% at the time of progression after cycle 9 (cumulative AMR dose 840 mg/m2) by MUGA. The patient died due to progressive disease with no evidence of CHF. Conclusions: In this pooled analysis of SCLC pts, LVEF remained stable even in pts with cumulative AMR dosing >1,000 mg/m2. AMR for second-line treatment of SCLC does not appear to cause anthracycline-related cardiomyopathy. [Table: see text] [Table: see text]

Impact in delay of start of chemotherapy and surgery on pCR and survival in breast cancer: A pooled analysis of individual patient data from six prospectively randomized neoadjuvant trials.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 571-571 ◽  
Author(s):  
Sibylle Loibl ◽  
Gustavo Werutsky ◽  
Valentina Nekljudova ◽  
Sabine Seiler ◽  
Jens Uwe Blohmer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Pooled Analysis ◽  
Multivariable Logistic Regression Analysis ◽  
Time Interval ◽  
Cox Regression Analysis ◽  
Study Results ◽  
Survival Endpoints

571 Background: Time interval from diagnostic biopsy to neoadjuvant chemotherapy (NACT) start (TBC) and from last chemotherapy application to surgery (TCS) are influenced by many factors. It is unclear whether a delay of systemic therapy or surgery impacts patients (pts) outcome. Methods: 9127 pts with early BC from 6 German neoadjuvant trials receiving an anthracycline-taxane based NACT were included. pCR (ypT0/is ypN0), disease free survival (DFS) and overall survival (OS) were compared according to TBC and TCS length (cut-off of ≤4 vs >4weeks (w)), overall and in subgroups (BC subtypes [luminal, HER2+, triple-negative breast cancer (TNBC)] and pCR [yes vs no] for survival endpoints) adjusted by study. Results: Data on TBC were available for 8072 pts, on TCS for 6420, on follow-up (FU) for 7889. Median age was 49 yrs, 25.6% had cT3-4, 48.6% N+, 44.1% G3, 46.0% luminal, 26.4% TNBC, 27.6% HER2+ tumors. Median (m) FU-time was 65 months [0-201]. mTBC was 23 days [0-228] (67.5% ≤4w vs 32.5% >4w), mTCS was 28d [0-204] (53.7% ≤4w vs 46.3% >4w), with inter-study variability for mTBC ranging from 14 to 32d and for mTCS ranging from 24 to 29d from the oldest to the most recently conducted study. TBC did not influence the pCR rate, neither in all patients nor in subgroups. At multivariable logistic regression analysis TBC length did not independently predict pCR. TBC did not influence DFS or OS, neither in all patients nor in subgroups. TCS<4w was associated with a trend towards a better DFS in all patients (HR=1.11 95%CI (0.99-1.24), p=0.08) and in pts not achieving pCR (HR=1.12, 95%CI (0.99-1.26), p=0.08). No difference was observed within BC subtypes. OS was not impacted by TCS length. At multivariable Cox regression analysis TBC or TCS≤4 vs >4w did not independently influence DFS or OS. Conclusions: A delay in starting NACT does not impact the pCR rate, DFS or OS and results are independent of the subgroup. However, early surgery after NACT in pts without pCR seems to influence outcome. Our analysis is explorative, but indicates for the first time, that time interval of starting NACT and undergoing surgery might be uncritical. Further research is ongoing.

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