Association of cabozantinib residual concentration (Ctrough) and blood clearance (Cl/F) with toxicity (tox) and progressive disease (PD) in metastatic renal cell carcinoma (mRCC) patients (pts): Results from a monocentric pharmacokinetics (PK) study.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 292-292
Author(s):  
Luigi Cerbone ◽  
David Combarel ◽  
Stéphanie Foulon ◽  
Arthur Geraud ◽  
Carolina Alves ◽  
...  
Keyword(s):  
Blood Test ◽  
Progressive Disease ◽  
Drug Dose ◽  
Blood Clearance ◽  
Test Results ◽  
Blood Draw ◽  
Residual Concentration ◽  
Frequent Dose ◽  
Dose Modifications ◽  
Treatment Table

292 Background: Cabozantinib is a TKI with a substantial efficacy in mRCC. It is associated with a relevant tox leading frequent dose modifications (DM) or drug discontinuations (DD). While an exposure/safety relation has been demonstrated for this drug, an exposure/efficacy relation is still unknown. Cl/F is a measure of elimination of a drug from blood or plasma and lower Cl/F of cabozantinib has been previously associated with increased DM rate in mRCC. Methods: We performed a monocentric PK (INDS MR 5612140520) study in patients with mRCC. Blood draw for assessment of cabozantinib PK was performed at least 8 hours from the last drug dose. Ctrough was estimated with the following equation: Ctrough=Cmeas*0,5DI-24/t1/2. Ctrough and Cl/F were compared in patients with or without a relevant tox and in PD pts vs SD/PR pts. Relevant tox was defined either as G3-4 tox or G2 tox leading to DM or DD. Differences in Ctrough and CL were assessed between the groups with Mann Withney U test. Results: From 01.10.19 to 31.08.20 66 pts were included in this analysis. Twenty one relevant tox and 29 PD were observed. Ctrough was higher in pts experiencing relevant tox than in those who did not: 624,6 ng/ml (IQR 494-1030,2 ng/ml) vs 505,2 ng/ml (IQR 329,2-910,2), p0.012. Conversely Cl/F was lower in relevant tox vs not tox1,85 l/h (IQR 1,4-2,2 l/h) vs 2.27 l/h (IQR 1,7-3,2), p 0.024. In PD pts, Ctrough was lower than in SD/PR pts: 419ng/ml (IQR 317,2 -549,1 ng/ml) vs 554 ng/ml (IQR 416,9-795,6), p 0.0105, while Cl/F was higher in PD patients: 2,6 l/h (IQR 2,14-3,44 l/h) vs SD/PR patients 1.9 l/h (1,930 l/h;IQR 1,35-2,53 l/h); p= 0.011. Time from day cycle 1 to PK blood draw was significatively longer in non-tox pts and numerically longer in PD pts, which have the lowest Ctrough and the highest Cl/F. Conclusions: Cabozantinib toxicity is associated to a higher Ctrough and a lower Cl/F. Cabozantinib PD is associated to a lower Ctrough and a higher Cl/F. Cl/F should be assessed alongside with Ctrough in Cabozantinib PK blood test; Ctrough may decrease and conversely Cl/F may increase with time on treatment. [Table: see text]

Association of drug exposure with clinical response and toxicities in metastatic renal cell carcinoma patients (mRCC) receiving an alternative dosing (AD) regimen of sunitinib.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13582-e13582 ◽  
Author(s):  
Yi Ling Teo ◽  
Xiu Ping Chue ◽  
Noan-Minh Chau ◽  
Min-Han Tan ◽  
Ravindran Kanesvaran ◽  
...  
Keyword(s):  
Clinical Response ◽  
High Performance ◽  
Drug Exposure ◽  
Progressive Disease ◽  
Statistical Tests ◽  
Dosing Regimen ◽  
Frequent Dose ◽  
Common Grade ◽  
Hand Foot Syndrome ◽  
Dose Modifications

e13582 Background: An AD regimen of 37.5mg daily in repeated 4-weeks on, 2-weeks off cycle has been proposed to ameliorate frequent dose modifications due to toxicities as observed with the approved dosing regimen of sunitinib for mRCC. This study aims to determine the effect of drug exposure (sunitinib and active metabolite, SU12662) on clinical response and toxicities in patients receiving this AD regimen. Methods: All mRCC patients starting on sunitinib were invited to participate in this study. In week 4 of each cycle, toxicities were assessed and graded according to CTCAE and plasma AUCss was quantified using high-performance liquid chromatography. Clinical response was assessed after 2 treatment cycles; and was used with drug exposure and toxicities data for dose adjustments. Statistical tests such as Mann-Whitney U were used to compare the levels between groups. Results: 24 patients with a mean age of 58.8 ± 11.2 years were recruited. Majority were males (75%) and Chinese (87.5%). Among the 17 and 14 analyzable cases for cycle 1 and 2, median total AUCsswere 2.2 and 2.1 µg•h/ml respectively. Fourteen patients completed 2 treatment cycles; 7 (50%) partial response, 4 (28.6%)stable disease and 3 (21.4%) progressive disease. A dose increment to 50mg daily was performed for a patient with disease progression. Common grade 2 and above toxicities were hypertension, hand foot syndrome (HFS) and mucositis. Higher drug exposures were observed among patients who achieved clinical responseand among those who experienced at least grade 2 toxicities. Conclusions: Drug exposure could likely be associated with clinical response and toxicities in this AD regimen. [Table: see text]

Association between clinical response and toxicities with drug exposure in an alternative dosing regimen of sunitinib.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 439-439
Author(s):  
Ravindran Kanesvaran ◽  
Yi Ling Teo ◽  
Xiu Ping Chue ◽  
Noan-Minh Chau ◽  
Min-Han Tan ◽  
...  
Keyword(s):  
Clinical Response ◽  
High Performance ◽  
Drug Exposure ◽  
Progressive Disease ◽  
Dosing Regimen ◽  
Frequent Dose ◽  
Common Grade ◽  
Hand Foot Syndrome ◽  
Steady State Levels ◽  
Dose Modifications

439 Background: An alternative dosing (AD) regimen of 37.5mg daily in repeated 4-weeks on, 2-weeks off cycle has been proposed to ameliorate frequent dose modifications due to toxicities as observed with the approved dosing regimen of sunitinib for metastatic renal cell carcinoma (mRCC). This study aims to determine the effect of drug exposure (sunitinib and active metabolite, SU12662) on clinical response and toxicities in patients receiving this AD regimen. Methods: All mRCC patients initiating AD sunitinib were invited to participate in this study. In week 4 of each cycle, toxicities were assessed and plasma steady-state levels (Cmax) were quantified using high-performance liquid chromatography. Clinical response was assessed after 2 treatment cycles; and was used with drug exposure and toxicities data for dose adjustments. Results: 36 patients with a mean age of 59.1 ± 10.1 years were recruited. Majority were males (81%) and Chinese (86%). Among the 24 and 16 analyzable cases for cycle 1 and 2, median total Cmax were 0.088 and 0.094 µg/ml respectively. Sixteen patients completed 2 treatment cycles; 7 (44%) partial response, 5 (31%) stable disease and 4 (25%) progressive disease. A dose increment to 50mg daily was performed for a patient with disease progression. Common grade 2 and above toxicities were hypertension, hand foot syndrome (HFS) and mucositis. Higher drug exposures were observed among patients who achieved clinical response and among those who experienced at least grade 2 toxicities. Conclusions: Drug exposure could likely be associated with clinical response and toxicities in this AD regimen. [Table: see text]

scholarly journals Implementation of pharmacogenomic testing in oncology care (PhOCus): study protocol of a pragmatic, randomized clinical trial

2020 ◽  
Vol 12 ◽  
pp. 175883592097411
Author(s):  
Natalie Reizine ◽  
Everett E. Vokes ◽  
Ping Liu ◽  
Tien M. Truong ◽  
Rita Nanda ◽  
...  
Keyword(s):  
Clinical Laboratory ◽  
Drug Effects ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Clinical Decision ◽  
Drug Dose ◽  
Patient Specific ◽  
Drug Dosing ◽  
Patient Reported ◽  
Dose Modifications

Background: Many cancer patients who receive chemotherapy experience adverse drug effects. Pharmacogenomics (PGx) has promise to personalize chemotherapy drug dosing to maximize efficacy and safety. Fluoropyrimidines and irinotecan have well-known germline PGx associations. At our institution, we have delivered PGx clinical decision support (CDS) based on preemptively obtained genotyping results for a large number of non-oncology medications since 2012, but have not previously evaluated the utility of this strategy for patients initiating anti-cancer regimens. We hypothesize that providing oncologists with preemptive germline PGx information along with CDS will enable individualized dosing decisions and result in improved patient outcomes. Methods: Patients with oncologic malignancies for whom fluoropyrimidine and/or irinotecan-inclusive therapy is being planned will be enrolled and randomly assigned to PGx and control arms. Patients will be genotyped in a clinical laboratory across panels that include actionable variants in UGT1A1 and DPYD. For PGx arm patients, treating providers will be given access to the patient-specific PGx results with CDS prior to treatment initiation. In the control arm, genotyping will be deferred, and dosing will occur as per usual care. Co-primary endpoints are dose intensity deviation rate (the proportion of patients receiving dose modifications during the first treatment cycle), and grade ⩾3 treatment-related toxicities throughout the treatment course. Additional study endpoints will include cumulative drug dose intensity, progression-free survival, dosing of additional PGx supportive medications, and patient-reported quality of life and understanding of PGx. Discussion: Providing a platform of integrated germline PGx information may promote personalized chemotherapy dosing decisions and establish a new model of care to optimize oncology treatment planning.

scholarly journals Rapid point-of-care (POC) testing for Hepatitis C antibodies in a very high prevalence setting: persons injecting drugs in Tallinn, Estonia

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Anneli Uusküla ◽  
Ave Talu ◽  
Jürgen Rannap ◽  
David M. Barnes ◽  
Don Des Jarlais
Keyword(s):  
Hepatitis C ◽  
Point Of Care ◽  
Antibody Test ◽  
Hcv Rna ◽  
Test Results ◽  
Blood Draw ◽  
Persons Who Inject Drugs ◽  
Oral Swab ◽  
High Prevalence ◽  
Hcv Antibody

Abstract Background Between December 2018 and January of 2019, we evaluated the accuracy of the point-of-care Hepatitis C (HCV) antibody test (POC; OraQuick HCV) used at a community-based needle and syringe exchange program serving persons who inject drugs in Tallinn, Estonia. Methods We compared the results of screening for HCV antibodies by OraQuick (oral swab) and enzyme immunoassay (EIA; blood draw) and assessed test results implications in a high prevalence setting. Findings Of the 100 participants, 88 (88%) had reactive POC test results, and 93 were HCV antibody positive on EIA testing. Sensitivity, specificity and negative predictive value (NPV) for the POC assay with EIA as the relevant reference test were as follows: 94.6% (95% CI 90.0–99.2%), 100% and 58.3% (95% CI 30.4–86.2%). Of the 12 testing, HCV-negative with the POC only 7 (58.3%) were true negatives. Conclusions Oral swab rapid testing HCV screening in this nonclinical setting was sensitive and specific but had unacceptably low NPV. In high prevalence settings, POC tests with high sensitivity and that directly measure HCV RNA may be warranted.

scholarly journals The use of routine blood tests to assist the diagnosis of COVID-19 in symptomatic hospitalized patients

2021 ◽  
pp. 000456322199907
Author(s):  
IT Parsons ◽  
AT Parsons ◽  
E Balme ◽  
G Hazell ◽  
R Gifford ◽  
...  
Keyword(s):  
Cell Count ◽  
Retrospective Review ◽  
Blood Test ◽  
Patient Flow ◽  
White Cell Count ◽  
Area Under The Curve ◽  
White Cell ◽  
Test Results ◽  
Rt Pcr ◽  
Blood Tests

Introduction Specific patterns of blood test results are associated with COVID-19 infection. The aim of this study was to identify which blood tests could be used to assist in diagnosing COVID-19. Method A retrospective review was performed on consecutive patients referred to hospital with a clinical suspicion of COVID-19 over a period of four weeks. The patient’s clinical presentation and severe acute respiratory syndrome coronavirus 2 reverse-transcription polymerase chain reaction (SARS-CoV-2 RT-PCR) were recorded. The patients were divided by diagnosis into COVID (COVID-19 infection) or CONTROL (an alternate diagnosis). A retrospective review of consecutive patients over a further two-week period was used for the purposes of validation. Results Overall, 399 patients (53% COVID, 47% CONTROL) were analysed. White cell count, neutrophils and lymphocytes were significantly lower, while lactate dehydrogenase and ferritin were significantly higher, in the COVID group in comparison to CONTROL. Combining the white cell count, lymphocytes and ferritin results into a COVID Combined Blood Test (CCBT) had an area under the curve of 0.79. Using a threshold CCBT of –0.8 resulted in a sensitivity of 0.85 and a specificity of 0.63. Analysing this against a further retrospective review of 181 suspected COVID-19 patients, using the same CCBT threshold, resulted in a sensitivity of 0.73 and a specificity of 0.75. The sensitivity was comparable to the SARS-CoV-2 RT PCR. Discussion Mathematically combining the blood tests has the potential to assist clinical acumen allowing for rapid streaming and more accurate patient flow pending definitive diagnosis. This may be of particular use in low-resource settings.

Predicting abnormal laboratory blood test results in the intensive care unit using novel features based on information theory and historical conditional probability (Preprint)

2021 ◽  
Author(s):  
Camilo E. Valderrama ◽  
Daniel J. Niven ◽  
Henry T. Stelfox ◽  
Joon Lee
Keyword(s):  
Machine Learning ◽  
Intensive Care ◽  
Conditional Probability ◽  
Blood Test ◽  
Laboratory Tests ◽  
Conditional Entropy ◽  
Admission Diagnosis ◽  
Test Results ◽  
Abnormal Laboratory ◽  
Blood Tests

BACKGROUND Redundancy in laboratory blood tests is common in intensive care units (ICU), affecting patients' health and increasing healthcare expenses. Medical communities have made recommendations to order laboratory tests more judiciously. Wise selection can rely on modern data-driven approaches that have been shown to help identify redundant laboratory blood tests in ICUs. However, most of these works have been developed for highly selected clinical conditions such as gastrointestinal bleeding. Moreover, features based on conditional entropy and conditional probability distribution have not been used to inform the need for performing a new test. OBJECTIVE We aimed to address the limitations of previous works by adapting conditional entropy and conditional probability to extract features to predict abnormal laboratory blood test results. METHODS We used an ICU dataset collected across Alberta, Canada which included 55,689 ICU admissions from 48,672 patients with different diagnoses. We investigated conditional entropy and conditional probability-based features by comparing the performances of two machine learning approaches to predict normal and abnormal results for 18 blood laboratory tests. Approach 1 used patients' vitals, age, sex, admission diagnosis, and other laboratory blood test results as features. Approach 2 used the same features plus the new conditional entropy and conditional probability-based features. RESULTS Across the 18 blood laboratory tests, both Approach 1 and Approach 2 achieved a median F1-score, AUC, precision-recall AUC, and Gmean above 80%. We found that the inclusion of the new features statistically significantly improved the capacity to predict abnormal laboratory blood test results in between ten and fifteen laboratory blood tests depending on the machine learning model. CONCLUSIONS Our novel approach with promising prediction results can help reduce over-testing in ICUs, as well as risks for patients and healthcare systems. CLINICALTRIAL N/A

Diseases

1932 ◽  
Vol 5 (3-4) ◽  
pp. 73-130
Keyword(s):  
No Value ◽  
Blood Test ◽  
Agglutination Test ◽  
Test Results ◽  
Agglutination Titer ◽  
Poultry Farmers

Value of Agglutination-Test. - Der Wert der Agglutinations Methode bei der weissen Ruhr. Dr. Sachweh, München. Berliner Tierärztliche Wochenschrift, 1931, p. 845.A number of chickens were subjected, every three months, to the agglutination test. During this test it appeared that the agglutination titer varied considerably. All animals, of which a great number reacted positively at the beginning of the test, reacted negatively at the end thereof. This made it possible to comprehend the strongly varying results of the different tests. A group of 400 positive reacting hens gave healthy chicks. The wide advertising of the rapid blood test results in the poultry farmers making their own researches, and owing to the varying results obtained, it forces them to attach no value thereto.

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