scholarly journals Can individualized sunitinib dose and schedule changes optimize outcomes for kidney cancer patients?

2016 ◽  
Vol 10 (11-12) ◽  
pp. 252 ◽  
Author(s):  
Georg A. Bjarnason
Keyword(s):  
Cancer Patients ◽  
Kidney Cancer ◽  
Starting Dose ◽  
Recommended Starting Dose ◽  
Dose Reductions

The recommended starting dose and schedule for sunitinib is 50 mg daily for 28 days, followed by a 14-day break with significant dose reductions to 37.5 mg (75% of starting dose), and then 25 mg (50% of starting dose) on the same schedule (four/two schedule). There are several reasons why these dose and scheduling recommendations may not be optimal for most patients, as outlined below.

Impact of dose reductions on clinical outcomes among patients (pts) with metastatic pancreatic cancer (mPC) treated with liposomal irinotecan (nal-IRI) in oncology clinics in the United States.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 665-665 ◽  
Author(s):  
Paul Cockrum ◽  
Andy Surinach ◽  
George P. Kim ◽  
Daniel Mercer ◽  
Jim M. Koeller ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Real World ◽  
Treatment Initiation ◽  
The United States ◽  
Duration Of Treatment ◽  
Starting Dose ◽  
Liposomal Irinotecan ◽  
The Impact ◽  
Recommended Starting Dose ◽  
Dose Reductions

665 Background: The recommended starting dose for nal-IRI is 70mg/m2 (free base, equivalent to 80 mg/m2 salt-based dosing). This study evaluates the impact of nal-IRI dose reductions on clinical outcomes. Methods: Using the nationwide Flatiron Health electronic health record-derived database, de-identified data were extracted and analyzed for adult mPC pts treated with nal-IRI Jan 2014-Jan 2019 and who initiated treatment at approximately the recommended dose (RD), 70mg/m2 +/- 5mg. Initial dose was derived from structured medication records, prioritizing administrations. The cumulative dose (CD) of nal-IRI over the first six weeks of treatment, the presence of dose reductions (DR) – (a decrease ≥ 7mg/m2), overall survival (OS) from treatment initiation, and duration of treatment (DoT) were assessed. Results: 257 mPC pts treated with nal-IRI (median age: 68y, IQR: 61 - 73) were identified initiating therapy at approximately the RD. 26.5% (N = 68) of pts experienced a DR during treatment. Mean 6-week CD was 175.8 mg/m2 (SD: 77.9) among pts with no DR. For pts with DR, mean CD was 191.8 mg/m2 (53.2). Median DoT was 6.1 wks (IQR: 2.1 – 15.3). Pts that experienced a DR had a longer median DoT: 15.1 wks (7.1 – 23.0) vs 4.3. wks (2.1 – 12.1) for pts with no DR. Overall Median OS (mOS) was 4.2 months (95% CI: 3.7 – 5.4). mOS for DR pts was 7.2 mos (95% CI: 5.5 – 9.7) and 3.7 mos (3.0 – 4.1) for pts who did not experience a DR. Conclusions: This real-world analysis suggests that reducing the dose of subsequent administrations of nal-IRI during treatment is associated with pts remaining on therapy longer, experiencing a larger CD, and a with longer OS. Additional real-world prospective studies are necessary to characterize the impact of nal-IRI dosing on clinical outcomes.

Model-based analysis to support dose selection of pevonedistat (PEV) combined with azacitidine (AZA) in patients (pts) with higher-risk myelodysplastic syndromes (MDS)/chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7042-7042
Author(s):  
Xiaofei Zhou ◽  
Diane R. Mould ◽  
Dan Zhao ◽  
Mikkael A. Sekeres ◽  
Lionel Adès ◽  
...  
Keyword(s):  
Clinical Benefit ◽  
Phase 1 ◽  
Performance Status ◽  
Disease Type ◽  
International Prognostic Scoring System ◽  
Population Pharmacokinetic ◽  
Starting Dose ◽  
Grade 3 ◽  
The Impact ◽  
Dose Reductions

7042 Background: PEV+AZA has been studied in higher-risk MDS/CMML and AML, with encouraging efficacy and an acceptable safety profile without added myelosuppression. This pooled analysis was performed to evaluate the impact of PEV exposure on safety and efficacy. Methods: Data from three studies (NCT01814826, NCT02782468 and NCT02610777) were used in the PEV exposure–safety analyses, including ≥ grade 3 neutropenia (NEU3), febrile neutropenia (FN), ≥ grade 3 thrombocytopenia, ≥ grade 3 alanine aminotransferase elevation, ≥ grade 3 aspartate aminotransferase elevation and ≥ grade 3 treatment-emergent adverse event (TEAE3), in pts with higher-risk MDS/CMML and AML who received PEV+AZA. Data from NCT02610777 were used for exposure–efficacy analyses, including overall survival (OS), event-free survival (EFS), complete response (CR) and CR+partial response (PR), in pts with higher-risk MDS/CMML who received PEV+AZA. The exposure metrics for individual pts were derived from a previously developed population pharmacokinetic model with pooled data from eight phase 1/2 studies. PEV exposure–safety relationships for the toxicity endpoints, exposure–CR and exposure–CR+PR, were estimated by logistic regression. Age, sex, race, baseline Eastern Cooperate Oncology Group (ECOG) Performance Status score and disease type were evaluated as covariates. Cox proportional-hazards models were used to evaluate the PEV exposure–survival for higher-risk MDS/CMML, with age, sex, baseline ECOG PS score, Revised International Prognostic Scoring System score (IPSS-R) and disease type as potential covariates. Results: In total, 135 pts (median age, 74 years; male, 64%; Caucasian, 82%) and 41 pts (median age, 74 years; male, 76%; Caucasian, 90%; median IPSS-R, 5.5) were included in PEV exposure–safety and exposure–efficacy analyses, respectively. PEV exposure was significantly related to the incidence of NEU3 ( p = 0.003), FN ( p = 0.02) and TEAE3 ( p = 0.02), supporting PEV dose reductions for pts with treatment-related toxicities. Relationships between PEV exposures and CR, CR+PR, EFS or OS indicated consistent clinical benefit across ranges of PEV exposure following a starting dose of 20 mg/m2. Conclusions: The association between exposure and safety supports PEV dose reductions for pts with treatment-related toxicities. The exposure–efficacy analyses indicated consistent clinical benefit across ranges of PEV exposure following a starting dose of 20 mg/m2. These results support a favorable benefit–risk profile of the 20 mg/m2 PEV dose on days 1, 3 and 5 in combination with AZA 75 mg/m2 for 7 days in 28-day cycles. Clinical trial information: NCT01814826 , NCT02782468 , NCT02610777.

Beware of Non-Aspirin NSAIDs for Kidney Cancer Patients

2016 ◽  
Vol 38 (6) ◽  
pp. 21
Author(s):  
Ed Susman
Keyword(s):  
Cancer Patients ◽  
Kidney Cancer

Association Between Hospitals’ Risk-Adjusted Emergency Department Visits and Survival and Costs in Kidney Cancer Patients Undergoing Nephrectomy

2019 ◽  
Vol 17 (3) ◽  
pp. e650-e657
Author(s):  
Joel E. Segel ◽  
Eric W. Schaefer ◽  
Jay D. Raman ◽  
Christopher S. Hollenbeak
Keyword(s):  
Emergency Department ◽  
Cancer Patients ◽  
Kidney Cancer ◽  
Emergency Department Visits

scholarly journals Argatroban Dose Reductions for Suspected Heparin-Induced Thrombocytopenia Complicated by Child-Pugh Class C Liver Disease

2012 ◽  
Vol 46 (11) ◽  
pp. e30-e30 ◽  
Author(s):  
Peter M Yarbrough ◽  
Amir Varedi ◽  
Amanda Walker ◽  
Matthew T Rondina
Keyword(s):  
Liver Disease ◽  
Bleeding Complications ◽  
Severe Liver ◽  
Advanced Liver Disease ◽  
Heparin Induced Thrombocytopenia ◽  
Starting Dose ◽  
Severe Liver Disease ◽  
Pugh Class ◽  
Class C ◽  
Dose Reductions

OBJECTIVE: To report our experience of reduced-dose argatroban in a patient with suspected heparin-induced thrombocytopenia (HIT) and Child-Pugh class C liver disease and review the relevant literature to summarize current recommendations on argatroban use in patients with severe liver disease. CASE SUMMARY: A 58-year-old male with Child-Pugh class C liver disease (Model for End-Stage Liver Disease [MELD] score = 31, total bilirubin 4.5 mg/dL) and hemodialysis-dependent renal failure was hospitalized with acute deep vein thrombosis (DVT). Three days after heparin initiation for DVT, he developed thrombocytopenia. Given his heparin exposure (both for treatment of DVT and ongoing hemodialysis), HIT was suspected and all heparinoids were immediately discontinued. Argatroban was initiated for the treatment of HIT while laboratory testing for HIT antibodies and the serotonin release assay were completed. Because of the patient's advanced liver disease, the starting dose of argatroban was reduced to 0.2 μg/kg/min, with frequent monitoring of the activated partial thromboplastin time (aPTT) (goal 60–85 seconds). Despite this dose reduction, the aPTT was supratherapeutic. Following further dose reductions, a final argatroban maintenance dose of 0.05 μg/kg/min was necessary for the attainment of goal aPTTs. DISCUSSION: Reducing the starting dose of argatroban to 0.5 μg/kg/min is recommended in patients with liver disease. Nevertheless, this recommended dose is largely based on data from patients with more moderate liver disease (eg, Child-Pugh class A or B), and dosing in more advanced liver disease remains largely unexplored. Patients with more advanced liver disease may require additional dose reductions to avoid supratherapeutic concentrations of anticoagulation agents and to minimize bleeding risk. CONCLUSIONS: This report illustrates the importance of careful selection of argatroban dosing and appropriate aPTT monitoring in patients with severe liver disease. Excessive anticoagulation may precipitate major bleeding complications, placing patients with this complicated disease at undue risk.

scholarly journals The impact of metformin use on survival in kidney cancer patients with diabetes: a meta-analysis

2017 ◽  
Vol 49 (6) ◽  
pp. 975-981 ◽  
Author(s):  
Yang Li ◽  
Liyi Hu ◽  
Qinghong Xia ◽  
Yongqiang Yuan ◽  
Yonghua Mi
Keyword(s):  
Cancer Patients ◽  
Kidney Cancer ◽  
Meta Analysis ◽  
Patients With Diabetes ◽  
The Impact

Abstract 4687: Characterization of the cryoablation-induced immune response in kidney cancer patients

2017 ◽  
Author(s):  
Taigo Kato ◽  
Tomoyuki Iwasaki ◽  
Motohide Uemura ◽  
Akira Nagahara ◽  
Hiroki Higashihara ◽  
...  
Keyword(s):  
Immune Response ◽  
Cancer Patients ◽  
Kidney Cancer

scholarly journals The immunosuppressive phenotype of tumor-infiltrating neutrophils is associated with obesity in kidney cancer patients

2020 ◽  
Vol 9 (1) ◽  
pp. 1747731
Author(s):  
Camilla Margaroli ◽  
Maria A. Cardenas ◽  
Caroline S. Jansen ◽  
Adriana Moon Reyes ◽  
Fares Hosseinzadeh ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Kidney Cancer
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