scholarly journals Feasibility of Therapeutic Drug Monitoring of Sunitinib and its implications on response and toxicity in patients with metastatic renal cell cancer

2021 ◽  
Author(s):  
Khushboo Gandhi ◽  
Amit Joshi ◽  
Parsshava Mehta ◽  
Murari Gurjar ◽  
Pallavi Rane ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Renal Cell ◽  
Prospective Observational Study ◽  
Operating Characteristic ◽  
Cell Cancer ◽  
Therapeutic Drug ◽  
High Interindividual Variability ◽  
Grade 3 ◽  
Trough Levels

High interindividual variability in pharmacokinetics coupled with concentration-effect relationship make sunitinib an ideal candidate for therapeutic drug monitoring (TDM). The feasibility of TDM of sunitinib in patients with metastatic renal cell carcinoma (mRCC) was evaluated in this prospective observational study. Seventy patients with mRCC treated with sunitinib 50mg OD were enrolled. Total trough levels (TTL) of sunitinib and N-desethyl sunitinib were measured between days 10-14 of cycle 1. The discriminatory potential of TTL of sunitinib for the prediction of responders and occurrence of grade ≥3 toxicity was determined using receiver operating characteristic (ROC) curve. Threshold concentrations obtained from ROC analysis showed that TTL ≥60.75ng/mL was associated with higher response rates and TTL ≥82.3ng/mL was associated with higher incidence of grade ≥3 toxicity compared with lower exposures (31/34 versus 5/12, P=0.001 and 9/24 versus 4/36; P=0.024 respectively). More than 50% of patients in our cohort attained TTL outside the optimal range of 60.75-82.3 ng/mL demonstrating the feasibility of TDM.

Trough blood levels of sunitinib for Asian (Japanese) patients with metastatic renal cell carcinoma and therapeutic drug monitoring.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 508-508
Author(s):  
Yoshihide Kawasaki ◽  
Shinnya Takasaki ◽  
Akihiro Ito ◽  
Koji Mitsuzuka ◽  
Shinichi Yamashita ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Blood Concentration ◽  
Renal Cell ◽  
Japanese Patients ◽  
Therapeutic Drug ◽  
Blood Levels ◽  
Line Therapy ◽  
Trough Blood ◽  
Trough Levels

508 Background: The optimal blood concentration of total Sunitinib (SU) (SU + its active metabolite) is reportedly 50-100 ng/ml at trough levels according to the product literature. This is, however, based on models optimally calculated for Caucasians; hence, the desirable blood concentration for Asian patients, including Japanese, is unclear. We examined trough SU levels in Japanese patients with metastatic renal cell carcinomas (mRCC), to determine the preferred concentration of total SU and its doses. We also evaluated the efficacy and dependability of therapeutic drug monitoring (TDM) through the duration of therapy. Methods: Patients with mRCC scheduled for targeted therapy were prospectively recruited between November 2011 and August 2015. TDM of trough levels for patients treated with SU was performed on a regular basis. For this, blood samples were obtained immediately before administering SU on day 8 and day 15 after the initial administration day. Pre-therapeutic characteristics and post-therapeutic outcomes were evaluated. Relationships between pre-therapeutic characteristics, the dose of SU administered, adverse events (AEs) and total SU concentration at trough levels were determined. Results: Twenty of a total of 31 eligible patients were analyzed. Median patient age was 64 years (52-82), median BMI was 23.58 kg/m2 (17.7-32.78), and the average duration of SU therapy was 5 months (1-40). Seventeen patients were treated with SU as first-line therapy and 3 patients as second-line therapy after interferons. Patients with trough SU levels of over 80 ng/ml following the first course needed to discontinue SU due to AEs. All of the patients who obtained long-term stable disease (SD) or partial response (PR) without any AE > grade 2 were those with trough SU levels of 40-60 ng/ml. Conclusions: Our study suggests that trough total SU levels of 50-100 ng/ml are too high for Japanese people. And 40-80 ng/ml seems to be the preferable trough blood concentration of total SU after the first course of SU therapy in Japanese patients. TDM appears to be effective for the management of patients, to obtain optimal benefits of SU without AEs during therapy.

Therapeutic Drug Monitoring of Targeted Therapy in Metastatic Renal Cell Carcinoma

2018 ◽  
Vol 25 (6) ◽  
pp. 528-533
Author(s):  
Dehua Liao ◽  
Dangang Shangguan ◽  
Dunwu Yao ◽  
Qing Zhu ◽  
Lizhi Cao ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Therapeutic Drug Monitoring ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Drug Monitoring ◽  
Renal Cell ◽  
Therapeutic Drug

scholarly journals Feasibility of Extrapolating Randomly Taken Plasma Samples to Trough Levels for Therapeutic Drug Monitoring Purposes of Small Molecule Kinase Inhibitors

2021 ◽  
Vol 14 (2) ◽  
pp. 119
Author(s):  
Ruben A. G. van Eerden ◽  
Esther Oomen-de Hoop ◽  
Aad Noordam ◽  
Ron H. J. Mathijssen ◽  
Stijn L. W. Koolen
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Small Molecule ◽  
Trough Concentration ◽  
Drug Monitoring ◽  
Half Life ◽  
Kinase Inhibitors ◽  
Therapeutic Drug ◽  
Blood Samples ◽  
Elimination Half ◽  
Trough Levels

Small molecule kinase inhibitors (SMKIs) are widely used in oncology. Therapeutic drug monitoring (TDM) for SMKIs could reduce underexposure or overexposure. However, logistical issues such as timing of blood withdrawals hamper its implementation into clinical practice. Extrapolating a random concentration to a trough concentration using the elimination half-life could be a simple and easy way to overcome this problem. In our study plasma concentrations observed during 24 h blood sampling were used for extrapolation to trough levels. The objective was to demonstrate that extrapolation of randomly taken blood samples will lead to equivalent estimated trough samples compared to measured Cmin values. In total 2241 blood samples were analyzed. The estimated Ctrough levels of afatinib and sunitinib fulfilled the equivalence criteria if the samples were drawn after Tmax. The calculated Ctrough levels of erlotinib, imatinib and sorafenib met the equivalence criteria if they were taken, respectively, 12 h, 3 h and 10 h after drug intake. For regorafenib extrapolation was not feasible. In conclusion, extrapolation of randomly taken drug concentrations to a trough concentration using the mean elimination half-life is feasible for multiple SMKIs. Therefore, this simple method could positively contribute to the implementation of TDM in oncology.

scholarly journals Viral load Guided Immunosuppression after Lung Transplantation (VIGILung) – study protocol for a randomized controlled trial

2020 ◽  
Author(s):  
Jens Gottlieb ◽  
Alexander Reuss ◽  
Konstantin Mayer ◽  
Karin Weide ◽  
Carmen Schade-Brittinger ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Lung Transplantation ◽  
Drug Monitoring ◽  
Lung Transplant ◽  
Controlled Trial ◽  
Therapeutic Drug ◽  
Transplant Recipients ◽  
Randomized Controlled ◽  
Lung Transplant Recipients ◽  
Trough Levels

Abstract Background:Immunosuppression including high dose calcineurin-inhibitors (CNI) is essential after lung transplantation. Dosing is usually guided by therapeutic drug monitoring adjusted to target trough levels of CNIs to keep the balance between over-dose causing severe toxicity and increased risk of infections or under-dose with risk of graft-injury.Adaptation of CNI-based immunosuppression by monitoring of Torque-Teno-Virus (TTV) – a latent nonpathogenic DNA virus, measured in whole blood in addition to conventional therapeutic drug monitoring may reduce toxicity of immunosuppression with similar efficacy.Methods/Design:An open-label, randomized, controlled, parallel-group, multicenter trial in lung transplant recipients will be conducted to investigate the safety and efficacy of immunosuppression guided by TTV monitoring as add-on to conventional therapeutic drug monitoring. Adult lung transplant recipients 21 - 42 days after transplantation are eligible to participate. Patients (N = 144) will be randomized 1:1 to the experimental intervention (Arm 1: Immunosuppression guided by TTV monitoring in addition to conventional therapeutic drug monitoring of tacrolimus trough levels) and control intervention (Arm 2: conventional therapeutic drug monitoring). Outcomes will be assessed 12 months after randomization with the change in glomerular filtration rate as the primary endpoint. Secondary endpoints will be additional measurements on renal function, allograft function, incidence of acute rejections, incidence of chronic lung allograft dysfunction, graft loss and infections.Discussion:The results of this randomized controlled trial may reduce toxicity of immunosuppression after lung transplantation while maintaining efficacy of immunosuppression. Study results are transferable to all other solid organ transplantations.Trial registration: ClinicalTrials.gov, NCT04198506. Registered 12 December 2019, https://www.clinicaltrials.gov/show/NCT04198506

scholarly journals P050 Analysis of posaconazole therapeutic drug monitoring in paediatric haematology and oncology patients

2019 ◽  
Vol 104 (7) ◽  
pp. e2.55-e2 ◽  
Author(s):  
Natalie Donald ◽  
Ruth Edwards ◽  
Alison Thomson
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Fungal Infection ◽  
Broad Spectrum ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Paediatric Cancer ◽  
Oncology Patients ◽  
Paediatric Haematology ◽  
Paediatric Patients ◽  
Trough Levels

Posaconazole is a broad spectrum triazole antifungal with activity against a range of invasive fungal pathogens including Candida and Aspergillus species.1 Due to its range of activity it has been shown, by randomised controlled trials, to be superior to fluconazole and itraconazole for prevention of fungal infection in neutropenic patients,2 as well as being cost saving.1 Fungal prophylaxis with posaconazole has become the drug of choice within a paediatric cancer unit due to its broad spectrum of activity however there are significant differences in bioavailability of the suspension and tablet preparations and there is limited data relating to its use in the paediatric population.ObjectiveTo determine if the paediatric cancer unit is undertaking effective dosing and appropriate therapeutic drug monitoring (TDM) of posaconazole in paediatric haematology and oncology patients.MethodsA retrospective analysis of clinical data from 38 paediatric patients treated with posaconazole was undertaken. Patients received either 18–24-mg/kg/day posaconazole suspension in divided doses (maximum 800-mg/day,3 or 6–8-mg/kg/day posaconazole tablets (maximum 300-mg/day). Compliance with this guidance, initial and subsequent levels, efficacy and tolerability were analysed.SettingThe study was undertaken within the XXXX cancer unit; data for patients treated with posaconazole between January 2016 and August 2017 was reviewed.Key findingsThere was good compliance with the dosing advice for liquid and tablet posaconazole with 82% of patients dosed correctly. Due to this, the initial trough level of ≥0.7 mg/L was achieved in 82% of patients within 14 days of treatment initiation; there were no significant differences between formulations. Trough levels were monitored on a monthly basis for 71% of patients but dose adjustments were necessary in 34% of patients. Posaconazole had a good tolerability profile during the study with most side effects resolving on continuation of treatment however one patient had to discontinue the drug due to widespread rash. No patients developed a fungal infection whilst on posaconazole.ConclusionSafe and effective dosing and monitoring of posaconazole suspension and tablet formulations has been undertaken at the XXXX. Trough levels attained the desired target concentration of ≥0.7 mg/L in the majority of patients but dose adjustments were required with both formulations emphasising the need for regular TDM. Posaconazole was well tolerated and clinically effective in preventing fungal infection indicating its appropriateness in this patient group. From this review, a guideline for initiation and appropriate TDM of posaconazole can be developed.ReferencesDranitsaris G, Khoury H. Posaconazole versus fluconazole or itraconazole for prevention of invasive fungal infections in patients undergoing intensive cytotoxic therapy for acute myeloid leukemia or myelodysplasia: a cost effectiveness analysis. Supportive Care in Cancer. 2011; 19(11): 1807–1813.Cornely O, Maertens J, Winston D, et al. Posaconazole vs. Fluconazole or Itraconazole in Patients with Neutropenia. New England Journal of Medicine. 2007; 356(4): 348–359.Bernardo V, Cross S, Crews K, et al. Posaconazole Therapeutic Drug Monitoring in Paediatric Patients and Young Adults with Cancer. The Annals of Pharmacotherapy. 2013; 47: 976–983.

scholarly journals N22 Nurse led therapeutic drug monitoring (TDM) of Infliximab in IBD

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S667-S668
Author(s):  
S Gleeson ◽  
K Sugrue ◽  
M Buckley ◽  
J McCarthy
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Trough Concentration ◽  
Drug Monitoring ◽  
Response Assessment ◽  
Symptom Improvement ◽  
Therapeutic Drug ◽  
Serum Samples ◽  
Drug Concentrations ◽  
Biologic Response ◽  
Trough Levels

Abstract Background Therapeutic drug monitoring (TDM) is the clinical practice of measuring serum drug concentrations to guide clinical decision making. Achieving therapeutic drug concentrations has been associated with clinical, endoscopic and histological outcomes in IBD. The use of TDM offers a more personalised treatment approach and is associated with sustained clinical remission. Proactive TDM was introduced to the Mercy University Hospital in 2014 for all patients on biologics. Methods One hundred patients receiving biologic infusion (Infliximab) were evaluated post induction (week 12) for therapeutic drug trough concentration and for clinical response. Serum samples were taken from all IBD patients at week 12. Biologic response assessment forms were complete for all patients to assess symptom improvement. Results Thirty-five per cent of patients had sub therapeutic trough levels at week 12. They subsequently received 3 increased doses of 10mgs/kg and levels were rechecked. Of these 90% achieved therapeutic levels after the dose escalation. 65% of patients had therapeutic levels at week 12. There was a correlation between therapeutic trough levels and patient reported improvement of clinical symptoms in 85% of respondents. Conclusion TDM in our unit facilitates appropriate dose 100 patients receiving biologic infusion (Infliximab) were evaluated post induction (week 12) for therapeutic drug trough concentration and for clinical response. Serum samples were taken from all IBD patients at week 12. Biologic response assessment forms were complete for all patients to assess symptom improvement.

scholarly journals Vancomycin prophylaxis in paediatric patients following cardiac surgery: a retrospective evaluation of trough levels and associated variables

2020 ◽  
Vol 31 (5) ◽  
pp. 667-673
Author(s):  
Leonardo Vallesi ◽  
Tiziana Fragasso ◽  
Simona Benegni ◽  
Giulia Insom ◽  
Luca Di Chiara ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Therapeutic Drug ◽  
Clinical Predictors ◽  
Paediatric Patients ◽  
Number Of Patients ◽  
Vancomycin Trough ◽  
Optimal Target ◽  
Independent Association ◽  
Trough Levels

Abstract OBJECTIVES Therapeutic drug monitoring during vancomycin administration is recommended. However, little information is available in case of paediatric vancomycin prophylaxis. The aim of this study was to analyse vancomycin trough levels on postoperative day (POD) 2 and 3 after paediatric cardio-surgery to assess the clinical predictors and outcomes associated with vancomycin concentrations and to evaluate whether adjustments are effective to target optimal levels. METHODS A retrospective study was conducted in paediatric patients receiving vancomycin prophylaxis after elective cardio-surgery. Adjustments were made if levels between 20 and 30 (halving subsequent dose) or ˃30 mg/l (dose withheld) were found. RESULTS Vancomycin doses of the 100 examined children (3.7–6.4 years) were 12.8 (2.5), 9.4 (5.4) and 9.7 (4.5) mg/kg, on POD1, 2 and 3, respectively (P = 0.0001). The 200 vancomycin trough levels decreased from 16.9 (11.4) on POD2 to 14.6 (8.5) on POD3 (P = 0.003). Overall, 66 troughs were sub-target, 68 reached the optimal target and 66 were supra-target. On POD2 and 3, 32 and 27 dose adjustments were required, leading to a reduced number of patients with supra-target troughs. Neonates showed a higher number of supra-target levels with respect to non-neonatal patients on both POD2 (P = 0.003) and 3 (P = 0.0001). At multivariable regression analysis, vancomycin levels showed independent association with weight and creatinine levels on both POD2 and 3. Vancomycin levels correlated with ventilation days (P = 0.31, P = 0.039), but not with methicillin-resistant Staphylococcus aureus positivity (P = 0.69). CONCLUSIONS Vancomycin prophylaxis in paediatric cardio-surgery requires strict therapeutic drug monitoring and several dosage adjustments. Supra-target troughs are frequent and neonatal age, weight and creatinine levels significantly affect vancomycin concentrations.

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