Oral Presentations 6: TDM in Oncology
Tracks
Track 2
| Monday, September 22, 2025 |
| 4:00 PM - 5:00 PM |
| Grand Copthorne Waterfront Hotel - Waterfront Ballroom III |
Speaker
Mr Eugene Tan
College of Medicine and Public Health, Flinders Health and Medical Research Institute, Flinders University
Therapeutic Drug Monitoring of Everolimus in Cancer Patients: A Single-Centre Experience
Abstract
Purpose: Everolimus, a targeted therapy is used in various cancers and transplant medicine. While therapeutic drug monitoring (TDM) of everolimus is standard practice in transplant settings to optimise dosing and manage toxicity, its application in oncology is not mandated. This single-centre review investigates the potential benefits of TDM, a precision dosing method, in cancer patients prescribed everolimus.
Methods: Medical records from a public hospital in South Australia, were retrospectively reviewed for patients treated with everolimus for cancer indications between January 1, 2013, and December 31, 2023. Data on whole blood everolimus concentrations, cancer diagnoses, dosing regimens, survival outcomes, and demographics were collected and analysed.
Results: During the study period, 53 patients with a median age of 64 years (range:38 – 85) were treated with everolimus. Diagnoses included metastatic breast cancer (MBC, n=41), metastatic renal cancer (n=6), neuroendocrine tumours (n=4), and recurrent ovarian cancer (n=2). Among these, 14 patients (26%) underwent at least one everolimus blood level assessment. In the MBC cohort, the median overall survival was 20.5 months for patients with TDM-guided treatment (n=10) compared to 15.1 months for those without TDM (n=31), a difference that was not statistically significant (HR=0.87, 95% CI:0.42 – 1.79, p=0.70). Importantly, all MBC patients who underwent TDM-guided dose adjustments avoided treatment discontinuation due to adverse effects.
Conclusion: This study highlights the underutilisation of TDM in oncology and its potential to optimise everolimus dosing and minimise toxicity. Prospective studies are warranted to establish therapeutic ranges and confirm the clinical benefits of TDM in cancer care.
Methods: Medical records from a public hospital in South Australia, were retrospectively reviewed for patients treated with everolimus for cancer indications between January 1, 2013, and December 31, 2023. Data on whole blood everolimus concentrations, cancer diagnoses, dosing regimens, survival outcomes, and demographics were collected and analysed.
Results: During the study period, 53 patients with a median age of 64 years (range:38 – 85) were treated with everolimus. Diagnoses included metastatic breast cancer (MBC, n=41), metastatic renal cancer (n=6), neuroendocrine tumours (n=4), and recurrent ovarian cancer (n=2). Among these, 14 patients (26%) underwent at least one everolimus blood level assessment. In the MBC cohort, the median overall survival was 20.5 months for patients with TDM-guided treatment (n=10) compared to 15.1 months for those without TDM (n=31), a difference that was not statistically significant (HR=0.87, 95% CI:0.42 – 1.79, p=0.70). Importantly, all MBC patients who underwent TDM-guided dose adjustments avoided treatment discontinuation due to adverse effects.
Conclusion: This study highlights the underutilisation of TDM in oncology and its potential to optimise everolimus dosing and minimise toxicity. Prospective studies are warranted to establish therapeutic ranges and confirm the clinical benefits of TDM in cancer care.
Biography
Eugene is an early-career clinical pharmacist currently working at Flinders Medical Centre. With a strong foundation in clinical pharmacy, Eugene is dedicated to optimising patient care through evidence-based medication management. He professional interests lie in oncology, where he has gained valuable research experience exploring the effectiveness and safety of various cancer therapies.
Currently, Eugene is being mentored by Dr Kichenadasse with funding support from the Ryan Hodges Foundation to investigate precision dosing methods for anticancer medicines. His research focuses on optimising treatment strategies to enhance efficacy while minimising toxicity. Actively collaborating with oncologists, pharmacologists, and consumers, Eugene works to bridge the gap between clinical practice and research, ensuring that patient-centered approaches drive advancements in oncology therapeutics. Through this collaboration, he aims to develop evidence-based dosing strategies that improve treatment outcomes and enhance the safety of anticancer medications.
Dr Natansh Modi
University Of South Australia
Co-presenter
Biography
Dr. Natansh Deepak Modi is a Lecturer in Pharmacy at University of South Australia. His expertise spans clinical epidemiology, pharmacology and healthcare-focused artificial intelligence research, particularly exploring AI-driven disinformation and its societal impact. Passionate about pharmacy practice, Natansh is actively engaged in developing innovative pharmacy education methods and advocates for greater transparency in clinical research.
Mrs Min Zhang
Department Of Pharmacy, Chongqing University Cancer Hospital, Chongqing 400030, China
HDMTX: Risk Factors of Delayed Excretion and Related ADR in NHL Patients
Abstract
Background: High-dose methotrexate (HDMTX), a important treatment for non-Hodgkin lymphoma (NHL), is often complicated by delayed excretion and associated adverse reactions, significantly impacting patient safety.
Aims: This study aims to investigate the influencing factors for delayed excretion and its correlation with adverse reactions (ADR) in NHL patients receiving HDMTX chemotherapy, offering insights for the safe use of MTX.
Methods: From January 26, 2021 to August 18, 2024, the NHL patients who received HDMTX chemotherapy from Chongqing University Cancer Hospital were collected. Using univariate and multivariate logistic regression, the study investigated the factors affecting the delayed excretion of HDMTX and ADR of grade 2 or higher associated with delayed excretion.
Results: This study included 137 patients,comprising 437 courses of HDMTX. Delayed excretion of HDMTX occurred in 55 patients (40.1%), and 31 patients (56.4%) of patients with delayed excretion at 72-hour. Interestingly, the MTX concentrations of 5 patients dropped to the target range but then rose again to exceed the safe concentration. ADR associated with delayed excretion included white blood cell reduction, acute kidney injury, elevated uric acid, and infection. The number of HDMTX treatment courses (p=0.002) and white blood cell levels (p=0.032) were identified as independent risk factors for delayed excretion. Additionally, independent risk factors for delayed excretion with grade 2 or higher ADR included the MTHFR T allele (p=0.008) and weight ≤50 kg (p=0.029).
Conclusions: When using HDMTX, patients with the MTHFR T allele and weight ≤50 kg should be closely monitored for MTX levels and ADR.
Aims: This study aims to investigate the influencing factors for delayed excretion and its correlation with adverse reactions (ADR) in NHL patients receiving HDMTX chemotherapy, offering insights for the safe use of MTX.
Methods: From January 26, 2021 to August 18, 2024, the NHL patients who received HDMTX chemotherapy from Chongqing University Cancer Hospital were collected. Using univariate and multivariate logistic regression, the study investigated the factors affecting the delayed excretion of HDMTX and ADR of grade 2 or higher associated with delayed excretion.
Results: This study included 137 patients,comprising 437 courses of HDMTX. Delayed excretion of HDMTX occurred in 55 patients (40.1%), and 31 patients (56.4%) of patients with delayed excretion at 72-hour. Interestingly, the MTX concentrations of 5 patients dropped to the target range but then rose again to exceed the safe concentration. ADR associated with delayed excretion included white blood cell reduction, acute kidney injury, elevated uric acid, and infection. The number of HDMTX treatment courses (p=0.002) and white blood cell levels (p=0.032) were identified as independent risk factors for delayed excretion. Additionally, independent risk factors for delayed excretion with grade 2 or higher ADR included the MTHFR T allele (p=0.008) and weight ≤50 kg (p=0.029).
Conclusions: When using HDMTX, patients with the MTHFR T allele and weight ≤50 kg should be closely monitored for MTX levels and ADR.
Biography
Zhang Min, Master of Clinical Pharmacy. Engaged as a clinical pharmacist specializing in hematologic oncology in department of pharmacy, Chongqing University Cancer Hospital.
Prof Rongsheng Zhao
Director of Pharmacy Department
Peking University Third Hospital
Implementation of TDM Guideline-based Standardized Supportive Care Improves Safety of Methotrexate Treatment
Abstract
Background: High-dose methotrexate (HDMTX) is an essential component of treatment protocols in hematologic malignancies. However, common toxicities during HDMTX therapy still remain to be further managed. Herein, to promote individualized medication and supportive care of HDMTX, the Division of TDM of Chinese Pharmacological Society launched the TDM guideline of HDMTX therapy in November 2021.
Aims: To investigated the effect of implementing TDM guideline-based standardized supportive care on patient safety during HDMTX therapy.
Methods: A seven-year ambidirectional cohort study including a 5-year retrospective (367 Cycles) and 2-year prospective study (244 Cycles) was conducted between January 2017 and December 2023. The TDM guideline-based standardized supportive care was provided initially in January 2022 (Intervention group), and it was defined as empirical therapy before this (Empirical group). Adult patients with hematologic malignancies received HDMTX chemotherapy were included. Outcomes measured included adverse drug events (ADEs) (including liver function damage and myelosuppression), unreasonable co-combinations with proton pump inhibitors (PPIs) and delayed elimination.
Results: In intervention group, a significant decrease of myelosuppression (51.2% vs 60.8%, P=0.02) and liver function damage (18.4% vs 25.3%, P=0.046) was observed in comparison to empirical cohort. The incidence of unreasonable co-combinations with PPIs was also significantly reduced (37.3%. vs. 52.3%, P<0.001). Delayed elimination was observed in 11.1% of cycles in intervention cohort opposed to 13.4% in empirical group.
Conclusions: The implementation of TDM guideline-based standardized supportive care during HDMTX therapy is recommended to improve patient safety. More attention should be paid to TDM guidelines' implementation.
Key Words: Methotrexate, ADEs, TDM, guideline implementation
Aims: To investigated the effect of implementing TDM guideline-based standardized supportive care on patient safety during HDMTX therapy.
Methods: A seven-year ambidirectional cohort study including a 5-year retrospective (367 Cycles) and 2-year prospective study (244 Cycles) was conducted between January 2017 and December 2023. The TDM guideline-based standardized supportive care was provided initially in January 2022 (Intervention group), and it was defined as empirical therapy before this (Empirical group). Adult patients with hematologic malignancies received HDMTX chemotherapy were included. Outcomes measured included adverse drug events (ADEs) (including liver function damage and myelosuppression), unreasonable co-combinations with proton pump inhibitors (PPIs) and delayed elimination.
Results: In intervention group, a significant decrease of myelosuppression (51.2% vs 60.8%, P=0.02) and liver function damage (18.4% vs 25.3%, P=0.046) was observed in comparison to empirical cohort. The incidence of unreasonable co-combinations with PPIs was also significantly reduced (37.3%. vs. 52.3%, P<0.001). Delayed elimination was observed in 11.1% of cycles in intervention cohort opposed to 13.4% in empirical group.
Conclusions: The implementation of TDM guideline-based standardized supportive care during HDMTX therapy is recommended to improve patient safety. More attention should be paid to TDM guidelines' implementation.
Key Words: Methotrexate, ADEs, TDM, guideline implementation
Biography
Prof. Zhao is a Doctoral Supervisor at Peking University and Macau University of Science and Technology, an Honorary Professor at the University of Manchester (UK), and a Member of the ACCP Board of Regents.
As a leading expert in hospital pharmacy and clinical pharmacy, Prof. Zhao holds key positions in national and international organizations, including: Chinese Pharmacopoeia Commission (Member); Committee on Pharmacy Administration and Pharmacotherapy, National Health Commission of China (Member); Pharmaceutical Specialized Committee, Chinese Hospital Association (Chair); Committee on Patient Education and Science Popularization, Chinese Pharmacists Association (Chair); Hospital Pharmacy & Evidence-Based Pharmacy Committees, Chinese Pharmaceutical Association (Vice Chair); Therapeutic Drug Monitoring Research Committee, Chinese Pharmacological Society (Vice Chair).
He serves as Editor-in-Chief of AJHP (Chinese Edition) and Deputy Editor-in-Chief of multiple prestigious journals, including China Pharmacy, Evaluation and Analysis of Drug-Use in Hospitals of China, Chinese Journal of New Drugs, Clinical Medication Journal and China Pharmaceuticals.
Prof. Zhao's research focuses on precision medicine, therapeutic drug monitoring, and evidence-based pharmacy practice. He has led 38 research projects (including National Natural Science Foundation grants), published over 310 academic papers (3 ESI highly cited), and obtained 20 national invention patents. He has been honored with the Wu Jieping-Paul Janssen Award, China Pharmaceutical Association Science and Technology Award, and other distinguished accolades for his contributions to pharmaceutical sciences and clinical pharmacy.
Dr Niveditha K
Kasturba Medical College, Manipal, Manipal Academy Of Higher Education, Manipal
Pharmacogenomic influence on high dose methotrexate pharmacokinetics, outcomes, adverse effects in leukaemia
Abstract
Background: Acute lymphoblastic leukemia (ALL) is a common hematological cancer in the pediatric age group, accounting for 30%. Similarly, incidence among AYA population (Young adolescence and adults) has raised in recent decades. High dose Methotrexate (HDMTX), is one of the important chemotherapeutic agent administered in consolidation phase of Berlin-Frankfurt-Munster (BFM) protocol. Routine therapeutic drug monitoring of plasma HDMTX levels has been strongly recommended.
Aims: We aimed to determine the correlation of Influence of pharmacogenetics polymorphism of genes encoding MTX enzymes and transporters (SLCO1B1, MTHFR, SLC19A1) with plasma levels, clinical outcome and adverse effects of HDMTX.
Methods: We recruited 112 patients with ALL who received 4 cycles of HDMTX administration with interval of 15 days between the each cycle. The 2 ml blood samples were collected at following time points: 24 hours, 48 hours and 72 hours post HDMTX infusion in each cycle. The following parameters were assessed : genetic polymorphisms by Sanger sequencing, plasma methotrexate levels by LCMS/MS, clinical outcome by minimal residual disease (MRD) at end of consolidation and adverse events by Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Results: We observed a wide inter-individual variability in levels of methotrexate at 24 hours, 48 hours and 72 hours in all 4 cycles. The correlation of SNPs (SLCO1B1, SLC19A1) with plasma MTX at 48 and 72 hours of delayed elimination of HDMTX (P value : <0.05) was significant.
Conclusions: The pharmacogenomics and pharmacokinetics are vital for individualized therapy to optimize efficacy and minimize toxicity of high dose methotrexate.
Aims: We aimed to determine the correlation of Influence of pharmacogenetics polymorphism of genes encoding MTX enzymes and transporters (SLCO1B1, MTHFR, SLC19A1) with plasma levels, clinical outcome and adverse effects of HDMTX.
Methods: We recruited 112 patients with ALL who received 4 cycles of HDMTX administration with interval of 15 days between the each cycle. The 2 ml blood samples were collected at following time points: 24 hours, 48 hours and 72 hours post HDMTX infusion in each cycle. The following parameters were assessed : genetic polymorphisms by Sanger sequencing, plasma methotrexate levels by LCMS/MS, clinical outcome by minimal residual disease (MRD) at end of consolidation and adverse events by Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Results: We observed a wide inter-individual variability in levels of methotrexate at 24 hours, 48 hours and 72 hours in all 4 cycles. The correlation of SNPs (SLCO1B1, SLC19A1) with plasma MTX at 48 and 72 hours of delayed elimination of HDMTX (P value : <0.05) was significant.
Conclusions: The pharmacogenomics and pharmacokinetics are vital for individualized therapy to optimize efficacy and minimize toxicity of high dose methotrexate.
Biography
Completed the super speciality (DM, Clinical Pharmacology) from prestigious institute of India, PGIMER, Chandigarh. Journey of academician started just 15 days back in new place, Manipal institute.
Holding degrees from 2 prestigious institute of India (MBBS, MD and DNB , DM from JIPMER and PGIMER) gives immense pleasure to serve the community with greatest motivation.
Starting the TDM work in new place, as its the most interested area to build the knowledge and shorten the gaps between TDM team and prescriber.
Also very much interested in personalised medicine, MIPD, Pharmacometrics and machine learning. Diving into modelling and simulation along with population PK to dose optimisation were explored since past 10 years of academic career. Lastly wish to continue learning in the TDM field as its utmost important to contribute to patient service and research for future.
Assist Prof Khushboo Bisht
Assistant Professor
All India Institute Of Medical Sciences, Nagpur; All India Imstitute Of Medical Sciences, Rishikesh
Melatonin and Chrono-Modulation affect Gemcitabine Pharmacokinetics and CDA activity (MEGA-CLOCK)
Abstract
Background:
The timing of chemotherapy administration and adjunctive therapies like melatonin may influence drug metabolism, efficacy, and tolerability. This study evaluates the effects of chrono-modulated gemcitabine infusion and melatonin supplementation on gemcitabine pharmacokinetics and cytidine deaminase (CDA) activity in metastatic cancer patients.
Aims:
To assess the impact of chrono-modulated gemcitabine administration and melatonin supplementation on gemcitabine elimination kinetics, CDA activity, and chemotherapy-related adverse effects.
Methods:
This study included 14 metastatic cancer patients receiving gemcitabine (1000 mg/m² over 30 minutes) at either 09:00 or 15:00 hours. A subgroup received melatonin supplementation. Plasma gemcitabine concentrations and CDA activity were measured. Adverse effects were assessed using CTCAE 5.0. Ethical approval was obtained, and the study was registered with the Clinical Trials Registry of India (CTRI).
Results:
Chrono-modulated administration did not significantly impact gemcitabine elimination kinetics or CDA activity. However, evening administration was associated with a higher incidence of adverse effects. Melatonin supplementation did not significantly alter CDA activity but increased % extrapolated AUMC (10.29% vs. 4.71%, p = 0.011), indicating altered drug elimination dynamics.
Conclusions:
While chrono-modulation did not affect gemcitabine pharmacokinetics, evening administration correlated with increased adverse effects. Melatonin influenced gemcitabine disposition without significantly altering overall pharmacokinetics or CDA activity. Further research is required to determine the clinical implications of these findings.
Key Words: Chrono-modulation, gemcitabine, melatonin, cytidine deaminase, pharmacokinetics, chemotherapy
The timing of chemotherapy administration and adjunctive therapies like melatonin may influence drug metabolism, efficacy, and tolerability. This study evaluates the effects of chrono-modulated gemcitabine infusion and melatonin supplementation on gemcitabine pharmacokinetics and cytidine deaminase (CDA) activity in metastatic cancer patients.
Aims:
To assess the impact of chrono-modulated gemcitabine administration and melatonin supplementation on gemcitabine elimination kinetics, CDA activity, and chemotherapy-related adverse effects.
Methods:
This study included 14 metastatic cancer patients receiving gemcitabine (1000 mg/m² over 30 minutes) at either 09:00 or 15:00 hours. A subgroup received melatonin supplementation. Plasma gemcitabine concentrations and CDA activity were measured. Adverse effects were assessed using CTCAE 5.0. Ethical approval was obtained, and the study was registered with the Clinical Trials Registry of India (CTRI).
Results:
Chrono-modulated administration did not significantly impact gemcitabine elimination kinetics or CDA activity. However, evening administration was associated with a higher incidence of adverse effects. Melatonin supplementation did not significantly alter CDA activity but increased % extrapolated AUMC (10.29% vs. 4.71%, p = 0.011), indicating altered drug elimination dynamics.
Conclusions:
While chrono-modulation did not affect gemcitabine pharmacokinetics, evening administration correlated with increased adverse effects. Melatonin influenced gemcitabine disposition without significantly altering overall pharmacokinetics or CDA activity. Further research is required to determine the clinical implications of these findings.
Key Words: Chrono-modulation, gemcitabine, melatonin, cytidine deaminase, pharmacokinetics, chemotherapy
Biography
Dr Khushboo Bisht is an enthusiastic Clinical Pharmacologist from India, MD (Pharmacology) from AIIMS, Delhi and DM (Clinical Pharmacology) from AIIMS, Rishikesh. She has obtained membership of the British Pharmacological Society (UK) and South-Asian College, an affiliate of American College of Clinical Pharmacology. Dr Khushboo joined Amrita Institute of Medical Sciences, Faridabad since 2024. She is Assistant Professor, Department of Pharmacology, training undergraduates and postgraduates with her experience in the field of Clinical Pharmacology. Her areas of interest in research work are cardiovascular pharmacology, onco-therapeutics, geriatric pharmacology antimicrobial stewardship, patient safety and medical ethics. She excels in designing and conducting clinical trials. She is actively engaged in academic roles and clinical research with multiple publications in international peer-reviewed journals, book chapters and awards to her credit.
