Cancer Chemotherapy: The Case for Therapeutic Drug Monitoring

Knezevic, Claire E.; Clarke, William

doi:10.1097/ftd.0000000000000701

Cited by 60 publications

(49 citation statements)

References 145 publications

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“…Of 27 cytotoxic antineoplastic agents among reports, four had 25 or more publications identified (methotrexate, 5-fluorouracil, carboplatin, paclitaxel; Table 1 ). Though not universal, TDM is established practice for two of these agents, methotrexate and 5-fluorouracil, while for paclitaxel evidence is emerging and clinical application is at present not widespread ( 2 , 11 , 12 ). Although taxanes were discovered in the 1960s, paclitaxel, the first commercially available agent, obtained regulatory approval in 1992 due to challenges with synthesis and formulation ( 13 ).…”

Section: Discussionmentioning

confidence: 99%

“…Although TDM has been used to support dosing decisions for some antineoplastics since the 1970s ( 1 ), it is not universally applied. TDM guided dosing is accepted for specific antineoplastics in specific clinical contexts, including high-dose methotrexate, busulfan and thiopurines ( 2 ). However, dosing based on weight and/or body surface area (BSA) continues to be the dominant approach despite observation of wide interpatient variability in systemic drug concentrations ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic drug monitoring in oncology - What’s out there: A bibliometric evaluation on the topic

et al. 2022

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Pharmacological therapy is the mainstay of treatment for cancer patients. Despite wide interpatient variability in systemic drug concentrations for numerous antineoplastics, dosing based on body size remains the predominant approach. Therapeutic drug monitoring (TDM) is used for few antineoplastics in specific scenarios. We conducted a rapid bibliometric evaluation of TDM in oncology to capture a snapshot of research in this area over time and explore topics that reflect development in the field. Reports with the composite, indexed term ‘therapeutic drug monitoring’ in the title and abstract were extracted from MEDLINE (inception to August 2021). Reports related to applications in cancer were selected for inclusion and were tagged by study design, antineoplastic drugs and concepts related to TDM. We present a timeline from 1980 to the present indicating the year of first report of antineoplastic agents and key terms. The reports in our sample primarily reflected development and validation of analytical methods with few relating to clinical outcomes to support implementation. Our work emphasises evidence gaps that may contribute to poor uptake of TDM in oncology.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Therapeutic drug monitoring in oncology - What’s out there: A bibliometric evaluation on the topic

et al. 2022

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“…For a treatment to be successful, a sufficient amount of the drug has to penetrate vascular walls and reach the interior of tumor cells (Knezevic & Clarke, 2020 ; Wei et al, 2021 ). Many attempts have been made to improve the drug delivery of chemotherapy by enhancing the blood supply of tumor like thermochemotherapy (van Rhoon et al, 2020 ), or trying to normalize chaotic tumor vascular networks (Itatani et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Optimal treatment occasion for ultrasound stimulated microbubbles in promoting gemcitabine delivery to VX2 tumors

et al. 2022

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Ultrasound stimulated microbubbles (USMB) is a widely used technology that can promote chemotherapeutic delivery to tumors yet the best treatment occasion for USMB is unknown or ignored. We aimed to determine the optimal treatment occasion for USMB treatment to enhance tumor chemotherapy to achieve the highest drug concentration in tumors. Experiments were conducted on VX2 tumors implanted in 60 rabbits. Gemcitabine (GEM) was intravenously infused as a chemotherapeutic agent and USMB was administered before, during or after chemotherapy. USMB was conducted with a modified diagnostic ultrasound at 3 MHz employing short bursts (5 cycles and 0.125% duty cycle) at 0.26 MPa in combination with a lipid microbubble. Subsequently, tumor blood perfusion quantitation, drug concentration detection, and fluorescence microscopy were performed. The results showed that the group that received USMB treatment immediately after GEM infusion had the highest drug concentration in tumors, which was 2.83 times that of the control group. Fifteen tumors were then treated repeatedly with the optimal USMB-plus-GEM combination, and along with the GEM and the control groups, were studied for tumor growth, tumor cell proliferation, apoptosis, and related cytokine contents. The combined treatment significantly inhibited tumor growth and promoted apoptosis. The levels of related cytokines, including HIF-1α, decreased after six combination therapies. These results suggest that the optimal treatment occasion for USMB occurs immediately after chemotherapy and tumor hypoxia improves after multiple combination therapies.

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“…Therapeutic drug monitoring (TDM) is the measurement of specific drugs’ stable concentration in a patient’s bloodstream, thereby optimizing individual dosage regimens [ 19 ]. It is commonly and successfully used to ensure appropriate drug exposure and to limit dose-related toxicities [ 20 ]. TDM is cost-effective, and it could be beneficial to personalize a dose to fit the specific needs of cancer patients [ 21 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Quantification of Venetoclax for Therapeutic Drug Monitoring in Chinese Acute Myeloid Leukemia Patients by a Validated UPLC-MS/MS Method

Yang

Chen

et al. 2022

Molecules

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Venetoclax has emerged as a breakthrough for treatment of leukemia with a wide interindividual variability in pharmacokinetics. Herein, a rapid, sensitive, and reliable UPLC-MS/MS method for quantification of venetoclax in plasma was developed and validated. The method was operated in the multiple-reaction monitoring (MRM) mode to detect venetoclax at m/z transition 868.5 > 321.0 and IS at 875.5 > 321.0, respectively. Protein precipitation prior to injection into the LC-MS/MS and the analyte was separated on an ACQUITY UPLC BEH C18 column by gradient elution with acetonitrile and 0.1% formic acid in water. Linear calibration curves were obtained in the range of 25–8000 ng/mL. The specificity, recovery, matrix effect, and stability also met the acceptance criteria of FDA guidance. The method was successfully applied to analyze plasma in acute myeloid leukemia (AML) patients. The peak plasma concentration (Cmax) of venetoclax in Chinese AML patient was 2966.0 ± 1595.0 ng/mL while the trough concentration (Cmin) was 1018.0 ± 729.4 ng/mL. Additionally, Cmax and Cmin showed a positive correlation with AST levels. Furthermore, Cmax was significantly higher in the older patients. The present method can be applied for TDM of venetoclax in treatment of hematological cancers.

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Cancer Chemotherapy: The Case for Therapeutic Drug Monitoring

Cited by 60 publications

References 145 publications

Therapeutic drug monitoring in oncology - What’s out there: A bibliometric evaluation on the topic

Therapeutic drug monitoring in oncology - What’s out there: A bibliometric evaluation on the topic

Optimal treatment occasion for ultrasound stimulated microbubbles in promoting gemcitabine delivery to VX2 tumors

Quantification of Venetoclax for Therapeutic Drug Monitoring in Chinese Acute Myeloid Leukemia Patients by a Validated UPLC-MS/MS Method

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