Anti-tumor drug TDM effectively reduce adverse reactions occurrence

With the transformation of the modern medical model and the continuous advancement of the new medical reform, hospital pharmacy has undergone epoch-making changes. In the process of transforming from a "drug-centered" to a "patient-centered" pharmaceutical service model, the role of clinical pharmacists has become prominent. In recent years, cancer treatment drugs have developed rapidly. As a large number of anti-tumor drugs have entered the medical insurance, while allowing cancer patients to receive affordable and effective treatment, it has also brought new challenges to clinical pharmacy services. Therapeutic drug monitoring (TDM) can effectively reduce the adverse reactions caused by cancer drugs and provide a favorable guarantee for the safe and rational use of drugs for cancer patients.

Anti-tumor drug TDM effectively reduce adverse reactions occurrence


Anti-tumor drug TDM effectively reduce adverse reactions occurrence

Clinical adverse reactions caused by anti-tumor drugs are still severe in China

A 2017 WHO survey showed that about 10% of patients were harmed due to irrational use of drugs during hospital treatment. Drug injuries caused by irrational use of drugs have become an important public health issue of global concern. According to data from the 2021 "National Adverse Drug Reaction Monitoring Annual Report", there are 1.962 million adverse drug reaction/event reports in China. The number of adverse drug reaction reports nationwide is increasing year by year. Among the chemicals involved in the adverse reaction/event reports, oncology drugs ranked No. 1. Therapeutic drug monitoring plays a very important role in clinical cancer treatment. Through therapeutic drug monitoring technology, cancer patients can be given the most suitable drugs and the most suitable plan, and the occurrence of adverse reactions can be reduced. This is the most fundamental role and significance of therapeutic drug monitoring.

Anti-tumor drug TDM effectively reduce adverse reactions occurrence


Anti-tumor drug TDM effectively reduce adverse reactions occurrence

What is therapeutic drug monitoring (TDM

Therapeutic drug monitoring (TDM) refers to the process of clinical drug treatment, while observing the efficacy of the drug, regularly collecting the patient's body fluids (such as serum), measuring the drug concentration in it. According to the specific situation of the patient, guided by the basic theories of pharmacokinetics and pharmacodynamics, an individualized dosage plan is formulated to improve the efficacy and reduce adverse reactions, thereby achieving safe and effective treatment purposes, and improving clinical medication from traditional empirical treatment model to the level of individualized treatment.

Anti-tumor drug TDM effectively reduce adverse reactions occurrence


Anti-tumor drug TDM effectively reduce adverse reactions occurrence

The necessity of TDM for anti-tumor drugs

The reason why anti-tumor drugs need TDM is first of all because the therapeutic index of anti-tumor drugs is low and the safety range is narrow. When taking the drugs, it is easy to cause insufficient dosage or excessive poisoning. Secondly, blood drug concentration has a strong correlation with drug efficacy and toxicity. The area under the concentration-time curve (AUC) and steady-state blood drug concentration can better reflect drug efficacy and toxicity than the dosage. Thirdly, drug efficacy and toxicity should not be directly observed and screened. For example, chemotherapy drugs usually need to be taken for multiple cycles to determine whether they are effective, and some anti-cancer drugs also have carcinogenic effects. Fourthly, tumors are serious diseases, and their dosage regimen is closely related to the functional level of the patient's heart, liver, kidneys and other organs. Its treatment effect will directly determine the patient's quality of life and even life expectancy. The above characteristics indicate that anti-tumor drugs require close monitoring and timely adjustment of blood drug concentrations. At the same time, individualized medication plans must be formulated based on the patient's own symptoms. TDM will undoubtedly play an important role [1].

Years of practice in foreign oncology pharmacy clinics have proven that pharmacists can reduce or alleviate adverse reactions, improve patients' medication compliance, and improve quality of life through providing pharmaceutical services in outpatient clinics.

Anti-tumor drug TDM effectively reduce adverse reactions occurrence


Anti-tumor drug TDM effectively reduce adverse reactions occurrence

Clinical application of common anti-tumor drugs TDM

Methotrexate (MTX) is recognized as the drug most needed for TDM in the field of oncology. Clinically, MTX monitoring is mainly used to guide leucovorin first aid, but there is no unified standard for monitoring time points and concentration values. The U.S. Food and Drug Administration (FDA) proposes: when MTX is cleared normally, CMTX is approximately 10 μmol/L in 24h, CMTX is approximately 1 μmol/L in 48h, and CMTX is<0.2 μmol/L in 72h. At the same time, define CMTX,
24h ≥ 50 μmol/L or CMTX,
48h ≥ 5 μmol/L as early delayed excretion, CMTX, 72h0.2 μmol/L or CMTX, 96h0.05 μmol/L stands for delayed excretion [4]. Wu Dongyuan et al. [5] summarized the commonly referenced MTX blood concentration monitoring standards in China. Most of them use CMTX,
24h ≤ 10 μmol/L, CMTX, 48h ≤ 1 μmol/L and CMTX, 72h < 0.1 μmol/L. L, and some use CMTX,
44h ≤ 1.0 μmol·L-1 and CMTX, 68h ≤ 0.1 μmol·L-1. A study that recruited 45 patients with primary central nervous system lymphoma [6] found that patients with AUCMTX >1100 μmol·L-1·h had a higher survival rate.

In addition, fluorouracil drugs are represented by 5-fluorouracil (5-FU). A prospective clinical study of 40 patients with colorectal cancer showed [7] that the higher the average plasma 5-FU concentration of the patient, the better the treatment response and survival rate; but when the average plasma concentration of 5-FU was >3000 μg·L -1 or average plasma concentration × infusion duration (C·t) > 24 mg·L -1·h, acute ADR is likely to occur. In addition, for the Mayo regimen of intravenous injection of 5-FU (425 mg·m-2, 2 min), GUSELLA et al. [8] recommended that the optimal AUC cutoff value of 5-FU is 596 mg·L-1 ·min.

Taxane drugs mainly include paclitaxel, docetaxel, and derivatives with taxane skeleton structures. Paclitaxel is mostly used to treat ovarian cancer, breast cancer, and non-small cell lung cancer. The clinical dosage is mostly calculated based on body surface area. The dosage range is 135 to 350 mg·m-2 and the average steady-state plasma concentration is 0.20~8.45 mg·L-1, showing non-linear PK characteristics [11]. JOERGER et al. [12] proposed that the time when the blood drug concentration is greater than 0.05 μmol·L-1 (tc > 0.05 μmol·L-1) is a good predictor of clinical outcome. When tc > 0.05 μmol·L-1 > 61.4h, the patient's disease progression takes a longer time. Many scholars believe [12-13] that tc >0.05μmol·L-1 is related to the decrease of neutrophils. Docetaxel is often administered intravenously, and the recommended dose is 75 mg·m-2 infused for 1 hour every 3 weeks.

Anti-tumor drug TDM is used throughout the entire treatment process, and its restrictions on blood collection time and dosage regimen put forward higher requirements for pharmacists. Clinical pharmacists must do corresponding training and communication work to ensure the accuracy of the data and make meaningful clinical recommendations to guide rational clinical use of medications. It is believed that with the improvement of detection technologies such as chemiluminescence, the recommendation of expert consensus and guidelines, and the further deepening of basic research and clinical research, TDM will be used in more and more anti-tumor treatments.

Diagreat Biotech’s anti-tumor TDM fully-automatic chemiluminescence solution protects tumor patients rational use of drugs

Diagreat Biotech uses advanced chemiluminescence technology and innovatively applies TDM items such as methotrexate, 5-fluorouracil, and paclitaxel to the chemiluminescence platform, forming an innovative anti-tumor TDM solution. Assist cancer patients with accurate diagnosis and treatment. At the same time, Diagreat Biotech chemiluminescence solution realizes fully automatic high-speed detection of samples in and results out, with the advantages of unattended, full-process quality control, and stable and reliable results. Effectively provide clinical individualized precise diagnosis and treatment and complete professional testing services to protect patients' lives and health.

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Anti-tumor drug TDM effectively reduce adverse reactions occurrenceAnti-tumor drug TDM effectively reduce adverse reactions occurrenceAnti-tumor drug TDM effectively reduce adverse reactions occurrenceAnti-tumor drug TDM effectively reduce adverse reactions occurrence

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