TDM brings terminal colorectal cancer treatment into a new era!
发布日期：
2024-07-22
浏览次数：
0





5-Fu TDM



Chemotherapy is the main treatment modality for patients with advanced colorectal cancer, and the combination of 5-fluorouracil (5-Fu) and calcium folinate is the most commonly used chemotherapy regimen in the clinic. Clinicians usually calculate the dosage of 5-Fu based on the patient's body surface area (mg/m2). Kaldate et al showed that in metastatic colorectal cancer patients, the area under the curve (AUC) of the optimal blood concentration based on the evaluation of the toxicity and efficacy of 5-Fu was 25 mg·h/L, and the optimal therapeutic window of 5-Fu was recognized to be between 20-30 mg·h/L. The present study showed that 5-Fu is the most commonly used chemotherapy regimen, and it is not possible to determine the dose of 5-Fu in patients with metastatic colorectal cancer. Compared with the traditional body surface area (BSA) drug delivery method, the present study shows that blood concentration monitoring can optimize the dosage of 5-Fu in the treatment of advanced colorectal cancer, so that the dosage of 5-Fu can be more accurately formulated for individual patients to achieve the effect of individualized and precise chemotherapy.


TDM brings terminal colorectal cancer treatment into a new era!

Result 1: 

AUC Distribution of 5-Fu Blood Concentration and Pharmacokinetic Parameters


The results of 5-Fu blood concentration analysis in the control group and the experimental group during the 6 cycles showed that the proportion of the 37 patients in the control group who fell within the therapeutic window (AUC:20-30 mg·h/L) for a total of 23 times during the 6 cycles was 16.67% (23/138), and most of the patients had a 5-Fu AUC value lower than the therapeutic window range. In the experimental group, after BSA-based administration, the distribution of 5-Fu blood concentration was also more dispersed, and the proportion of patients falling within the therapeutic window was 21.6% (8/37) with a coefficient of variation (CV) of 48.77% in cycle 1, and after dose adjustment from cycle 2 to 6, the proportion increased to 67.74% (23/34) with a CV of 22.75% in cycle 6. The difference between the two groups was statistically significant (χ2 = 20.04, P < 0.01).

TDM brings terminal colorectal cancer treatment into a new era!


Figure 1 AUC distribution of 5-Fu over 6 cycles in control and experimental patients

Note, A, the majority of patients in the control group had 5-Fu AUC values below the therapeutic window range; B, there was an increase in the number of patients in the experimental group whose 5-Fu AUC fell within the therapeutic window range, with a tendency to concentrate.

Result 2:

 Relationship between 5-Fu toxicity and dose adjustment





Compared with the control group [70.3% (26/37)], the incidence of toxic side effects ( ≥ grade 3) in the experimental group [32.4% (12/37)] showed a statistically significant difference (χ2 = 10.60, P < 0.01). Further analysis of the specific toxic side effects showed that the differences in diarrhea, oral mucositis and other toxic side effects were statistically significant (P < 0.05), while the differences in nausea, vomiting, hand-foot syndrome, loss of appetite, loss of body weight and leukopenia were not statistically significant (P > 0.05).

Table 2 Relationship between toxic side effects in control and experimental groups [n (%)]

TDM brings terminal colorectal cancer treatment into a new era!







Discussion


Clinical trials have shown that in the field of colorectal cancer treatment, the reduction of toxicity and the increase of therapeutic effect can be achieved by routine blood concentration monitoring of 5-Fu and individualized dosage adjustment according to the pharmacological profile of each patient.The effective therapeutic concentration range (therapeutic window) of 5-Fu is very narrow, and differences in the metabolism of the drug by patients can give rise to large differences in individual pharmacodynamics. Therefore, there is an urgent need to monitor the blood concentration and dose adjustment of 5-Fu based on individual pharmacological differences.
From the comparison of the results of this study, it can be seen that timely adjustment of patients' dosage through 5-Fu blood concentration detection can increase the proportion of patients falling within the therapeutic window in the experimental group, indicating that dose management of 5-Fu through pharmacokinetics is a clinically feasible operation. The dosage adjustment made the patients reach the set therapeutic window blood concentration range, which not only did not reduce the therapeutic effect, but also had better overall toxicity control than the BSA administration method.
In addition, since the test is to detect the blood concentration of 5-Fu in the process of intravenous continuous titration, the metabolism of 5-Fu in the subsequent continuous titration process can be predicted based on the timely test report, and the duration of the titration can be adjusted according to the patient's own state and the test results, in order to control the toxic reactions related to chemotherapy or to improve the therapeutic efficacy of the chemotherapy.




References:

［1］Lee JJ，Beumer JH，Chu E． Therapeutic drug monitoring of 5 fluorouracil［J］． Cancer Chemother Pharmacol，2016，78( 3) : 447-464．

［2］Kaldate RR，Haregewoin A，Grier CE，et al． Modeling the 5-fluorouracil area under the curve versus dose relationship to develop a pharmacokinetic dosing algorithm for colorectal cancer patients receiving FOLFOX6［J］. Oncologist，2012，17( 3) : 296-302．

［3］Eisenhauer EA，Therasse P，Bogaerts J，et al． New response evaluation criteria in solid tumours: revised RECIST guideline ( version 1.1) ［J］． Eur J Cancer，2009，45( 2) : 228-247．

［4］石远凯，孙燕． 临床肿瘤内科手册［M］．第 6 版． 北京: 人民卫生 出版社，2015: 88-117

Diagreat

Therapeutic Drug Monitoring - Fully Automated Chemiluminescent Solution


Based on the chemiluminescence platform, Diagreat provides blood concentration monitoring packages for several series of antitumor drugs, antibiotics, immunosuppressants, antipsychotics, cardiac glycosides drugs, and antiasthmatic drugs. Among them, the anti-tumor drugs include paclitaxel and methotrexate in addition to 5-Fu, which play an important role in the safe use of drugs in the clinic and the reduction of toxic side effects. Diagreat instruments are characterized by high degree of automation, rapid, high throughput, stable operation, superior performance and perfect traceability, etc., which can provide complete solutions for users at different levels.

TDM brings terminal colorectal cancer treatment into a new era!

TDM brings terminal colorectal cancer treatment into a new era!

TDM brings terminal colorectal cancer treatment into a new era!



Ordering Information







Last：Association between levels of MPA and complications in SLENext：Combination of personalized medicine and digoxin monitoring

Related Recommendations