Cancer Genetics and Epigenetics, 2025, Vol.13, No.3, 126-135 http://medscipublisher.com/index.php/cge 130 these side effects occur more and faster. However, on the whole, these side effects can be controlled. Except for a slightly higher risk of hypertension and some intestinal and gastric problems, the frequency of other side effects is similar to that of chemotherapy alone (Saini and Hurwitz, 2006; Wichelmann et al., 2021; Harjianti et al., 2023; Zeng et al., 2025). 5.2 Mechanisms and risks of severe toxicity Although serious side effects are rare, they can be life-threatening. Intestinal or gastric perforation is a very dangerous situation. Approximately 0.3%~2.4% of patients will encounter it. This is because bevarizumab can prevent blood vessel growth, affecting the repair of gastrointestinal tissue and wound healing (Saini and Hurwitz, 2006; Pavlidis and Pavlidis, 2013; Chitkara et al., 2023). Another 2.6% of the patients had experienced arterial vessel blockage, such as stroke and myocardial infarction. This might be caused by the drugs affecting the integrity of the blood vessels and the function of the inner walls of the blood vessels (Saini and Hurwitz, 2006; Chitkara et al., 2023). Other serious problems include blocked veins and poor healing of surgical wounds. If the patient already has cardiovascular diseases or has just undergone surgery, the possibility of these serious problems occurring is greater. Therefore, be careful when selecting patients and closely observe them during the treatment process (Saini and Hurwitz, 2006; Pavlidis and Pavlidis, 2013; Wichelmann et al., 2021; Chitkara et al., 2023). 5.3 Clinical strategies for side effect prediction, monitoring and management To control the side effects brought by bevacizumab well, it is necessary to keep a close eye on the patient during treatment and deal with the problem immediately as soon as it is found. It is necessary to measure blood pressure frequently. If the blood pressure is high, take medicine immediately to lower it. Before each treatment, it is necessary to check whether there is protein in the urine. If there is too much protein or it does not disappear, it is necessary to consider reducing the dosage of the medicine or stopping the medicine first (Saini and Hurwitz, 2006; Chitkara et al., 2023; Harjianti et al., 2023). To reduce the risk of bleeding, anticoagulant and antiplatelet drugs should be avoided if possible. It is also important to pay close attention to whether the patient shows any signs of bleeding, especially those who have had bleeding problems before. If serious conditions such as perforation of the intestines and stomach or blockage of blood vessels occur, bevacizumab should be stopped immediately, and medication or surgery should be performed depending on the situation. It is very important to explain the risks clearly to patients before treatment, assess the risks in advance, and then formulate the treatment plan according to each person's situation to ensure the safety of treatment and improve the quality of life of patients (Saini and Hurwitz, 2006; Wichelmann et al., 2021; Harjianti et al., 2023; Chitkara et al., 2023). 6 Real-World Data vs. Clinical Trials 6.1 Consistency of efficacy between RCTs and real-world studies Through rigorous comparative trials (RCTs), it was found that bevacizumab combined with chemotherapy in the treatment of metastatic colorectal cancer (mCRC) can prolong the time for patients' conditions to not deteriorate and the overall survival time. Generally speaking, the average time for the condition not to deteriorate is 9 to 12 months, and the total survival time can reach 21 to 28 months. The specific figures depend on the treatment plan and the actual situation of the patient (Waterkamp et al, 2013; Couture et al, 2023). Studies conducted in real hospital treatments have also reached similar conclusions. The time for patients' conditions not to deteriorate and the safety situation are similar, but the overall survival time may be slightly shorter. This may be due to different selected patients, different other diseases of the patients themselves, and the fewer times of using bevacizumab after the condition worsens (Figure 1) (Kim et al., 2020; Lungulescu et al., 2023; Matsumoto et al., 2024). For instance, a large-scale study in Romania found that when patients first started treatment, the average time for their condition not to deteriorate was 8.4 months, and the overall survival time was 17.7 months, which was very close to the results of the comparative trials. A practical study in Japan using FOLFOXIRI combined with bevarizumab showed that the average time for patients' conditions not to deteriorate was 12.8 months, and the
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