Among the top 30 PT reports, general disorders and administration site conditions were the most common, such as application site papules, rash and pruritus. Secondly, skin and subcutaneous tissue disorders, such as dermatitis contact and dermatitis allergic. At the same time, we also found hypertension and the cause of uterine cancer and other adverse reactions. Recent studies have found that several clinical randomized controlled trials have shown that the most common adverse reaction of S-1 is neutropenia[28, 36, 37]. It also includes disorders of the skin system, and gastrointestinal systems such as nausea, vomiting, constipation, and diarrhea[36], which is consistent with the conclusions of many studies[38–40].
Neutropenia, a condition characterized by a decrease in the number of neutrophils, a type of white blood cell that helps fight infections, is a well-documented side effect of many chemotherapy drugs, including S-1. The primary cause of neutropenia in patients receiving S-1 is the drug's impact on the bone marrow, where blood cells are produced. S-1 can suppress the normal production of neutrophils, leading to an increased risk of infections. The gastrointestinal symptoms, such as nausea, vomiting, constipation, and diarrhea, can be attributed to the drug's effect on the gastrointestinal tract. S-1 contains tegafur, a prodrug that is converted to 5-fluorouracil (5-FU) in the body. 5-FU is known to affect the rapidly dividing cells of the gastrointestinal mucosa, which can lead to mucositis and other gastrointestinal disturbances. The dosage and schedule of S-1 administration can also influence the occurrence and severity of these symptoms. Skin reactions associated with S-1 may include rash, itching, or changes in skin color. These can be a result of the drug's impact on the DNA synthesis of rapidly dividing cells, including those of the skin, or an immune response triggered by the drug. As for the less common adverse reactions like hypertension and uterine cancer, the reasons for their occurrence can be multifactorial. Hypertension may occur because of the drug's impact on the cardiovascular system or due to the physiological stress response triggered by the cancer itself and its treatment. The association between S-1 and uterine cancer might be due to the drug's potential to affect the hormonal balance in the body, as some cancer treatments can influence the risk of developing certain types of cancer.
Previously, several clinical center experiments have shown that the common adverse reactions of S-1 include rash, neutropenia, anemia, loss of appetite, diarrhea, etc.[41–43]. This can be explained mainly by the pharmacokinetics before and after drug use. For example, a statistically significant relationship was observed between Cmax and 5-FU concentration before and after treatment[44, 45]. It is important to note that the development of adverse reactions can also be influenced by various patient-related factors, such as underlying health conditions, genetic predisposition, and concurrent medications. Healthcare providers should consider these factors when prescribing S-1 and closely monitor patients for the development of adverse reactions to ensure timely intervention and appropriate management.
Our research has certain limitations, primarily because the FAERS database is an independent reporting system, and the reporting involves doctors, pharmacists, patients, etc., which may lead to false positives in the data mining results. Secondly, whether there is a biological correlation between the target ADE and the drug needs further evaluation by combining case analysis reference to drug instructions, literature reports, and expert opinions. These factors will inevitably result in some deviation in the study's findings, and it is necessary for future studies to conduct comprehensive evaluations based on actual clinical situations.