The following data mainly come from the safety data of this product obtained in clinical trials of advanced hepatocellular carcinoma and advanced renal cell carcinoma, including data from European, American and Asian countries (see clinical trials). Because clinical trials are conducted under various conditions, the incidence of adverse reactions observed in one clinical trial cannot be directly compared with the incidence of adverse reactions observed in other clinical trials, and it cannot reflect the actual observed incidence. Key clinical research safety data supporting the marketing of this product in Europe and America: The most common adverse reactions are diarrhea, rash, alopecia and hand-foot skin reaction (MedDRA corresponds to hand-foot sensory disturbance syndrome). Table 2 comes from 4,565,438+0 renal cancer patients treated with sorafenib as a single drug and 4,565,438+0 renal cancer patients treated with placebo (mainly Caucasian, Including African-Americans, Asian-Americans, Hispanics and other ethnic groups) Table 2: Adverse reactions of at least 5% patients in the treatment group in trial113 (using NCI Table 3: Adverse reactions of at least 5% patients in any treatment group in trial 100554, Terminology and grading standards of common toxic reactions of National Cancer Institute of the United States) Table 4 defines the incidence rate as: very common (≥110) and common (≥1/0) according to different system organs (MedDRA) and frequency of occurrence (according to the guiding principles of the European Drug Administration (EMEA) Human Committee (CHMP) on drug instructions. Ordinary (≥1100, [1/65438] and rare (≥110000, [1/000). Among patients receiving sorafenib, the most common drug-related adverse events were reported as rash (38%), diarrhea (37%), skin reaction of hands and feet (35%) and fatigue (33%). In patients receiving sorafenib, the incidence of grade 3 and grade 4 drug-related adverse events in CTCAE (version 2.0) was 37% and 3%, respectively. More information about adverse drug reactions Congestive heart failure: In the clinical study sponsored by Bayer Company, the incidence of congestive heart failure in patients taking sorafenib was 65,438+0.9% (n = 2,276). In the 1 12 13 study (renal cancer study), the reported incidence of congestive heart failure in sorafenib group and placebo group was 1.7% and 0.7% respectively. In the 100554 study (liver cancer study), the incidence of congestive heart failure in sorafenib group and placebo group was 0.99% and 1. 1% respectively. Bayer's bid is in III? A randomized controlled study comparing the efficacy and safety of carboplatin and paclitaxel+/-sorafenib in patients with stage B-IV non-small cell lung cancer (NSCLC) was terminated prematurely because the Data Monitoring Committee thought that the study could not reach the main end point of prolonging the overall survival. The security incidents in this study are consistent with those reported in previous studies. In patients with lung squamous cell carcinoma, the mortality rate of patients treated with sorafenib plus carboplatin plus paclitaxel was higher than that of patients treated with carboplatin plus paclitaxel only (HR 1.8 1, 95%? CI 1. 19-2.74). The exact reason for this result is not clear. Abnormal laboratory examination Abnormal laboratory examination in patients with renal cell carcinoma (trial 1 12 13): Lipase and amylase usually increase after taking sorafenib. In the study of 1 12 13, the patients in sorafenib group 12% were CTCAE? Grade 3 or 4 lipase increased, which was 7% in the placebo group. In sorafenib group, 1% of patients had increased CT CAE grade or grade 4 amylase, while in placebo group, it was 3%. In the study of 1 12 13, 2 out of 45 1 patients who took sorafenib developed pancreatitis (CTCAE? Grade 4) and 1 case in placebo group (CTCAE? Level 2). Hypophosphatemia is a very common abnormality in laboratory examination. The incidence rate of sorafenib group is 45%, and that of placebo group is 1 1%. The incidence of CTCAE hypophosphatemia (1-2mg/dL) in sorafenib group was 13%, and that in placebo group was 3%. No cases of CTCAE4 grade 4 hypophosphatemia were reported in sorafenib group and placebo group ([1mg/dL). The etiological relationship between hypophosphatemia and sorafenib is unclear. The incidence of CTCAE grade and grade 4 lymphopenia in sorafenib group was 65438 03%, and that in placebo group was 7%. The incidence of neutropenia was 5% in sorafenib group and 2% in placebo group. The incidence of anemia was 2% in sorafenib group and 4% in placebo group. The incidence of thrombocytopenia in sorafenib group was 65438 0%, and that in placebo group was 0%. Abnormal laboratory examination of patients with hepatocellular carcinoma (trial 100554): The incidence of increased lipase in sorafenib group was 40% and that in placebo group was 37%. 9% patients in both groups developed CTCAE? Grade 3 or 4 lipase increased. The incidence of amylase increase in sorafenib group was 34%, and that in placebo group was 29%. It is reported that 2% of patients in both groups have increased CT CAE grade or grade 4 amylase. In many cases, the increase of lipase and amylase is transient, and in most cases, sorafenib treatment will not be interrupted. Of the 297 patients taking sorafenib, 1 patient developed pancreatitis (CT CAE grade). Hypophosphatemia is a common abnormality in laboratory examination. The incidence rate of sorafenib group was 35%, and that of placebo group was 1 1%. CTCAE？ The incidence of grade 3 phosphatemia (1-2mg/dL) in sorafenib group was 1 1%. The incidence in the placebo group was 2%. The placebo group reported 1 case of CTCAE hypophosphatemia ([1 mg/dL). The etiological relationship between hypophosphatemia and sorafenib is unclear. Between the experimental group and the control group, the increase of liver function test indexes is similar. The incidence of AST (aspartate aminotransferase) elevation was 94% in sorafenib group and 9 1% in placebo group. The incidence of CT CAE grade or grade 4 AST elevation was 65,438 06% in sorafenib group and 65,438 07% in placebo group. The incidence of ALT (alanine aminotransferase) elevation in sorafenib group was 69%, and that in placebo group was 68%. CTCAE？ The incidence of grade 3 or 4 ALT elevation was 3% in sorafenib group and 8% in placebo group. The incidence of bilirubin increase in sorafenib group was 47%, and that in placebo group was 45%. The incidence of CT CAE grade or grade 4 bilirubin increase in sorafenib group was 10%, and that in placebo group was 1 1%. The incidence of serum albumin decrease in sorafenib group was 59%, and that in placebo group was 47%. There was no decrease in serum albumin of CT CAE grade or grade 4 in both groups. The incidence of increased alkaline phosphatase in sorafenib group and placebo group was 82.2% and 82.5%, respectively. CTCAE？ The incidence of grade 3 alkaline phosphatase elevation in sorafenib group was 6.2%, and that in placebo group was 8.2%. No increase in alkaline phosphatase of CT CAE grade was observed in both groups. The incidence of INR increase was 42% in sorafenib group and 34% in placebo group. The incidence of CT CAE INR increase in sorafenib group was 4%, and that in placebo group was 2%. The CT CAE INR of both groups did not increase. The incidence of lymphopenia was 47% in sorafenib group and 42% in placebo group. The incidence of grade 3 or 4 lymphopenia in CT CAE of both groups was 6%. The incidence of neutropenia was 1 1% in sorafenib group and 14% in placebo group. The incidence of neutropenia with CT CAE grade or grade 4 in both groups was 65438 0%. The incidence of anemia was 59% in sorafenib group and 64% in placebo group. The incidence of CT CAE grade or grade 4 anemia in both groups was 3%. The incidence of thrombocytopenia was 46% in sorafenib group and 4 1% in placebo group. It is reported that the incidence of CT CAE grade or grade 4 thrombocytopenia in sorafenib group is 4%, and that in placebo group is lower than 1%. Asian safety data: trial 1 15 15 is a non-randomized, non-controlled, open phase II clinical study of sorafenib in the treatment of advanced renal cell carcinoma in Japan. * * * Patients who received sorafenib at least once were 13 1 person. Compared with the key clinical studies in Europe and America, the drug-related adverse events reported in the trial are similar. The most common diseases are increased lipase (56.5%), alopecia (38.9%), increased amylase (38.2%), rash/desquamation (37.4%) and diarrhea (33.6%). Trial 1 1559 is a multicenter, non-randomized phase III clinical study on sorafenib in the treatment of advanced renal cell carcinoma in Asia (including Chinese mainland and Taiwan Province). Among the 39 patients who received sorafenib treatment at least once, 36 (92.3%) had drug-related adverse events. The common adverse events were skin reaction of hands and feet (64.65438 0%), alopecia (35.9%), diarrhea (28.2%) and pain (23.65438 0%). Table 5 lists the drug-related adverse events with an incidence of at least 5% and ≥3. Of all the patients who received treatment, 10 patients * * * had 16 serious adverse events (SAE), among which 5 incidents of 3 patients were judged to be related to the study drug by researchers and Bayer headquarters, but the severity was ≤ CTCAE level 3. Table 5: The incidence of drug-related adverse events ≥3 in trial 1 1559 is at least 5%. Trial 1 1849 is an international multicenter, randomized, placebo-controlled phase III clinical trial of sorafenib in the treatment of advanced hepatocellular carcinoma in Asia (including Chinese mainland, Taiwan Province and South Korea). Of all 149 patients who received sorafenib at least once, 12 1 patient (8 1.2%) had drug-related adverse events. In addition to nausea and vomiting, the researchers judged that the incidence of drug-related adverse events in sorafenib group was significantly higher than that in placebo group. The five most common adverse drug reactions in sorafenib group were: hand and foot skin reaction (44.3%), alopecia (24.2%), diarrhea (22.8%), rash (18.8%) and fatigue (18.8%). Table 6 lists the drug-related adverse reactions observed in the study with an incidence of ≥5%. Table 6: As of March 1 1849, there were 95 cases in serious adverse events, 32 cases in placebo group (42.7%) and 63 cases in sorafenib group (42.3%). Among them, there were 20 cases in serious adverse events, placebo group 1 case (1.3%) and sorafenib group 19 cases (12.7%). Except for 2 cases of upper gastrointestinal bleeding (grade 4) and 1 pneumonia (grade 5), all serious adverse events related to sorafenib were ≤CTCAE? Level three. Table 7 shows serious adverse events related to sorafenib. Table 7: serious adverse events incidence rate of at least 1% patients in any treatment group in trial1849 during treatment.