Background:As a novel blocker of vascular endothelial growth factor receptor(VEGFR),fruquintinib has been approved for treating colorectal cancer(CRC).However,its dosage and therapeutic efficacy are limited by its wid...Background:As a novel blocker of vascular endothelial growth factor receptor(VEGFR),fruquintinib has been approved for treating colorectal cancer(CRC).However,its dosage and therapeutic efficacy are limited by its widespread adverse reactions.Venetoclax,recognized as the initial inhibitor of B-cell lymphoma protein 2(BCL2),has shown potential in boosting the effectiveness of immunotherapy against CRC.This study investigated the efficacy and mechanisms of fruquintinib combined with venetoclax in treating CRC.Methods and Materials:We developed a colon cancer mouse model with the CT26 colon cell line to demonstrate fruquintinib and venetoclax’s efficacy against tumors.Then we employed various techniques to evaluate different aspects of the experimental outcomes.Immunohistochemistry was used to detect cell proliferation and angiogenesis in tumor tissues.Western blot analysis was utilized to examine the occurrence of cell apoptosis,and flow cytometry to quantitate immune cells within the tumor tissues.Moreover,immunofluorescence was employed to measure cytokine levels.Results:The strongest inhibition on tumor growth was achieved by the combination of fruquintinib with venetoclax,as opposed to individual drug use.Venetoclax was found to amplify the impact of fruquintinib,leading to decreased cancer cell proliferation,increased cancer cell apoptosis,lowered angiogenesis,better vascular structure normalization,and improved immune cell infiltration.Conclusion:Our findings indicate that the addition of venetoclax enhances the impact of fruquintinib on vascular normalization and modulation of the tumor immune microenvironment.Our study presents the justification for utilizing the fruquintinib and venetoclax combination in treating CRC.Venetoclax holds promise in being assimilated into anticancer medications for CRC.展开更多
BACKGROUND Immune checkpoint inhibitors have demonstrated significant efficacy in colorectal cancer(CRC)patients with microsatellite instability-high or deficient mismatch repair.However,their efficacy as monotherapy ...BACKGROUND Immune checkpoint inhibitors have demonstrated significant efficacy in colorectal cancer(CRC)patients with microsatellite instability-high or deficient mismatch repair.However,their efficacy as monotherapy is limited in microsatellite stable/proficient mismatch repair(MSS/pMMR)subtypes.AIM To provide an evidence-based rationale for optimizing later-line therapeutic strategies in advanced MSS/pMMR CRC.METHODS This study conducted a systematic retrospective analysis to evaluate the efficacy and safety of a triple-combination regimen comprising programmed death 1 inhibitors,fruquintinib and docetaxel administered as third-line therapy in 13 patients with advanced MSS/pMMR CRC.RESULTS Primary endpoints included progression-free survival and disease control rate.Intention-to-treat analysis showed median progression-free survival 7.0 months,median overall survival 18.5 months,disease control rate 61.5%,with manageable toxicity.CONCLUSION Although this is a small-sample retrospective study,it preliminarily validates the synergistic effect of programmed death 1 inhibitors combined with fruquintinib and docetaxel in MSS/pMMR CRC,providing a novel strategy with translational significance for later-line treatment in advanced patients.展开更多
BACKGROUND PD-1 inhibitors in combination with fruquintinib have not previously been reported as neoadjuvant therapy for patients with colorectal cancer.In this case report,the combination of a PD-1 inhibitor and fruq...BACKGROUND PD-1 inhibitors in combination with fruquintinib have not previously been reported as neoadjuvant therapy for patients with colorectal cancer.In this case report,the combination of a PD-1 inhibitor and fruquintinib demonstrated good efficacy in patients with MSI-H colorectal cancer.CASE SUMMARY The patient was a young man in his 30s who had MSI-H type colon cancer.The patient underwent four cycles of neoadjuvant therapy with a PD-1 inhibitor combined with fruquintinib before surgery,resulting in regression of the mass and a successful surgery.CONCLUSION Some patients with colorectal cancer have the MSI-H type,and the first-line chemotherapy regimen is not effective.However,PD-1 monoclonal antibody immunotherapy has a good therapeutic effect,which can be improved by combination therapy with fruquintinib.We recommend that patients with a history of colon or rectal cancer receive universal MSI testing;then,neoadjuvant therapy should be used.展开更多
BACKGROUND Regorafenib(R)and fruquintinib(F)are the standard third-line regimens for colorectal cancer(CRC)according to the National Comprehensive Cancer Network guidelines,but both have limited efficacy.Several phase...BACKGROUND Regorafenib(R)and fruquintinib(F)are the standard third-line regimens for colorectal cancer(CRC)according to the National Comprehensive Cancer Network guidelines,but both have limited efficacy.Several phase 2 trials have indicated that R or F combined with immune checkpoint inhibitors can reverse immunosuppression and achieve promising efficacy for microsatellite stable or proficient mismatch repair(MSS/pMMR)CRC.Due to the lack of studies comparing the efficacy between F,R,F plus programmed death-1(PD-1)inhibitor,and R plus PD-1 inhibitors(RP),it is still unclear whether the combination therapy is more effective than monotherapy.AIM To provide critical evidence for selecting the appropriate drugs for MSS/pMMR metastatic CRC(mCRC)patients in clinical practice.METHODS A total of 2639 CRC patients were enrolled from January 2018 to September 2022 in our hospital,and 313 MSS/pMMR mCRC patients were finally included.RESULTS A total of 313 eligible patients were divided into F(n=70),R(n=67),F plus PD-1 inhibitor(FP)(n=95)and RP(n=81)groups.The key clinical characteristics were well balanced among the groups.The median progression-free survival(PFS)of the F,R,FP,and RP groups was 3.5 months,3.6 months,4.9 months,and 3.0 months,respectively.The median overall survival(OS)was 14.6 months,15.7 months,16.7 months,and 14.1 months.The FP regimen had an improved disease control rate(DCR)(P=0.044)and 6-month PFS(P=0.014)and exhibited a better trend in PFS(P=0.057)compared with F,and it was also significantly better in PFS than RP(P=0.030).RP did not confer a significant survival benefit;instead,the R group had a trend toward greater benefit with OS(P=0.080)compared with RP.No significant differences were observed between the R and F groups in PFS or OS(P>0.05).CONCLUSION FP is superior to F in achieving 6-month PFS and DCR,while RP is not better than R.FP has an improved PFS and 6-month PFS compared with RP,but F and R had similar clinical efficacy.Therefore,FP may be a highly promising strategy in the treatment of MSS/pMMR mCRC.展开更多
BACKGROUND After the failure of second-line standard therapy,effective treatment options for metastatic colorectal cancer are limited,and the duration of remission cannot meet clinical needs.In addition,associated dru...BACKGROUND After the failure of second-line standard therapy,effective treatment options for metastatic colorectal cancer are limited,and the duration of remission cannot meet clinical needs.In addition,associated drug toxicity may lead to treatment interruption that may affect patient outcomes.Therefore,more safe,effective and convenient treatments are urgently needed.CASE SUMMARY Here,we describe a patient with advanced colorectal cancer with multiple metastases in both lungs.Oxaliplatin combined with 5-fluorouracil or capecitabine was given as the first-line treatment,and bevacizumab combined with irinotecan was given as the second-line treatment after disease progression.However,treatment was interrupted due to recurrent grade 2 nausea and grade 1 diarrhea.He received targeted therapy with fruquintinib starting on August 26,2020 and responded well for 12 mo.After slow progression of the lung metastases,progression-free survival was again achieved over 13.5 mo by continued treatment of fruquintinib in combination with tegafur-gimeracil-oteracil potassium chemotherapy.Overall treatment duration was more than 25.5 mo.The treatments delayed tumor progression,reduced drug side effects,maintained a good quality of life,and further extended overall survival.CONCLUSION This case report detailed preliminary evidence showing that the combination of fruquintinib with tegafur-gimeracil-oteracil potassium chemotherapy double oral therapy may result in longer progression-free survival in patients with advanced colorectal cancer.展开更多
BACKGROUND Neoplastic pericardial effusion(NPE)is a rare consequence of rectal cancer and carries a poor prognosis.Optimal management has yet to be determined.Fruquintinib is an oral anti-vascular endothelial growth f...BACKGROUND Neoplastic pericardial effusion(NPE)is a rare consequence of rectal cancer and carries a poor prognosis.Optimal management has yet to be determined.Fruquintinib is an oral anti-vascular endothelial growth factor receptor tyrosine kinase inhibitor approved by the China Food and Drug Administration in September 2018 as third-line treatment of metastatic colorectal cancer.CASE SUMMARY Herein,we report an elderly patient with NPE from rectal cancer who responded to the use of fruquintinib.In March 2015,a 65-year-old Chinese woman diagnosed with KRAS-mutated adenocarcinoma of the rectum was subjected to proctectomy,adjuvant concurrent chemoradiotherapy,and adjuvant chemotherapy.By October 2018,a mediastinal mass was detected via computed tomography.The growth had invaded parietal pericardium and left hilum,displaying features of rectal adenocarcinoma in a bronchial biopsy.FOLFIRI and FOLFOX chemotherapeutic regimens were administered as first-and second-line treatments.After two cycles of second-line agents,a sizeable pericardial effusion resulting in tamponade was drained by pericardial puncture.Fluid cytology showed cells consistent with rectal adenocarcinoma.Single-agent fruquintinib was initiated on January 3,2019,as a third-line therapeutic.Ten cycles were delivered before the NPE recurred and other lesions progressed.The recurrence-free interval for NPE was 9.2 mo,attesting to the efficacy of fruquintinib.Ultimately,the patient entered a palliative care unit for best supportive care.CONCLUSION Fruquintinib may confer good survival benefit in elderly patients with NPEs due to rectal cancer.展开更多
BACKGROUND Pancreatic cancer is a highly malignant disease.After decades of treatment progress,the current five-year survival rate for patients is still less than 10%.For later-line treatment,the treatment options are...BACKGROUND Pancreatic cancer is a highly malignant disease.After decades of treatment progress,the current five-year survival rate for patients is still less than 10%.For later-line treatment,the treatment options are even more limited.Anti-angiogenic drugs can improve progression-free survival in patients with advanced pancreatic cancer.Preclinical data show that fruquintinib might improve the prognosis of advanced pancreatic cancer by targeting angiogenesis and lymphopoiesis,improving the abnormal vascular structure,and modulating the tumour immune microenvironment.CASE SUMMARY We present two cases of third-line fruquintinib monotherapy that brought an extraprolonged progress-free survival(PFS)of 10 months.Patient 1 took adjuvant gemcitabine-based and first-line nab-paclitaxel-based chemotherapy and then used local radiotherapy combined with programmed cell death 1 receptor(PD-1).Each line lasted approximately 7 months.Moreover,the patient took third-line fruquintinib,which was followed by stable disease for 10 months,during which no additional adverse effect was observed.The patient later refused to take fruquintinib due to difficulty urinating and lower abdominal pain after the coronavirus disease 2019(COVID-19)infection.The patient died in February 2023.Patient 2 also took two prior lines of chemotherapy and then local radiotherapy combined with S-1.After confirmed disease progression,the patient experienced a continuous partial response after using fruquintinib monotherapy in the third line.After the patient had COVID-19 in December 2022,fruquintinib was discontinued.The patient died in January 2023 due to disease progression.CONCLUSION Both cases achieved a PFS benefit from later-line single-agent fruquintinib therapy.With its better safety profile,fruquintinib may be worth exploring and studying in more depth as a later-line treatment for pancreatic cancer patients.展开更多
背景38.4%的结直肠癌患者死于非癌症疾病,其中心血管疾病是最主要原因,占总死亡人数的20.3%。靶向治疗相关的心血管毒性并不少见,最突出的为高血压。目的本研究旨在探讨转移性结直肠癌患者呋喹替尼治疗相关心血管毒性的发生率和风险。...背景38.4%的结直肠癌患者死于非癌症疾病,其中心血管疾病是最主要原因,占总死亡人数的20.3%。靶向治疗相关的心血管毒性并不少见,最突出的为高血压。目的本研究旨在探讨转移性结直肠癌患者呋喹替尼治疗相关心血管毒性的发生率和风险。方法系统检索中国知网、万方数据知识服务平台、中国生物医学文献数据库、Web of Science、PubMed、Cochrane Library、Embase数据库中有关转移性结直肠癌患者呋喹替尼治疗的单臂临床试验和随机对照试验,检索时限为建库至2024年5月。由2名研究者独立进行文献筛选、资料提取及质量评价,使用R 4.3.3软件进行Meta分析。结果共纳入8篇文献,涉及6项单臂临床试验、3项随机对照试验。Meta分析结果显示:全级别高血压和出血的发生率为35%(95%CI=0.25~0.45)和24%(95%CI=0.10~0.37)。在高级别事件中,高血压发生率为15%(95%CI=0.10~0.20),出血发生率为1%(95%CI=0~0.02),血栓栓塞发生率为3%(95%CI=0.02~0.05),心脏疾病发生率为1%(95%CI=0~0.02)。呋喹替尼与全级别、高级别高血压及全级别出血的风险增加相关,RR分别为3.93(95%CI=2.95~5.24)、12.33(95%CI=5.31~28.63)及1.84(95%CI=1.36~2.50),但与高级别的出血(RR=1.06,95%CI=0.35~3.23)、血栓栓塞事件(RR=3.35,95%CI=0.89~12.55)及心脏疾病(RR=0.62,95%CI=0.18~2.14)无关。结论呋喹替尼与转移性结直肠癌患者心血管毒性发生率和风险增加显著相关,但主要针对的是低级别事件。展开更多
基金supported by the National Natural Science Foundation of China(82072675,82273197,82173933)Fundamental Research Funds for the Central Universities(020814380160).
文摘Background:As a novel blocker of vascular endothelial growth factor receptor(VEGFR),fruquintinib has been approved for treating colorectal cancer(CRC).However,its dosage and therapeutic efficacy are limited by its widespread adverse reactions.Venetoclax,recognized as the initial inhibitor of B-cell lymphoma protein 2(BCL2),has shown potential in boosting the effectiveness of immunotherapy against CRC.This study investigated the efficacy and mechanisms of fruquintinib combined with venetoclax in treating CRC.Methods and Materials:We developed a colon cancer mouse model with the CT26 colon cell line to demonstrate fruquintinib and venetoclax’s efficacy against tumors.Then we employed various techniques to evaluate different aspects of the experimental outcomes.Immunohistochemistry was used to detect cell proliferation and angiogenesis in tumor tissues.Western blot analysis was utilized to examine the occurrence of cell apoptosis,and flow cytometry to quantitate immune cells within the tumor tissues.Moreover,immunofluorescence was employed to measure cytokine levels.Results:The strongest inhibition on tumor growth was achieved by the combination of fruquintinib with venetoclax,as opposed to individual drug use.Venetoclax was found to amplify the impact of fruquintinib,leading to decreased cancer cell proliferation,increased cancer cell apoptosis,lowered angiogenesis,better vascular structure normalization,and improved immune cell infiltration.Conclusion:Our findings indicate that the addition of venetoclax enhances the impact of fruquintinib on vascular normalization and modulation of the tumor immune microenvironment.Our study presents the justification for utilizing the fruquintinib and venetoclax combination in treating CRC.Venetoclax holds promise in being assimilated into anticancer medications for CRC.
文摘BACKGROUND Immune checkpoint inhibitors have demonstrated significant efficacy in colorectal cancer(CRC)patients with microsatellite instability-high or deficient mismatch repair.However,their efficacy as monotherapy is limited in microsatellite stable/proficient mismatch repair(MSS/pMMR)subtypes.AIM To provide an evidence-based rationale for optimizing later-line therapeutic strategies in advanced MSS/pMMR CRC.METHODS This study conducted a systematic retrospective analysis to evaluate the efficacy and safety of a triple-combination regimen comprising programmed death 1 inhibitors,fruquintinib and docetaxel administered as third-line therapy in 13 patients with advanced MSS/pMMR CRC.RESULTS Primary endpoints included progression-free survival and disease control rate.Intention-to-treat analysis showed median progression-free survival 7.0 months,median overall survival 18.5 months,disease control rate 61.5%,with manageable toxicity.CONCLUSION Although this is a small-sample retrospective study,it preliminarily validates the synergistic effect of programmed death 1 inhibitors combined with fruquintinib and docetaxel in MSS/pMMR CRC,providing a novel strategy with translational significance for later-line treatment in advanced patients.
文摘BACKGROUND PD-1 inhibitors in combination with fruquintinib have not previously been reported as neoadjuvant therapy for patients with colorectal cancer.In this case report,the combination of a PD-1 inhibitor and fruquintinib demonstrated good efficacy in patients with MSI-H colorectal cancer.CASE SUMMARY The patient was a young man in his 30s who had MSI-H type colon cancer.The patient underwent four cycles of neoadjuvant therapy with a PD-1 inhibitor combined with fruquintinib before surgery,resulting in regression of the mass and a successful surgery.CONCLUSION Some patients with colorectal cancer have the MSI-H type,and the first-line chemotherapy regimen is not effective.However,PD-1 monoclonal antibody immunotherapy has a good therapeutic effect,which can be improved by combination therapy with fruquintinib.We recommend that patients with a history of colon or rectal cancer receive universal MSI testing;then,neoadjuvant therapy should be used.
文摘BACKGROUND Regorafenib(R)and fruquintinib(F)are the standard third-line regimens for colorectal cancer(CRC)according to the National Comprehensive Cancer Network guidelines,but both have limited efficacy.Several phase 2 trials have indicated that R or F combined with immune checkpoint inhibitors can reverse immunosuppression and achieve promising efficacy for microsatellite stable or proficient mismatch repair(MSS/pMMR)CRC.Due to the lack of studies comparing the efficacy between F,R,F plus programmed death-1(PD-1)inhibitor,and R plus PD-1 inhibitors(RP),it is still unclear whether the combination therapy is more effective than monotherapy.AIM To provide critical evidence for selecting the appropriate drugs for MSS/pMMR metastatic CRC(mCRC)patients in clinical practice.METHODS A total of 2639 CRC patients were enrolled from January 2018 to September 2022 in our hospital,and 313 MSS/pMMR mCRC patients were finally included.RESULTS A total of 313 eligible patients were divided into F(n=70),R(n=67),F plus PD-1 inhibitor(FP)(n=95)and RP(n=81)groups.The key clinical characteristics were well balanced among the groups.The median progression-free survival(PFS)of the F,R,FP,and RP groups was 3.5 months,3.6 months,4.9 months,and 3.0 months,respectively.The median overall survival(OS)was 14.6 months,15.7 months,16.7 months,and 14.1 months.The FP regimen had an improved disease control rate(DCR)(P=0.044)and 6-month PFS(P=0.014)and exhibited a better trend in PFS(P=0.057)compared with F,and it was also significantly better in PFS than RP(P=0.030).RP did not confer a significant survival benefit;instead,the R group had a trend toward greater benefit with OS(P=0.080)compared with RP.No significant differences were observed between the R and F groups in PFS or OS(P>0.05).CONCLUSION FP is superior to F in achieving 6-month PFS and DCR,while RP is not better than R.FP has an improved PFS and 6-month PFS compared with RP,but F and R had similar clinical efficacy.Therefore,FP may be a highly promising strategy in the treatment of MSS/pMMR mCRC.
文摘BACKGROUND After the failure of second-line standard therapy,effective treatment options for metastatic colorectal cancer are limited,and the duration of remission cannot meet clinical needs.In addition,associated drug toxicity may lead to treatment interruption that may affect patient outcomes.Therefore,more safe,effective and convenient treatments are urgently needed.CASE SUMMARY Here,we describe a patient with advanced colorectal cancer with multiple metastases in both lungs.Oxaliplatin combined with 5-fluorouracil or capecitabine was given as the first-line treatment,and bevacizumab combined with irinotecan was given as the second-line treatment after disease progression.However,treatment was interrupted due to recurrent grade 2 nausea and grade 1 diarrhea.He received targeted therapy with fruquintinib starting on August 26,2020 and responded well for 12 mo.After slow progression of the lung metastases,progression-free survival was again achieved over 13.5 mo by continued treatment of fruquintinib in combination with tegafur-gimeracil-oteracil potassium chemotherapy.Overall treatment duration was more than 25.5 mo.The treatments delayed tumor progression,reduced drug side effects,maintained a good quality of life,and further extended overall survival.CONCLUSION This case report detailed preliminary evidence showing that the combination of fruquintinib with tegafur-gimeracil-oteracil potassium chemotherapy double oral therapy may result in longer progression-free survival in patients with advanced colorectal cancer.
文摘BACKGROUND Neoplastic pericardial effusion(NPE)is a rare consequence of rectal cancer and carries a poor prognosis.Optimal management has yet to be determined.Fruquintinib is an oral anti-vascular endothelial growth factor receptor tyrosine kinase inhibitor approved by the China Food and Drug Administration in September 2018 as third-line treatment of metastatic colorectal cancer.CASE SUMMARY Herein,we report an elderly patient with NPE from rectal cancer who responded to the use of fruquintinib.In March 2015,a 65-year-old Chinese woman diagnosed with KRAS-mutated adenocarcinoma of the rectum was subjected to proctectomy,adjuvant concurrent chemoradiotherapy,and adjuvant chemotherapy.By October 2018,a mediastinal mass was detected via computed tomography.The growth had invaded parietal pericardium and left hilum,displaying features of rectal adenocarcinoma in a bronchial biopsy.FOLFIRI and FOLFOX chemotherapeutic regimens were administered as first-and second-line treatments.After two cycles of second-line agents,a sizeable pericardial effusion resulting in tamponade was drained by pericardial puncture.Fluid cytology showed cells consistent with rectal adenocarcinoma.Single-agent fruquintinib was initiated on January 3,2019,as a third-line therapeutic.Ten cycles were delivered before the NPE recurred and other lesions progressed.The recurrence-free interval for NPE was 9.2 mo,attesting to the efficacy of fruquintinib.Ultimately,the patient entered a palliative care unit for best supportive care.CONCLUSION Fruquintinib may confer good survival benefit in elderly patients with NPEs due to rectal cancer.
基金Supported by Found by the General Program of Wuxi Health and Health Committee,No.MS201908.
文摘BACKGROUND Pancreatic cancer is a highly malignant disease.After decades of treatment progress,the current five-year survival rate for patients is still less than 10%.For later-line treatment,the treatment options are even more limited.Anti-angiogenic drugs can improve progression-free survival in patients with advanced pancreatic cancer.Preclinical data show that fruquintinib might improve the prognosis of advanced pancreatic cancer by targeting angiogenesis and lymphopoiesis,improving the abnormal vascular structure,and modulating the tumour immune microenvironment.CASE SUMMARY We present two cases of third-line fruquintinib monotherapy that brought an extraprolonged progress-free survival(PFS)of 10 months.Patient 1 took adjuvant gemcitabine-based and first-line nab-paclitaxel-based chemotherapy and then used local radiotherapy combined with programmed cell death 1 receptor(PD-1).Each line lasted approximately 7 months.Moreover,the patient took third-line fruquintinib,which was followed by stable disease for 10 months,during which no additional adverse effect was observed.The patient later refused to take fruquintinib due to difficulty urinating and lower abdominal pain after the coronavirus disease 2019(COVID-19)infection.The patient died in February 2023.Patient 2 also took two prior lines of chemotherapy and then local radiotherapy combined with S-1.After confirmed disease progression,the patient experienced a continuous partial response after using fruquintinib monotherapy in the third line.After the patient had COVID-19 in December 2022,fruquintinib was discontinued.The patient died in January 2023 due to disease progression.CONCLUSION Both cases achieved a PFS benefit from later-line single-agent fruquintinib therapy.With its better safety profile,fruquintinib may be worth exploring and studying in more depth as a later-line treatment for pancreatic cancer patients.
文摘背景38.4%的结直肠癌患者死于非癌症疾病,其中心血管疾病是最主要原因,占总死亡人数的20.3%。靶向治疗相关的心血管毒性并不少见,最突出的为高血压。目的本研究旨在探讨转移性结直肠癌患者呋喹替尼治疗相关心血管毒性的发生率和风险。方法系统检索中国知网、万方数据知识服务平台、中国生物医学文献数据库、Web of Science、PubMed、Cochrane Library、Embase数据库中有关转移性结直肠癌患者呋喹替尼治疗的单臂临床试验和随机对照试验,检索时限为建库至2024年5月。由2名研究者独立进行文献筛选、资料提取及质量评价,使用R 4.3.3软件进行Meta分析。结果共纳入8篇文献,涉及6项单臂临床试验、3项随机对照试验。Meta分析结果显示:全级别高血压和出血的发生率为35%(95%CI=0.25~0.45)和24%(95%CI=0.10~0.37)。在高级别事件中,高血压发生率为15%(95%CI=0.10~0.20),出血发生率为1%(95%CI=0~0.02),血栓栓塞发生率为3%(95%CI=0.02~0.05),心脏疾病发生率为1%(95%CI=0~0.02)。呋喹替尼与全级别、高级别高血压及全级别出血的风险增加相关,RR分别为3.93(95%CI=2.95~5.24)、12.33(95%CI=5.31~28.63)及1.84(95%CI=1.36~2.50),但与高级别的出血(RR=1.06,95%CI=0.35~3.23)、血栓栓塞事件(RR=3.35,95%CI=0.89~12.55)及心脏疾病(RR=0.62,95%CI=0.18~2.14)无关。结论呋喹替尼与转移性结直肠癌患者心血管毒性发生率和风险增加显著相关,但主要针对的是低级别事件。
