PDF(Pubmed)
Abstract：
BACKGROUND: Due to encouraging pre-clinical data and supportive observational studies, there has been growing interest in applying cardiovascular drugs (including aspirin, angiotensin-converting enzyme [ACE] inhibitors, statins, and metformin) approved to treat diseases such as hypertension, hyperlipidemia, and diabetes mellitus to the field of oncology. Moreover, given growing costs with cancer care, these medications have offered a potentially more affordable avenue to treat or prevent recurrence of cancer. We sought to investigate the anti-cancer effects of drugs repurposed from cardiology or anti-inflammatories to treat cancer. We specifically evaluated the following drug classes: HMG-CoA reductase inhibitors (statins), cyclo-oxygenase inhibitors, aspirin, metformin, and both angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors. We also included non-steroidal anti-inflammatory drugs (NSAIDs) because they exert a similar mechanism to aspirin by blocking prostaglandins and reducing inflammation that is thought to promote the development of cancer.
METHODS: We performed a systematic literature review using PubMed and Web of Science with search terms including \"aspirin,\" \"NSAID,\" \"statin\" (including specific statin drug names), \"metformin,\" \"ACE inhibitors,\" and \"ARBs\" (including specific anti-hypertensive drug names) in combination with \"cancer.\" Searches were limited to human studies published between 2000 and 2023.
METHODS: The number and percentage of studies reported positive results and pooled estimates of overall survival, progression-free survival, response, and disease-free survival.
RESULTS: We reviewed 3094 titles and included 67 randomized clinical trials. The most common drugs that were tested were metformin (n = 21; 30.9%), celecoxib (n = 20; 29.4%), and simvastatin (n = 8; 11.8%). There was only one study that tested cardiac glycosides and none that studied ACE inhibitors. The most common tumor types were non-small-cell lung cancer (n = 19; 27.9%); breast (n = 8; 20.6%), colorectal (n = 7; 10.3%), and hepatocellular (n = 6; 8.8%). Most studies were conducted in a phase II trial (n = 38; 55.9%). Most studies were tested in metastatic cancers (n = 49; 72.1%) and in the first-line setting (n = 36; 521.9%). Four studies (5.9%) were stopped early because of difficulty with accrual. The majority of studies did not demonstrate an improvement in either progression-free survival (86.1% of studies testing progression-free survival) or in overall survival (94.3% of studies testing overall survival). Progression-free survival was improved in five studies (7.4%), and overall survival was improved in three studies (4.4%). Overall survival was significantly worse in two studies (3.8% of studies testing overall survival), and progression-free survival was worse in one study (2.8% of studies testing progression-free survival).
CONCLUSIONS: Despite promising pre-clinical and population-based data, cardiovascular drugs and anti-inflammatory medications have overall not demonstrated benefit in the treatment or preventing recurrence of cancer. These findings may help guide future potential clinical trials involving these medications when applied in oncology.
METHODS: We performed a systematic literature review using PubMed and Web of Science with search terms including \"aspirin,\" \"NSAID,\" \"statin\" (including specific statin drug names), \"metformin,\" \"ACE inhibitors,\" and \"ARBs\" (including specific anti-hypertensive drug names) in combination with \"cancer.\" Searches were limited to human studies published between 2000 and 2023.
METHODS: The number and percentage of studies reported positive results and pooled estimates of overall survival, progression-free survival, response, and disease-free survival.
RESULTS: We reviewed 3094 titles and included 67 randomized clinical trials. The most common drugs that were tested were metformin (n = 21; 30.9%), celecoxib (n = 20; 29.4%), and simvastatin (n = 8; 11.8%). There was only one study that tested cardiac glycosides and none that studied ACE inhibitors. The most common tumor types were non-small-cell lung cancer (n = 19; 27.9%); breast (n = 8; 20.6%), colorectal (n = 7; 10.3%), and hepatocellular (n = 6; 8.8%). Most studies were conducted in a phase II trial (n = 38; 55.9%). Most studies were tested in metastatic cancers (n = 49; 72.1%) and in the first-line setting (n = 36; 521.9%). Four studies (5.9%) were stopped early because of difficulty with accrual. The majority of studies did not demonstrate an improvement in either progression-free survival (86.1% of studies testing progression-free survival) or in overall survival (94.3% of studies testing overall survival). Progression-free survival was improved in five studies (7.4%), and overall survival was improved in three studies (4.4%). Overall survival was significantly worse in two studies (3.8% of studies testing overall survival), and progression-free survival was worse in one study (2.8% of studies testing progression-free survival).
CONCLUSIONS: Despite promising pre-clinical and population-based data, cardiovascular drugs and anti-inflammatory medications have overall not demonstrated benefit in the treatment or preventing recurrence of cancer. These findings may help guide future potential clinical trials involving these medications when applied in oncology.
摘要：
背景：由于令人鼓舞的临床前数据和支持性观察研究，人们对应用心血管药物(包括阿司匹林，血管紧张素转换酶[ACE]抑制剂，他汀类药物，和二甲双胍）被批准用于治疗高血压等疾病，高脂血症,和糖尿病进入肿瘤学领域。此外，考虑到癌症治疗的成本越来越高，这些药物为治疗或预防癌症复发提供了可能更实惠的途径.我们试图研究从心脏病学或抗炎药重新利用的药物治疗癌症的抗癌作用。我们特别评估了以下药物类别：HMG-CoA还原酶抑制剂（他汀类药物），环加氧酶抑制剂，阿司匹林,二甲双胍,血管紧张素受体阻滞剂（ARB）和血管紧张素转换酶抑制剂。我们还包括非甾体抗炎药（NSAIDs），因为它们通过阻断前列腺素和减少炎症而发挥与阿司匹林相似的机制，这被认为是促进癌症发展的。
方法：我们使用PubMed和WebofScience进行了系统的文献综述，检索词包括“阿司匹林，\"\"NSAID,\"\"他汀\"（包括特定的他汀类药物名称），“二甲双胍，“”ACE抑制剂，“和”ARBs“（包括特定的抗高血压药物名称）与”癌症的组合。搜索仅限于2000年至2023年之间发表的人类研究。
方法：报告阳性结果的研究数量和百分比以及总生存期的汇总估计，无进展生存期,回应,和无病生存。
结果：我们回顾了3094篇论文，纳入了67项随机临床试验。最常见的药物是二甲双胍（n=21；30.9%）。塞来昔布（n=20；29.4%），和辛伐他汀(n=8;11.8%)。只有一项研究测试了强心苷，没有一项研究了ACE抑制剂。最常见的肿瘤类型为非小细胞肺癌（n=19；27.9%）；乳腺癌（n=8；20.6%）。结直肠(n=7；10.3%)，和肝细胞（n=6;8.8％）。大多数研究是在II期试验中进行的（n=38；55.9％）。大多数研究在转移性癌症（n=49;72.1％）和一线背景（n=36;521.9％）中进行了测试。四项研究(5.9%)因应计困难而提前停止。大多数研究没有证明无进展生存期（86.1%的研究测试无进展生存期）或总生存期（94.3%的研究测试总生存期）有改善。5项研究的无进展生存率得到改善（7.4%），3项研究的总生存率提高(4.4%).两项研究的总生存率明显更差（3.8%的研究检测总生存率），一项研究的无进展生存期较差(2.8%的无进展生存期研究).
结论：尽管有希望的临床前和基于人群的数据，心血管药物和抗炎药在治疗或预防癌症复发方面总体上没有显示出益处.这些发现可能有助于指导涉及这些药物应用于肿瘤学的未来潜在临床试验。
方法：我们使用PubMed和WebofScience进行了系统的文献综述，检索词包括“阿司匹林，\"\"NSAID,\"\"他汀\"（包括特定的他汀类药物名称），“二甲双胍，“”ACE抑制剂，“和”ARBs“（包括特定的抗高血压药物名称）与”癌症的组合。搜索仅限于2000年至2023年之间发表的人类研究。
方法：报告阳性结果的研究数量和百分比以及总生存期的汇总估计，无进展生存期,回应,和无病生存。
结果：我们回顾了3094篇论文，纳入了67项随机临床试验。最常见的药物是二甲双胍（n=21；30.9%）。塞来昔布（n=20；29.4%），和辛伐他汀(n=8;11.8%)。只有一项研究测试了强心苷，没有一项研究了ACE抑制剂。最常见的肿瘤类型为非小细胞肺癌（n=19；27.9%）；乳腺癌（n=8；20.6%）。结直肠(n=7；10.3%)，和肝细胞（n=6;8.8％）。大多数研究是在II期试验中进行的（n=38；55.9％）。大多数研究在转移性癌症（n=49;72.1％）和一线背景（n=36;521.9％）中进行了测试。四项研究(5.9%)因应计困难而提前停止。大多数研究没有证明无进展生存期（86.1%的研究测试无进展生存期）或总生存期（94.3%的研究测试总生存期）有改善。5项研究的无进展生存率得到改善（7.4%），3项研究的总生存率提高(4.4%).两项研究的总生存率明显更差（3.8%的研究检测总生存率），一项研究的无进展生存期较差(2.8%的无进展生存期研究).
结论：尽管有希望的临床前和基于人群的数据，心血管药物和抗炎药在治疗或预防癌症复发方面总体上没有显示出益处.这些发现可能有助于指导涉及这些药物应用于肿瘤学的未来潜在临床试验。
