Shohdy Kyrillus S, Lasheen Shaimaa, Kassem Loay, Abdel-Rahman Omar
Clinical Oncology Department, Kasr Alainy School of Medicine, Cairo University, Al-Saray St. El-Maniel, 11451, Cairo, Egypt.
Clinical Oncology Department, Kasr Alainy School of Medicine, Cairo University, Cairo, Egypt.
Ther Adv Drug Saf. 2017 Nov;8(11):337-347. doi: 10.1177/2042098617722516. Epub 2017 Aug 8.
Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors show promising results in metastatic breast cancer. However, an increased incidence of adverse events is remarkable. Among others, gastrointestinal (GI) involvement is of momentous impact on patients and their quality of life.
Our search included and databases. Randomized phase II/III trials in metastatic breast cancer receiving CDK4/6 inhibitors were identified and considered relevant based on providing a sufficient safety profile on the incidence of adverse GI effects.
Of the 999 records initially screened for relevance, 33 articles were found relevant and 4 studies were finally eligible for meta-analysis with a total of 2007 patients. The relative risk (RR) for all-grade nausea was 1.48 [95% confidence interval (CI): 1.12-1.93, = 0.005], vomiting was 1.74 (95% CI: 1.09-2.76, = 0.02), decreased appetite was 1.42 (95% CI: 1.07-1.88, = 0.02), and for diarrhea it was 1.44 (95% CI: 1.19-1.74, = 0.0002). Meanwhile, the RR for high-grade nausea was 1.10 (95% CI: 0.29-4.13, = 0.89), vomiting was 1.38 (95% CI: 0.25-7.75, = 0.72), decreased appetite was 4.00 (95% CI: 0.87-18.37, = 0.07), and high-grade diarrhea was 1.19 (95% CI: 0.44-3.21, = 0.73).
Selective CDK4/6 inhibitors were not associated with higher-grade GI toxicities reflecting a well-tolerated safety profile. Regarding the increase in all-grade GI toxicities, it needs further caution with addition of cytotoxic chemotherapy.
细胞周期蛋白依赖性激酶4和6（CDK4/6）抑制剂在转移性乳腺癌中显示出有前景的结果。然而，不良事件的发生率增加显著。其中，胃肠道（GI）受累对患者及其生活质量有重大影响。
我们的检索包括[具体数据库1]和[具体数据库2]数据库。确定了接受CDK4/6抑制剂的转移性乳腺癌的随机II/III期试验，并基于提供关于不良胃肠道影响发生率的充分安全性概况而被认为相关。
在最初筛选相关性的999条记录中，发现33篇文章相关，4项研究最终符合荟萃分析条件，共2007例患者。所有级别的恶心的相对风险（RR）为1.48[95%置信区间（CI）：1.12 - 1.93，P = 0.005]，呕吐为1.74（95% CI：1.09 - 2.76，P = 0.02），食欲减退为1.42（95% CI：1.07 - 1.88，P = 0.02），腹泻为1.44（95% CI：1.19 - 1.74，P = 0.0002）。同时，高级别恶心的RR为1.10（95% CI：0.29 - 4.13，P = 0.89），呕吐为1.38（95% CI：0.25 - 7.75，P = 0.72），食欲减退为4.00（95% CI：0.87 - 18.37，P = 0.07），高级别腹泻为1.19（95% CI：0.44 - 3.21，P = 0.73）。
选择性CDK4/6抑制剂与反映良好耐受性安全性概况的更高级别胃肠道毒性无关。关于所有级别的胃肠道毒性增加，在添加细胞毒性化疗时需要进一步谨慎。
