Shameem Raji, Lacouture Mario, Wu Shenhong
Department of Internal Medicine, Lenox Hill Hospital , New York, New York , USA.
Acta Oncol. 2015 Jan;54(1):124-32. doi: 10.3109/0284186X.2014.923583. Epub 2014 Jun 10.
Inhibitors of the mammalian target of rapamycin (mTOR) are currently approved for the treatment of several cancers, and their use is associated with serious rash, which affects patient's quality of life and leads to undesirable dose reductions or interruptions. A meta-analysis of randomized controlled trials (RCTs) was performed to determine the overall risk of developing high-grade rash with mTOR inhibitors in cancer patients.
We searched the PubMed database and abstracts presented at the American Society of Clinical Oncology (ASCO) meetings up to December 2013 for relevant studies. Eligible studies included RCTs in which everolimus or temsirolimus was compared to controls in cancer patients. The summary incidence, relative risk (RR), and 95% confidence intervals (CI) were calculated using a random- or fixed-effects model depending on the heterogeneity of the included trials.
A total of 11 RCTs with 4752 patients (mTORs: 2725, controls: 2027) with a variety of solid tumors were included in the analysis. The incidences of all-grade (grade 1-4) and high-grade rash (grade 3-4) were 27.3% (95% CI 21.0-34.7%) and 1.0% (95% CI 0.6-1.4%), respectively. In comparison with controls, mTOR inhibitors significantly increased the risk for developing all-grade rash (RR = 3.55, 95% CI 3.0-4.20, p < 0.001) and high-grade rash (RR = 4.25, 95% CI 1.63-11.10, p = 0.003). The increased risk of high-grade rash did not vary significantly among different tumors (p = 0.91). There was no significant difference between everolimus and temsirolimus (p = 0.60). There was also no significant difference between mTOR inhibitors alone and in combination with other agents (p = 0.57).
Everolimus and temsirolimus significantly increased the risk of high-grade rash in cancer patients. Early recognition and appropriate treatment is recommended.
哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂目前已被批准用于治疗多种癌症，但其使用与严重皮疹相关，这会影响患者的生活质量，并导致不必要的剂量减少或治疗中断。我们进行了一项随机对照试验（RCT）的荟萃分析，以确定癌症患者使用mTOR抑制剂出现重度皮疹的总体风险。
我们检索了截至2013年12月的PubMed数据库以及在美国临床肿瘤学会（ASCO）会议上发表的摘要，以查找相关研究。符合条件的研究包括将依维莫司或替西罗莫司与癌症患者对照组进行比较的随机对照试验。根据纳入试验的异质性，使用随机效应模型或固定效应模型计算汇总发病率、相对风险（RR）和95%置信区间（CI）。
分析共纳入了11项随机对照试验，涉及4752例患有各种实体瘤的患者（mTOR抑制剂组：2725例，对照组：2027例）。所有级别（1 - 4级）和重度皮疹（3 - 4级）的发生率分别为27.3%（95%CI 21.0 - 34.7%）和1.0%（95%CI 0.6 - 1.4%）。与对照组相比，mTOR抑制剂显著增加了出现所有级别皮疹的风险（RR = 3.55，95%CI 3.0 - 4.20，p < 0.001）和重度皮疹的风险（RR = 4.25，95%CI 1.63 - 11.10，p = 0.003）。重度皮疹风险的增加在不同肿瘤之间无显著差异（p = 0.91）。依维莫司和替西罗莫司之间无显著差异（p = 0.60）。mTOR抑制剂单独使用与联合其他药物使用之间也无显著差异（p = 0.57）。
依维莫司和替西罗莫司显著增加了癌症患者出现重度皮疹的风险。建议早期识别并进行适当治疗。
