BACKGROUND Lymphangioleiomyomatosis (LAM) is a rare, low-grade multisystem neoplastic disease. Most LAM patients are at a high risk of losing lung function at an accelerated rate and developing progressive dyspnea. Recently, several studies have reported their experience with pharmacological treatments for LAM. Therefore, we conducted a systematic review and meta-analysis to assess the efficacy and safety of these therapies. METHODS PubMed (Medline), EMBASE, Cochrane Library, Web of Science and EBSCO Host were searched (until March 31, 2019) for eligible prospective studies regarding LAM patients treated with pharmacological treatments. Random effect models were used for quantitative analysis. RESULTS Fourteen prospective studies regarding five pharmacological treatments (including sirolimus, everolimus, doxycycline, triptorelin, and a combination therapy of sirolimus and hydroxychloroquine) were enrolled in our systematic review, and ten of them were used for the meta-analysis. Seven prospective studies reported that sirolimus was effective at improving or stabilizing lung function and alleviating renal angiomyolipoma (AML) in LAM patients. Subsequent quantitative analyses showed that during sirolimus treatment, the pooled values of lung function and 6-min walk distance (6MWD) were not significantly changed (P > 0.05), with the pooled response rate of AML being 0.62 (95% confidence intervals [CIs]: 0.43 to 0.82, I2 = 65%). Regarding everolimus, three prospective studies reported similar effects to those of sirolimus with regard to preserving lung function and reducing AMLs. The meta-analysis showed that the changes in lung function during everolimus treatment were not statistically significant (P > 0.05), while the pooled response rate of AML was 0.78 (95% CI: 0.68 to 0.88, I2 = 8%). Neither the qualitative nor the quantitative results confirmed the benefits of doxycycline or triptorelin treatment, and the effects of the combination therapy were unclear in LAM patients. Most of the adverse events during pharmacological treatments were low or moderate grade and tolerable. CONCLUSIONS Overall, sirolimus and everolimus were recommended for the treatment of LAM because they could stabilize lung function and alleviate renal AML. Doxycycline and triptorelin were not recommended for the treatment of LAM because no beneficial outcomes were consistently observed. The efficacy and safety of combination therapy remain to be further explored.

中文翻译：

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淋巴管平滑肌瘤病的药物治疗的有效性和安全性。

背景技术淋巴管平滑肌肌瘤病（LAM）是一种罕见的低度多系统肿瘤性疾病。大多数LAM患者极有可能以加速的速度丧失肺功能并发展为进行性呼吸困难。最近，一些研究报告了他们在LAM药物治疗方面的经验。因此，我们进行了系统的综述和荟萃分析，以评估这些疗法的疗效和安全性。方法（截至2019年3月31日）在PubMed（Medline），EMBASE，Cochrane图书馆，Web of Science和EBSCO Host中进行检索，以寻找有关接受过药理治疗的LAM患者的合格前瞻性研究。随机效应模型用于定量分析。结果十四项前瞻性研究涉及五种药物治疗（包括西罗莫司，依维莫司，强力霉素，曲普瑞林，以及西罗莫司和羟氯喹的联合疗法）纳入我们的系统评价，其中十种用于荟萃分析。七项前瞻性研究报告说，西罗莫司可有效改善或稳定LAM患者的肺功能并减轻肾血管平滑肌脂肪瘤（AML）。随后的定量分析表明，在西罗莫司治疗期间，肺功能和6分钟步行距离（6MWD）的合并值没有显着变化（P> 0.05），合并的AML反应率为0.62（95％置信区间[CIs] ]：0.43至0.82，I2 = 65％）。关于依维莫司，三项前瞻性研究报告了在维持肺功能和减少AML方面与西罗莫司相似的作用。荟萃分析显示，依维莫司治疗期间肺功能的变化无统计学意义（P> 0.05），而AML合并应答率为0.78（95％CI：0.68至0.88，I2 = 8％）。定性和定量结果均未证实强力霉素或曲普瑞林治疗的益处，并且在LAM患者中联合治疗的效果尚不清楚。药物治疗期间的大多数不良事件均为低度或中度等级且可以耐受。结论总体而言，西罗莫司和依维莫司被推荐用于治疗LAM，因为它们可以稳定肺功能并减轻肾脏AML。不推荐使用强力霉素和曲普瑞林治疗LAM，因为未始终观察到有益的结果。