Therapeutic potential of anamorelin, a novel, oral ghrelin mimetic, in patients with cancer-related cachexia: a multicenter, randomized, double-blind, crossover, pilot study
Therapeutic potential of anamorelin, a novel, oral ghrelin mimetic, in patients with cancer-related cachexia: a multicenter, randomized, double-blind, crossover, pilot study
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DOI：
10.1007/s00520-012-1500-1
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发表时间：
2013-01-01
影响因子：
3.1
通讯作者：
Allen, Suzan
中科院分区：
文献类型：
--
作者：
Garcia, Jose M.;Friend, John;Allen, Suzan
癌症中的恶病质会对患者的症状感知、健康状况和治疗反应产生不利影响，并缩短生存期。阿拉莫林是生长素释放肽的口服模拟物，已被证明可以增加健康志愿者的体重和合成代谢激素水平，并且正在研究用于治疗癌症恶病质。这项多中心、双盲、安慰剂对照、交叉研究评估了阿拉莫林对 16 名患有不同癌症和恶病质的患者的作用。患者被随机分配至阿拉莫林 50 毫克/天或安慰剂组，为期 3 天。随后进行 3 至 7 天的清除期，然后更换治疗方法。评估包括体重、食欲、食物摄入量、生长激素 (GH) 水平、患者报告的症状评估（例如安德森症状评估量表 [ASAS] 和纳入标准）和安全性。与安慰剂相比，Anamorelin 显着增加了体重（0.77 kg 对比 -0.33 kg）。与安慰剂相比，食物摄入量有所增加，但并不显着。 GH 在所有时间点（给药后 0.5-4 小时）均显着增加。与安慰剂组的-3.56 ng/mL相比，阿拉莫林治疗组的胰岛素样生长因子-1 (IGF-1)显着增加了54.09 ng/mL；胰岛素样生长因子结合蛋白3 (IGFBP-3) 的显着变化分别为0.75 μg/mL 和-0.19 μg/mL。患者报告的症状，包括通过 ASAS 测量的食欲，在服用阿拉莫林后显着改善（8.1 vs. 安慰剂 1.0）。四名患者的不良事件（AE）可能或很可能与阿拉莫林相关：高血糖（两名患者）、恶心（一名患者）和头晕（一名患者）。大多数不良事件都是轻微的；没有患者因 AE 而退出。Anamorelin 在癌症恶病质中表现出显着的代谢、临床和患者评价效果。进一步的研究是有必要的。
Cachexia in cancer adversely affects patients' perception of symptoms, well-being, and response to therapy, and shortens survival. Anamorelin, an oral mimetic of ghrelin, has been shown to increase body weight and anabolic hormone levels in healthy volunteers and is being investigated to treat cancer cachexia.This multicenter, double-blind, placebo-controlled, crossover study evaluated the effects of anamorelin in 16 patients with different cancers and cachexia. Patients were randomly assigned to anamorelin 50 mg/day or placebo for 3 days. A 3- to 7-day washout period followed and then treatments were switched. Assessments included body weight, appetite, food intake, growth hormone (GH) levels, patient-reported symptom assessments (e.g., the Anderson Symptom Assessment Scale [ASAS] and also an inclusion criterion), and safety.Anamorelin significantly increased body weight compared with placebo (0.77 kg vs. -0.33 kg). Food intake increased compared with placebo, but not significantly. GH significantly increased at all time points (0.5-4 h postdose). Insulin-like growth factor-1 (IGF-1) significantly increased by 54.09 ng/mL with anamorelin treatment compared with -3.56 ng/mL for placebo; significant changes in insulin-like growth factor-binding protein 3 (IGFBP-3) were 0.75 mu g/mL vs. -0.19 mu g/mL, respectively. Patient-reported symptoms, including appetite as measured by ASAS, significantly improved with anamorelin (8.1 vs. 1.0 for placebo). Adverse events (AEs) in four patients were possibly or probably related to anamorelin: hyperglycemia (two patients), nausea (one patient), and dizziness (one patient). Most AEs were mild; no patients withdrew due to AEs.Anamorelin showed significant metabolic, clinical, and patient-rated effects in cancer cachexia. Further studies are warranted.