Thambamroong Tawasapon, Seetalarom Kasan, Saichaemchan Siriwimon, Pumsutas Yanisa, Prasongsook Naiyarat
Division of Medical Oncology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.
Division of Clinical Nutrition, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.
J Nutr Metab. 2022 Jun 2;2022:5425619. doi: 10.1155/2022/5425619. eCollection 2022.
Cancer anorexia-cachexia syndrome (CAS) is a significant comorbidity among all patients with cancer, increasing the mortality rate. Almost all patients with head and neck cancer experience this syndrome. CAS causes increased energy expenditure by increasing systemic inflammation and decreasing energy consumption due to anorexia. It leads to skeleton muscle breakdown and reduces the quality of life. Nutritional interventions and primary cancer treatment are the mainstays to manage this situation. However, a vicious cycle causes CAS to persist, especially in head and neck cancer, where tumour location and its treatment interfere with nutritional interventions. Curcumin shows anti-inflammatory effects, including modulated CAS in animal and in vitro studies.
The study aimed to determine the effect of curcumin to treat cancer anorexia-cachexia syndrome among current patients with locally advanced or advanced head and neck cancer.
This constitutes a randomised, double-blind, placebo-controlled phase IIa study. Twenty patients with CAS in locally advanced or advanced head and neck cancer adequately nourished via a feeding tube were enrolled and randomised in a 1 : 1 ratio to receive oral curcumin (at a dose of 4000 mg daily) ( = 10) or placebo ( = 10) for 8 weeks. The primary endpoint was body composition (muscle mass, body fat mass, and basal metabolic rate). The secondary endpoints were handgrip muscle strength, body mass index, absolute lymphocyte count, and safety and toxicity.
There was a statistically significant benefit from curcumin on improving muscle mass compared with placebo (2.16% [95% confidence interval; CI, -0.75 to 5.07] vs. -3.82% [95% CI, -8.2 to 0.57]; =0.019). The other parameters of body composition were not significant but tended to favour curcumin benefit. The body fat mass (-0.51 [95% CI, -21.89 to 20.86] vs. -8.97% [95% CI, -19.43 to 1.49]; =0.432) and percentage of mean change in the basal metabolic rate were noted (BMR) (0.54% [95% CI, -1.6 to 2.67] vs. -1.61% [95% CI, -4.05 to 0.84]; =0.153). Notably, patients treated with curcumin exhibited less reduction in handgrip muscle strength and absolute lymphocyte count but was not significant. Similarly, most adverse events were grade 1 in both groups.
The curcumin add-on resulted in a significant increase in muscle mass than standard nutritional support. Furthermore, it may improve and delay a decrease in the other body composition parameters, handgrip strength, and absolute lymphocyte count. Curcumin was safe and well tolerated. This constitutes an unmet need for clinical trials. This trial is registered with NCT04208334.
癌症恶病质综合征（CAS）是所有癌症患者中一种重要的合并症，会增加死亡率。几乎所有头颈癌患者都会出现这种综合征。CAS通过增加全身炎症反应和因厌食导致能量消耗减少，从而使能量消耗增加。它会导致骨骼肌分解，降低生活质量。营养干预和原发性癌症治疗是应对这种情况的主要手段。然而，一个恶性循环导致CAS持续存在，尤其是在头颈癌中，肿瘤位置及其治疗会干扰营养干预。姜黄素在动物和体外研究中显示出抗炎作用，包括对CAS的调节作用。
本研究旨在确定姜黄素对当前局部晚期或晚期头颈癌患者治疗癌症恶病质综合征的效果。
这是一项随机、双盲、安慰剂对照的IIa期研究。纳入20例通过饲管充分营养的局部晚期或晚期头颈癌且患有CAS的患者，按1∶1比例随机分组，接受口服姜黄素（每日剂量4000毫克）（n = 10）或安慰剂（n = 10）治疗8周。主要终点是身体成分（肌肉量、体脂肪量和基础代谢率）。次要终点是握力肌肉力量、体重指数、绝对淋巴细胞计数以及安全性和毒性。
与安慰剂相比，姜黄素在改善肌肉量方面有统计学显著益处（2.16%[95%置信区间；CI，-0.75至5.07]对-3.82%[95%CI，-8.2至0.57]；P = 0.019）。身体成分的其他参数虽无显著差异，但倾向于显示姜黄素有益。体脂肪量（-0.51[95%CI，-21.89至20.86]对-8.97%[95%CI，-19.43至1.49]；P = 0.432）以及基础代谢率（BMR）的平均变化百分比也有记录（0.54%[95%CI，-1.6至2.67]对-1.61%[95%CI，-4.05至0.84]；P = 0.153）。值得注意的是，接受姜黄素治疗的患者握力肌肉力量和绝对淋巴细胞计数的下降较少，但不显著。同样，两组中大多数不良事件为1级。
添加姜黄素比标准营养支持能显著增加肌肉量。此外，它可能改善并延缓其他身体成分参数、握力和绝对淋巴细胞计数的下降。姜黄素安全且耐受性良好。这构成了一项临床试验中未满足的需求。本试验已在ClinicalTrials.gov注册，注册号为NCT04208334。
