Acute-phase response proteins are related to cachexia and accelerated angiogenesis in gastroesophageal cancers.

BACKGROUND: Accurate outcome prediction in gastroesophageal malignancies is challenging. Acute-phase response proteins (APRPs) have been claimed to be independent prognosticators, although the basis for their association with prognosis remains unexplained. We hypothesized that, similarly to pancreatic and lung cancers, changes in APRPs in gastroesophageal malignancies are associated with cachexia and accelerated angiogenesis. METHODS: C-reactive protein (CRP), albumin and transferrin serum levels were evaluated and the Glasgow Prognostic Score (GPS) calculated. These data were compared with concentrations of circulating interleukin (IL)-1, IL-6 and IL-8, tumor necrosis factor-alpha (TNF-alpha), vascular endothelial growth factor (VEGF)-A, VEGF-C and midkine in 96 gastroesophageal cancer patients (49 with cachexia) and 42 healthy subjects. Results: Albumin and CRP levels were altered in the cancer patients, with further CRP elevation in those with cachexia. Transferrin was decreased only in the cachectic patients. The interrelationships between the APRPs were strengthened in cachexia and only then were APRPs correlated with the cytokines elevated in gastroesophageal cancer-related cachexia: IL-6, IL-8, VEGF-A and midkine. GPS corresponded well to transferrin, IL-1, IL-6, IL-8, TNF-alpha, VEGF-A and midkine concentrations. CONCLUSIONS: Cachexia in gastroesophageal cancers is associated with changes in APRP concentrations. This, together with a direct relationship of APRPs with accelerated angiogenesis, may constitute a foundation for the association of APRPs and GPS with outcome in these malignancies.     

细胞因子IL-1、IL-6和IL-8水平与胃窦癌恶病质关系

目的探讨胃窦癌病人血清细胞因子白细胞介素（IL）-1、IL-6和IL-8的水平与恶病质发生的关系。方法125例胃窦癌病人分为恶病质组与非恶病质组,将近6个月体质量下降〉10％者定义为恶病质病人。通过放射免疫学方法对胃窦癌病人及健康对照组进行血清IL-1、IL-6和IL-8含量的检测。结果胃窦癌病人血清中3种细胞因子含量较对照组均显著升高（Z=-8．186～-4．665,P〈0．05）,胃窦癌恶病质病人血清IL-6和IL-8含量较非恶病质病人显著升高（Z=-5．018、-3．134,P〈0．05）。多因素Logistic回归分析显示,IL-6（OR=1．048,95％CI：1．021～1．075）和IL-8（OR=3．150,95％CI：0．988～10．037）为恶病质发生的高风险性因素。结论血清IL-6和IL-8水平与胃窦癌病人恶病质的发生具有相关性。     

Anti-cytokine strategies for the treatment of cancer-related anorexia and cachexia

Importance of the field: Cachexia is a syndrome characterized by body weight loss and metabolic abnormalities. It is a frequent feature of patients affected by chronic pathologies, including cancer. Neoplastic patients with cachexia show increased morbidity and mortality rates, benefit less from antineoplastic therapies, and have a poorer quality of life. Among the general mechanisms proposed to account for cachexia, anorexia and altered homeostasis of hormones and cytokines appear to play a major role.

Areas covered in this review: The present review will focus on anti-inflammatory drugs useful for the treatment of cancer-related anorexia and cachexia.

What the reader will gain: Molecules able to block cytokine production or biological activity are currently under evaluation. At present, none of them has been authorized for the clinical treatment of cancer-related anorexia and cachexia, since the few published clinical trials lead to contrasting results, and others are still pending.

Take home message: Considering the multifactorial pathogenesis of cancer-related anorexia and cachexia, combination protocols are probably the better choice. In this regard, anti-cytokine strategies should be pursued and included in the treatment of neoplastic patients, although cytokines modulate a number of processes.     

Nerve growth factor links oral cancer progression, pain, and cachexia

Cancers often cause excruciating pain and rapid weight loss, severely reducing quality of life in cancer patients. Cancer-induced pain and cachexia are often studied and treated independently, although both symptoms are strongly linked with chronic inflammation and sustained production of proinflammatory cytokines. Because nerve growth factor (NGF) plays a cardinal role in inflammation and pain, and because it interacts with multiple proinflammatory cytokines, we hypothesized that NGF acts as a key endogenous molecule involved in the orchestration of cancer-related inflammation. NGF might be a molecule common to the mechanisms responsible for clinically distinctive cancer symptoms such as pain and cachexia as well as cancer progression. Here we reported that NGF was highly elevated in human oral squamous cell carcinoma tumors and cell cultures. Using two validated mouse cancer models, we further showed that NGF blockade decreased tumor proliferation, nociception, and weight loss by orchestrating proinflammatory cytokines and leptin production. NGF blockade also decreased expression levels of nociceptive receptors TRPV1, TRPA1, and PAR-2. Together, these results identified NGF as a common link among proliferation, pain, and cachexia in oral cancer. Anti-NGF could be an important mechanism-based therapy for oral cancer and its related symptoms.     

急性移植物抗宿主病病人血清IL-2、IL-8、IL-10及TNF-α水平变化的研究

为了探讨细胞因子IL-2、TNF—α、IL-10、IL-8在异基因造血干细胞移植后aGVHD发病中的作用，观察33例Allo-HSCT患者aGVHD的发病情况。aGVHD的诊断主要依据临床表现，部分病例还依据皮肤、肠粘膜活检的病理学变化。移植前后定期采集患者血清，采用放射免疫法检测细胞因子IL-2、TNF—α、IL-10、IL-8的浓度的变化。结果发现，异基因造血干细胞移植后33例患者均获得造血功能重建，13例发生aGVHD，其中8例Ⅰ度aGVHD，5例Ⅱ-Ⅳ度aGVHD。IL-2、TNF—α水平在aGVHD阳性组明显高于aGVHD阴性组，而IL-10的水平在aGVHD阳性组明显低于aGVHD阴性组，IL-8水平的变化无统计学意义。结论：细胞因子IL-2、TNF—α在临床aGVHD的发病中起重要的正向调节作用，定期检测患者血清的IL-2、TNF—α水平有助于预测aGVHD的发生。     

Suramin interferes with interleukin-6 receptor binding in vitro and inhibits colon-26-mediated experimental cancer cachexia in vivo.

Neoplastic diseases are frequently associated with metabolic changes collectively known as cancer cachexia. The presence of cachexia complicates therapeutic intervention and is an important cause of death in cancer patients. At present there is no effective treatment for cachexia. Recently, the involvement of interleukin-6 (IL-6) in the wasting of colon-26 adenocarcinoma-bearing mice was demonstrated. The research presented here establishes an anticachectic role for the experimental drug suramin, since it partially blocks (up to 60%) the catabolic effects associated with the growth of this tumor in vivo. Suramin prevents the binding of IL-6 to its cell surface receptor subunits, as demonstrated by radioreceptor binding assay and affinity crosslinking experiments. Furthermore, the uptake of radioactive IL-6 by the liver is significantly reduced in suramin-treated mice. On the other hand, the drug is approximately 10-fold less potent in inhibiting the binding of tumor necrosis factor-alpha to indicator cell line in vitro and fails to block liver uptake of this cytokine in vivo. Collectively, these results suggest that suramin inhibits cancer-associated wasting, in part by interfering with the binding of IL-6 to its receptor. Whether suramin inhibits the action of other factors/cytokines that may also participate in colon-26-mediated cachexia is not yet known.     

Tumor-derived IL-6 and trans-signaling among tumor,fat, and muscle mediate pancreatic cancer cachexia

Most patients with pancreatic adenocarcinoma (PDAC) suffer cachexia; some do not. To model heterogeneity, we used patient-derived orthotopic xenografts. These phenocopied donor weight loss. Furthermore, muscle wasting correlated with mortality and murine IL-6, and human IL-6 associated with the greatest murine cachexia. In cell culture and mice, PDAC cells elicited adipocyte IL-6 expression and IL-6 plus IL-6 receptor (IL6R) in myocytes and blood. PDAC induced adipocyte lipolysis and muscle steatosis, dysmetabolism, and wasting. Depletion of IL-6 from malignant cells halved adipose wasting and abolished myosteatosis, dysmetabolism, and atrophy. In culture, adipocyte lipolysis required soluble (s)IL6R, while IL-6, sIL6R, or palmitate induced myotube atrophy. PDAC cells activated adipocytes to induce myotube wasting and activated myotubes to induce adipocyte lipolysis. Thus, PDAC cachexia results from tissue crosstalk via a feed-forward, IL-6 trans-signaling loop. Malignant cells signal via IL-6 to muscle and fat, muscle to fat via sIL6R, and fat to muscle via lipids and IL-6, all targetable mechanisms for treatment of cachexia.     

血清中IL-6和IL-8测定在食管癌放疗患者预后中的临床价值

目的寻找食管癌放疗预后血清学指标。方法120例食管癌患者作为研究组,食管良性患者40例,健康体检者40例作为对照组。采用酶联免疫吸附（ELISA）法检测研究组以及对照组血清中IL-6和IL．8。结果①良性患者组血清IL-6（tIL-6=3．677。P〈O．05）,IL-8（tIL-8=5．963,P〈0．05）水平明显高于对照组;食管癌组血清IL-6（tIL-6=12．813,P〈0．05）,IL-8（tIL-8=4．938,P〈O．05）水平明显高于良性患者组。②食管癌I期血清IL-6水平为54．28±10．59pg／ml,IL-8水平为67．58±12．53pg／ml;Ⅱ期血清IL-6水平为67．42±10．27pg／ml,IL-8水平为78．57±11．84pg／ml;Ⅲ期血清IL6水平为81．37±10．18pg／ml,IL-8水平为92．24±8．9pg／ml。食管癌Ⅱ期血清IL-6（tIL-6=5．814,P〈0．05）,IL-8（tIL-8=4．163,P〈0．05）水平明显高于I期;Ⅲ期IL-6（tIL-6=6．099,P〈O．05）,IL-8（tIL-8=5．672,P〈O．05）水平明显高于Ⅱ期。③120例食管癌患者经放射治疗后38例复发或转移。食管癌患者复发或转移组血清IL-6水平为97．78±11．94pg／ml,IL-8水平为122．28±12．57pg／ml,稳定组血清IL-6水平为66．46±10．42pg／ml,IL-8水平为87．37±11．32pg／ml;食管癌患者复发或转移组血清IL-6（tIL-6=14．622,P〈0．05）,IL-8（tIL-8=15．178,P〈0．05）水平明显高于稳定组。结论1L-6和IL-8可能参与了食管癌发生、发展的全过程。它的变化可间接反映食管癌的生物学行为和预后,对其监测具有重要的临床意义。     

有氧运动训练对大鼠下丘脑、垂体IL-1βmRNA、IL-6mRNA的影响

目的：研究长时间运动对老年机体下丘脑、垂体IL-1、IL-6的基因表达的影响。方法：将大鼠随机分为3组：青年安静组（A组）、老年安静对照组（B组）、老年运动训练组（C组）,运动组大鼠在水中进行90d渐进游泳训练,采用PT-PCR的方法检测各组大鼠下丘脑、垂体IL-1、IL-6的基因表达。结果：在下丘脑老年大鼠与青年鼠相比IL-1mRNA和IL-6mRNA表达量显著升高（P〈0.01）,在垂体水平老年大鼠IL-1βmRNA的水平明显高于青年大鼠（P〈0.01）,而IL-6mRNA变化不显著（P〉0.05）。通过3个月的游泳训练老年大鼠下丘脑IL-6mRNA、垂体IL-1βmRNA水平有所下降（P〈0.01）,下丘脑IL-1βmRNA、垂体IL-6mRNA的表达水平变化不显著（P〉0.05）。结论：随着老化机体脑组织中炎性细胞因子的基因表达水平明显升高,运动可以抑制老年大鼠下丘脑、垂体细胞因子的基因表达水平,降低老年期神经细胞对炎症的反应性,有利于下丘脑-垂体-肾上腺轴的正常作用。     

癌性贫血患者血清Hepcidin及炎症介质因子LPS和IL-6表达及其意义

目的研究Hepcidin在癌性贫血发生中的意义及其与炎症介质因子细菌脂多糖(LPS)和白细胞介素-6(IL-6)之间的关系。方法应用双抗夹心生物素-亲和素-酶联免疫吸附试验(ABC-ELISA)方法检测50例癌性贫血患者和140例无贫血癌症患者的血清Hepcidin和LPS和IL-6,并分析Hepcidin与贫血、与IL-6以及LPS之间的相关关系。结果 ①癌性贫血患者血清Hepcidin为51.99±32.56μg/L明显高于无贫血患者的36.63±31.99μg/L(P<0.01)。②癌性贫血患者血清LPS和IL-6分别为75.33±62.63μg/L和39.36±82.60ng/L,均高于无贫血患者的63.43±38.76μg/L和10.38±22.00ng/L(均为P<0.05)。③癌性贫血患者的Hepcidin与LPS呈明显的正相关关系(r=0.397,t=2.996,P<0.01);Hepcidin与IL-6也呈正相关关系(r=0.302,t=2.201,P<0.05)。④癌性贫血患者的Hepcidin、LPS和IL-6三者均与血红蛋白无相关关系。结论癌性贫血患者高表达Hepcidin、LPS和IL-6,Hepcidin与LPS和IL-6均呈正相关关系;它们在癌性贫血的发生发展过程中起重要的作用。     

Investigating the utility of serum cytokine measurements in a multi-institutional cancer anorexia/weight loss trial

Background Interleukin-1 beta (IL-1), tumor necrosis factor alpha (TNF), and interleukin-6 (IL-6) have been implicated in the cancer anorexia/weight loss syndrome. However, previous smaller studies have yielded conflicting results as to whether circulating, serum concentrations of these cytokines are in fact elevated. As the translational component of a large multi-institutional trial, this study assessed the clinical value of serum concentrations of these cytokines in patients with this syndrome.Methods Patients with incurable cancer with anorexia and/or weight loss were eligible. All underwent weekly weight measurements and appetite assessment for the first month and then monthly assessments thereafter. Serum was obtained at baseline and at 1 month, and all three cytokines were measured with the Immunolite assay.Results A total of 118 patients participated. At baseline, 99%, 54%, and 47% of patients samples had undetectable IL-1, TNF, and IL-6, respectively. Similar results were obtained at 1 month. No correlations were observed between serum cytokine concentrations and changes in weight or appetite. Baseline serum IL-6 predicted a diminished survival but only after adjustment for age and cancer site.Conclusion Serum concentrations of IL-1, TNF, and IL-6, as measured in this study, provide data of limited clinical value for patients with the cancer anorexia/weight loss syndrome.This study was conducted as a collaborative trial of the North Central Cancer Treatment Group and Mayo Clinic, and was supported in part by Public Health Service grants: CA-25224, CA-37404, CA-15083, CA-63826, CA- 63849, CA-35269, CA-35195, CA-35113, CA-60276, CA-52352, CA-35101, CA-35103, CA-63848, CA-35272, and CA-37417.     

Association of IL-1Ra gene polymorphism, but no association of IL-1beta and IL-4 gene polymorphisms, with Kawasaki disease

The purpose of this study was to evaluate whether IL-1 beta (IL-1beta promoter and IL-1beta exon 5), IL-1 receptor antagonist (IL-1 Ra), and IL-4 (IL-4 promoter and IL-4 intron 3) gene polymorphisms act as markers of susceptibility to Kawasaki disease (KD), or of the severity of the disease. The study included 107 KD patients and 103 normal controls. Polymorphisms for cytokine genes were detected by polymerase chain reaction (PCR). Genotypes and allelic frequencies for cytokine gene polymorphisms in both groups were compared. No significant difference was observed in the genotypes and allelic frequencies of cytokines between patients with coronary aneurysm and without. In addition, there was no significant association in the genotype and allelic frequencies of IL-1 beta, IL-4, and IL-6 in patients with KD. The genotype I/II for IL1-Ra and the frequency of allele II for IL1-Ra are associated with a higher susceptibility to KD, and thus may be useful markers for predicting the development of KD.     

新生儿缺氧缺血性脑病血清IL-6、IL-8的改变及临床意义

目的 研究新生儿缺氧缺血性脑病(HIE)患儿血清白细胞介素6(IL-6)、白细胞介素8(IL-8)的改变,探讨IL-6、IL-8水平与HIE和HIE病变程度之间的关系。方法 对47例患缺氧缺血性脑病的新生儿(中、重度组27例,轻度组20例)及同期五窒息、无重度感染的新生儿21例,分别于出生后3 d内及治疗10 d后采用ELISA法测定新生儿血清IL-6、IL-8水平。结果 各组间均存在显著性差异,缺氧缺血性脑病的新生儿血清IL-6、IL-8高于对照组,中、重度组高于轻度组。恢复期血清IL-6、IL-8明显降低。结论 新生儿HIE血清IL-6、IL-8水平变化与HIE和HIE病变严重程度有关,IL-6、IL-8在新生儿缺氧缺血性脑病的发病机理中起重要作用。     

Serum levels of leptin and proinflammatory cytokines in patients with gastrointestinal cancer

The aim was to investigate the serum levels of leptin, TNF-alpha, IL-1 beta, IL-6, insulin, and growth hormone in patients with upper gastrointestinal cancer and cachexia. A total of 39 patients with various advanced stage (stage IV) gastrointestinal malignancies were enrolled. These cancer patients were divided into two groups according to the presence or absence of cachexia. Fifteen healthy adults were recruited as the control group. Body mass index (BMI; kg/m2) was calculated. Serum leptin, tumour necrosis factor (TNF)-alpha interleukin (IL)-1 beta, interleukin (IL)-6, growth hormone, insulin, glucose, triglyceride, total protein, albumin, erythrocyte sedimentation rate, and CRP were measured. In both cancer groups (cachectic and non-cachectic) body mass index and serum leptin levels were lower than controls (p < 0.001). Serum IL-1 beta, IL-6, and growth hormone levels were higher in both cachectic and non-cachectic groups than those of controls (p < 0.05). Serum TNF-alpha level in non-cachectic group was also significantly higher than in control group (p < 0.01). There is no significant difference between three groups in terms of insulin resistance as assessed by HOMA index. Our results showed that some proinflammatory cytokine levels were increased and leptin level was decreased due to upper gastrointestinal cancers. Increased cytokine levels may lead to decreased food intake and caused a weight loss.     

The role of cytokines in cancer cachexia

A large number of observations point towards cytokines, polypeptides released mainly by immune cells, as the molecules responsible for the metabolic derangements associated with cancer-bearing states. Indeed, these alterations lead to a pathological state known as cancer cachexia which is, unfortunately, one of the worst effects of malignancy, accounting for nearly a third of cancer deaths. It is characterized by weight loss together with anorexia, weakness, anemia, and asthenia. The complications associated with the appearance of the cachectic syndrome affect both the physiological and biochemical balance of the patient and have effects on the efficiency of the anticancer treatment, resulting in a considerably decreased survival time. At the metabolic level, cachexia is associated with loss of skeletal muscle protein together with a depletion of body lipid stores. The cachectic patient, in addition to having practically no adipose tissue, is basically subject to an important muscle wastage manifested as an excessive nitrogen loss. The metabolic changes are partially mediated by alterations in circulating hormone concentrations (insulin, glucagon, and glucocorticoids in particular) or in their effectiveness. The present study reviews the involvement of different cytokines in the metabolic and physiological alterations associated with tumor burden and cachexia. Among these cytokines, some can be considered as procachectic (such as tumor necrosis factor-alpha), while others having opposite effects can be named as anticachectic cytokines. It is the balance between these two cytokine types that finally seems to have a key role in cancer cachexia.     

IL-23 and IL-27: new members of the growing family of IL-12-related cytokines with important implications for therapeutics

The recent discoveries of the two interleukin (IL)-12-related cytokines, IL-23 and IL-27, reveal that the regulation of cellular immunity is more complex than originally thought. Until these discoveries, the role of IL-12 in modulating cellular immune responses had been overestimated due to the belief that the IL-12 p40 subunit was unique to IL-12. However, because p40 is shared between IL-12 and IL-23, it would be expected that p40^-/- mice are doubly deficient in IL-12 and IL-23. Indeed, the essential role previously attributed to IL-12 in experimental autoimmune encephalitis during studies of p40^-/- mice has been shown to be due to IL-23 instead. The newest addition to the IL-12 cytokine family, IL-27, has unique features as well. Its specific action on naive CD4+ T cells in both mice and humans appears to distinguish it from the other IL-12 family members. Although related, the IL-12 family of cytokines and their receptors have distinct patterns of expression and unique effects on developing immune responses. This review summarises much of the pertinent literature on the IL-12 cytokine family and provides predictions regarding their potential therapeutic roles based on what has been learned about their functions in vitro and in vivo in gene-deficient mice.     

脓毒症患者血清促炎和抗炎细胞因子的变化

目的 检测不同病情程度的脓毒症患者血清中促炎和抗炎细胞因子的浓度,探讨不同病情程度的脓毒症患者免疫状态变化的特点和规律.方法 因子和分别收集2005年6月至2008年2月复旦大学附属中山医院急诊科收治的38例脓毒症患者和32例重症脓毒症患者的血清标本,另选15例健康成年人作为正常对照进行前瞻性研究;排除既往患有自身免疫性疾病、正在应用免疫抑制剂、AIDS以及肿瘤患者.本研究获得复旦大学附属中山医院伦理委员会的同意.采用双抗体夹心酶联免疫吸附法(ELISA)测定血清标本中炎症和抗炎症细胞因子的浓度;并采用急性生理学与慢性健康评分U(APACHEⅡ)系统对患者进行病情程度的评分.各组之间的数据比较采用方差分析,运用Stepwise方法 建立多元线性回归方程.结果 脓毒症和重症脓毒症组患者血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-1(IL-1)和白细胞介素-10(IL-10)的浓度与对照组相比明显升高,差异具有统计学意义(P<0.05);重症脓毒症组患者IL-l和Ⅱ-10的血清浓度高于脓毒症组,两组患者Ⅱ-1的浓度为26.96 ng/L和21.19 ng.L,Ⅱ-10的浓度为37.57 ng/L和26.66 ng/L,两组相比差异具有统计学意义(P<0.05).TNF-α和Ⅱ-6的质量浓度较脓毒症组下降,但仍高于正常对照组,重症脓毒症组和脓毒症组TNF-α浓度为3_4.98 ng/L和44.28 ng/L,Ⅱ-6的质量浓度分别为22.48 ng/L和26.04 ng/L,两组相比差异具有统计学意义(P<0.05).Ⅱ-1和IL-10的质量浓度与APACHEⅡ评分具有明显的相关性.建立的多元线性回归方程为:APACHEⅡ=-9.393+(IL10×0.550)+(Ⅱ,1×0.305)(F=26.198,P<0.001).结论 不同病情程度的脓毒症患者促炎和抗炎细胞因子的表达存在着明显差异,且免疫状态不同.脓毒症时主要表现为炎症反应的持续激活,重症脓毒症时抗炎症因子表达明显增加.     

肺癌患者IL-6及T淋巴细胞亚群检测的实验研究

目的 :观察肺癌患者IL -6水平及外周血T淋巴细胞亚群 ,探讨其免疫功能与临床意义的关系。方法 :采用ELISA方法检测患者血清IL -6水平。用单克隆抗体检测肺癌患者外周血中T淋巴细胞亚群。结果 :Ⅰ、Ⅱ期肺癌组与正常对照组比较 ,T淋巴细胞亚群 (CD3 、CD4、CD8)无明显差异 ,IL -6水平增高 ;Ⅲ、Ⅳ期肺癌组与正常对照组比较CD3 、CD4水平下降 ,而CD8与IL -6水平明显增高。结论 :肺癌患者IL -6及外周血T淋巴细胞亚群水平检测可反映机体免疫功能状态。对临床分析肿瘤发展状况 ,判断其预后及疗效有一定的意义。     

The role of thalidomide and placebo for the treatment of cancer-related anorexia-cachexia symptoms: results of a double-blind placebo-controlled randomized study

Abstract Objectives: To determine the effects of thalidomide and placebo on anorexia-cachexia and its related symptoms, body composition, resting metabolic rate, and serum cytokines and their receptors in patients with advanced cancer. Methods: Included in the study were patients with advanced cancer with weight loss greater than 5% in 6 months and who reported anorexia, fatigue, and one of the following: anxiety, depression, or sleep disturbances. Patients on chemotherapy within 2 weeks prior or during the study were excluded from the study. Patients were randomly assigned to either 100?mg thalidomide or placebo once a day for 14 days. The Edmonton Symptom Assessment Scale (ESAS), Functional Assessment of Anorexia/Cachexia Therapy (FAACT), Functional Assessment of Cancer Illness Therapy (FACIT-F), Hospital Anxiety Depression Scale (HADS) Pittsburgh Sleep Quality Index (PSQI) were utilized, and in addition body composition, Resting Energy Expenditure (REE), and serum cytokine levels were assessed. Results: Of the 31 patients entered in the study, 15 were assigned to the thalidomide group and 16 to the placebo group. However only 21/31 patients were able to complete the study. Compared with their baseline values, both the thalidomide and the placebo groups showed significant reduction in cytokines. Tumor necrosis factor (TNF)-α (p=0.04) and its receptors TNFR1 (p=0.04), TNFR2 (p=0.04), and interleukin (IL)-8 (p=0.04) were statistically significant in the thalidomide group. In the placebo group, TNF-α (p=0.008), TNFR1 (p=0.005), TNFR2 (p=0.005), IL-RA (p=0.005), IL-6 (p=0.005), and IL-8 (p=0.005) were statistically significant. However, improvement in these symptoms and cytokine levels were not significantly different in the thalidomide group compared with the placebo group. None of the patients withdrew from the study because of toxicity of either thalidomide or placebo. Conclusions: Based on the poor accrual rate and attrition observed in this study, it is important that future research on thalidomide as a treatment for cancer-related anorexia-cachexia symptoms (ACS) in patients with advanced cancer use less stringent entry criteria and less exhaustive outcome measures.