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)-a ( 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-a ( 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.

The Relationship Between Inflammatory Biomarkers and Symptom Distress in Lung Cancer Patients Undergoing Chemotherapy

“…Generally, IL-6, IL-8, and CRP have been reported to be the inflammation biomarkers in cancer patients for the monitoring of clinical symptoms, suggesting that these cytokines are positively related to the scores of the physical or psychological symptoms. 36,49,50 Herein, chemotherapy had reduced the expressions in IL-6, IL-8, and CRP from T1 to T2 (Table 3). At T3, IL-6 subsequently increased, but both IL-8 and CRP continuously reduced.…”

Update on interventions focused on symptom clusters

“…Technology may potentially reduce the attrition. However, further studies are required to confirm [45]. We were unable to determine that any specific symptom cluster was more likely to respond to an intervention.…”

The effects of dexamethasone and placebo on symptom clusters in advanced cancer patients: A preliminary report.

“…Therefore, these studies have not considered the potential effects (beneficial or deleterious) of the interventions on other symptoms that may affect the patient's quality of life. Second, even in intervention studies that have targeted a symptom cluster, most have used nonpharmacological interventions [15,57].The current study is the first pharmacological study [15,58,59] to target a symptom cluster in advanced cancer. Third, our study is unique in that it tested the effects of a drug (dexamethasone) known to affect the common pathway of causation (inflammation [15,21]) of all the symptoms in the cluster.The positive response of fatigue and anorexia/cachexia to dexamethasone further substantiates the close association of these symptoms and the need to treat both symptoms together rather than individually.…”