Randomized Phase III Clinical Trial of Five Different Arms of Treatment in 332 Patients with Cancer Cachexia

Mantovani, Giovanni; Macciò, Antonio; Madeddu, Clelia; Serpe, Roberto; Massa, Elena; Dessì, Mariele; Panzone, Filomena; Contu, Paolo

doi:10.1634/theoncologist.2009-0153

Cited by 191 publications

(213 citation statements)

References 61 publications

(60 reference statements)

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“…In particular, multimodal trials have been recommended; however, the majority of cachexia trials have used single agents in isolation, or have lacked a comparator arm 23, 24. Where multimodal trials have been done,25, 26, 27 these have examined two or more components, and whilst some findings have been encouraging, to date, there have been no randomised trials integrating all the components we consider to be appropriate and this has resulted in a failure to advance cachexia treatment 28. Our findings suggest that multimodal cachexia intervention is safe and feasible and support further examination of this approach to fully assess effects on weight and lean body mass in larger trials.…”

Section: Discussionmentioning

confidence: 99%

A randomized phase II feasibility trial of a multimodal intervention for the management of cachexia in lung and pancreatic cancer

Solheim

Laird

Balstad

et al. 2017

J cachexia sarcopenia muscle

237

262

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BackgroundCancer cachexia is a syndrome of weight loss (including muscle and fat), anorexia, and decreased physical function. It has been suggested that the optimal treatment for cachexia should be a multimodal intervention. The primary aim of this study was to examine the feasibility and safety of a multimodal intervention (n‐3 polyunsaturated fatty acid nutritional supplements, exercise, and anti‐inflammatory medication: celecoxib) for cancer cachexia in patients with incurable lung or pancreatic cancer, undergoing chemotherapy.MethodsPatients receiving two cycles of standard chemotherapy were randomized to either the multimodal cachexia intervention or standard care. Primary outcome measures were feasibility assessed by recruitment, attrition, and compliance with intervention (>50% of components in >50% of patients). Key secondary outcomes were change in weight, muscle mass, physical activity, safety, and survival.ResultsThree hundred and ninety‐nine were screened resulting in 46 patients recruited (11.5%). Twenty five patients were randomized to the treatment and 21 as controls. Forty‐one completed the study (attrition rate 11%). Compliance to the individual components of the intervention was 76% for celecoxib, 60% for exercise, and 48% for nutritional supplements. As expected from the sample size, there was no statistically significant effect on physical activity or muscle mass. There were no intervention‐related Serious Adverse Events and survival was similar between the groups.ConclusionsA multimodal cachexia intervention is feasible and safe in patients with incurable lung or pancreatic cancer; however, compliance to nutritional supplements was suboptimal. A phase III study is now underway to assess fully the effect of the intervention.

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Section: Discussionmentioning

confidence: 99%

A randomized phase II feasibility trial of a multimodal intervention for the management of cachexia in lung and pancreatic cancer

Solheim

Laird

Balstad

et al. 2017

J cachexia sarcopenia muscle

237

262

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“…Compared with prior studies, 4,7,13,15 this is the first to investigate the effect of thalidomide and placebo using validated ACS measures and cytokines. However compared with prior studies, our sample size was smaller, we had a high rate of the attrition, and noncompliance rates were higher.…”

Section: Discussionmentioning

confidence: 99%

“…[4][5][6] Various treatments have been investigated for ACS; however, they were found to be of limited efficacy in improving ACS. 2,5,7 There has been renewed interest in the use of thalidomide for ACS. 7 This interest is based on previous studies using thalidomide for the treatment of acquired immunodeficiency syndrome (AIDS)-associated cachexia 8 and the effects of thalidomide in modulating the release of cytokines such as tumor necrosis factor (TNF)-a and interleukin (IL)-10.…”

Section: Introductionmentioning

confidence: 99%

“…2,5,7 There has been renewed interest in the use of thalidomide for ACS. 7 This interest is based on previous studies using thalidomide for the treatment of acquired immunodeficiency syndrome (AIDS)-associated cachexia 8 and the effects of thalidomide in modulating the release of cytokines such as tumor necrosis factor (TNF)-a and interleukin (IL)-10. 9 It acts on the inflammatory pathways that contribute to the pathophysiology of ACS.…”

Section: Introductionmentioning

confidence: 99%

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The Role of Thalidomide and Placebo for the Treatment of Cancer-Related Anorexia-Cachexia Symptoms: Results of a Double-Blind Placebo-Controlled Randomized Study

Yennurajalingam

Willey

Palmer

et al. 2012

Journal of Palliative Medicine

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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.

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“…Patients with metastatic cancer receiving thalidomide showed improvement of quality of life (Bruera et al, 1999), weight loss (Khan et al, 2003, Gordon et al, 2005, lean body mass and physical functions (Gordon et al, 2005). Finally, a large randomised trial including cachectic cancer patients showed that thalidomide alone is less effective that its combination with other treatments (Mantovani, 2010). More recently an experimental study reported that thalidomide inhibits an E3 ubiquitin ligase complex involved in embryonal development (Ito et al, 2010), leading to hypothesize that thalidomide effectiveness on muscle wasting in cancer hosts could be achieved through inhibition of muscle-specific ubiquitin ligases.…”

Section: Inhibition Of Cytokine Productionmentioning

confidence: 99%

Mechanism-Based Therapeutic Approaches to Cachexia

et al. 2013

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Cachexia is a multifactorial syndrome characterized by body weight loss, depletion of adipose tissue and skeletal muscle mass, and marked alterations of the metabolic homeostasis.The occurrence of cachexia significantly impinges on patient's morbidity and mortality, and on quality of life. Inflammation, anorexia/malnutrition, alterations of protein and lipid metabolism are among the main mechanisms involved in the development of cachexia. While anorexia and malnutrition are long known contributing factors, the mechanisms leading to inflammation and metabolic alterations were clarified later on. On these premises, several therapeutic approaches were proposed. Most of them are in the pre-clinical phase, but some already reached the clinical experimentation. The present review will focus on treatment options proposed on the basis of mechanistic alterations. In this regard, in addition to nutritional and anti-inflammatory strategies, also approaches based on perturbation of specific signal transduction pathways are taken into consideration.

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Randomized Phase III Clinical Trial of Five Different Arms of Treatment in 332 Patients with Cancer Cachexia

Cited by 191 publications

References 61 publications

A randomized phase II feasibility trial of a multimodal intervention for the management of cachexia in lung and pancreatic cancer

A randomized phase II feasibility trial of a multimodal intervention for the management of cachexia in lung and pancreatic cancer

The Role of Thalidomide and Placebo for the Treatment of Cancer-Related Anorexia-Cachexia Symptoms: Results of a Double-Blind Placebo-Controlled Randomized Study

Mechanism-Based Therapeutic Approaches to Cachexia

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