Thalidomide for managing cancer cachexia

Reid, Joanne; Mills, Moyra; Cantwell, Marie; Cardwell, Christopher; Murray, Liam; Donnelly, Michael

doi:10.1002/14651858.cd008664.pub2

Cited by 50 publications

(28 citation statements)

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“…In a randomized, placebo-controlled trial, thalidomide was found to be well tolerated and effective in slowing weight loss and improving arm muscle mass and physical function in 33 patients with advanced pancreatic cancer and CACS 36. Recently, a meta-analysis was performed to assess whether thalidomide is an effective treatment for CACS,37 and the authors concluded that there is inadequate evidence to recommend the use of this drug in clinical practice. Further large, well conducted, randomized controlled trials are needed to assess properly the true benefits of thalidomide alone and in combination in CSCS.…”

Section: Drugs With Confirmed Clinical Resultsmentioning

confidence: 99%

Drugs in development for treatment of patients with cancer-related anorexia and cachexia syndrome

Mantovani¹,

Madeddu²,

Macciò³

2013

DDDT

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Cancer-related anorexia and cachexia syndrome (CACS) is a complex multifactorial condition, with loss of lean body mass, chronic inflammation, severe metabolic derangements, reduced food intake, reduced physical activity, and poor quality of life as key symptoms. Cachexia recognizes different phases or stages, moving from precachexia through overt cachexia to advanced or refractory cachexia. The purpose of this review is to describe currently effective approaches for the treatment of cachexia, moving forward to drugs and treatments already shown to be effective but needing further clinical trials to confirm their efficacy. We then introduce novel promising investigational drugs and approaches which, based on a strong rationale from the most recent data on the molecular targets/pathways driving the pathophysiology of cachexia, need to be tested either in currently ongoing or appropriate future clinical trials to confirm their clinical potential. Although different drugs and treatments have been tested, we can speculate that a single therapy may not be completely successful. Indeed, considering the complex clinical picture and the multifactorial pathogenesis of CACS, we believe that its clinical management requires a multidisciplinary and multitargeted approach. In our opinion, appropriate treatment for cachexia should target the following conditions: inflammatory status, oxidative stress, nutritional disorders, muscle catabolism, immunosuppression, quality of life, and above all, fatigue. A comprehensive list of the most interesting and effective multitargeted treatments is reported and discussed, with the aim of suggesting the most promising with regard to clinical outcome. A critical issue is that of testing therapies at the earliest stages of cachexia, possibly at the precachexia stage, with the aim of preventing or delaying the development of overt cachexia and thereby obtaining the best possible clinical outcome for patients.

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Section: Drugs With Confirmed Clinical Resultsmentioning

confidence: 99%

Drugs in development for treatment of patients with cancer-related anorexia and cachexia syndrome

Mantovani¹,

Madeddu²,

Macciò³

2013

DDDT

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“…In contrast, cancer cachexia treatment with thalidomide, a drug with potent anti-inflammatory effects (Moreira et al 1993, Fujita et al 2001, Keifer et al 2001, Richardson et al 2002 presented encouraging preliminary results (Davis et al 2012), but we still do not have sufficient data to recommend this drug in clinical practice (Reid et al 2012).…”

Section: New Perspectives For the Treatment Of Cancer Cachexiamentioning

confidence: 98%

Molecular and neuroendocrine mechanisms of cancer cachexia

Mendes

Pimentel

Costa

et al. 2015

Journal of Endocrinology

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Cancer and its morbidities, such as cancer cachexia, constitute a major public health problem. Although cancer cachexia has afflicted humanity for centuries, its underlying multifactorial and complex physiopathology has hindered the understanding of its mechanism. During the last few decades we have witnessed a dramatic increase in the understanding of cancer cachexia pathophysiology. Anorexia and muscle and adipose tissue wasting are the main features of cancer cachexia. These apparently independent symptoms have humoral factors secreted by the tumor as a common cause. Importantly, the hypothalamus has emerged as an organ that senses the peripheral signals emanating from the tumoral environment, and not only elicits anorexia but also contributes to the development of muscle and adipose tissue loss. Herein, we review the roles of factors secreted by the tumor and its effects on the hypothalamus, muscle and adipose tissue, as well as highlighting the key targets that are being exploited for cancer cachexia treatment.

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“…At present, this drug is approved for multiple myeloma and currently used experimentally to treat various cancers, dermatological, neurological and inflammatory diseases [6,7,8]. The clinical use of thalidomide in CACS is still controversial despite some researches indicating that orally administered thalidomide could improve CACS symptoms and patient quality of life (QoL) [9,10]. …”

Section: Introductionmentioning

confidence: 99%

Clinical Studies on the Treatment of Cancer Cachexia with Megestrol Acetate plus Thalidomide

Wen

Cao

et al. 2012

Chemotherapy

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Background: The management of cancer-related anorexia/cachexia syndrome (CACS) is a great challenge in clinical practice. To date, practice guidelines for the prevention and treatment of CACS are lacking. The authors conducted a randomized study to confirm the effectiveness and safety of treatment of CACS utilizing megestrol acetate (MA) plus thalidomide. Methods: One hundred and two candidates with CACS were randomly assigned to two treatment groups (trial group and control group): the trial group received MA (160 mg po, bid) plus thalidomide (50 mg po, bid), while the control group received MA (160 mg po, bid) alone. Treatment duration was 8 weeks. Results: Analysis of the trial group demonstrated a significant increase from baseline in body weight (<0.01), quality of life (p = 0.02), appetite (p = 0.01), and grip strength (p = 0.01), and a significant decrease in fatigue, Glasgow Prognostic Score (p = 0.05), Eastern Cooperative Oncology Group performance status (p = 0.03), IL-6 (p < 0.01), and tumor necrosis factor-α (p = 0.02). In contrast, in the control group, endpoints with a significant improvement from baseline included body weight (p < 0.02) and appetite (p = 0.02). The mean changes in the endpoints from baseline in the trial group were significantly greater compared with the control group: in the primary endpoints, body weight (p = 0.05), fatigue (p < 0.01) and quality of life (p = 0.01), and in the secondary endpoints, grip strength (p = 0.05), Glasgow Prognostic Score (p = 0.02), Eastern Cooperative Oncology Group performance status (p = 0.02), IL-6 (p < 0.01) and tumor necrosis factor-α (p = 0.01). Toxicity was found to be relatively negligible in both groups. Conclusion: A combination regimen of MA and thalidomide is more effective than MA alone in the treatment of CACS.

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Thalidomide for managing cancer cachexia

Abstract: Mantovani 2010b Mantovani G. Randomised phase III clinical trial of 5 di erent arms of treatment on 332 patients with cancer cachexia.

Cited by 50 publications

References 50 publications

Drugs in development for treatment of patients with cancer-related anorexia and cachexia syndrome

Drugs in development for treatment of patients with cancer-related anorexia and cachexia syndrome

Molecular and neuroendocrine mechanisms of cancer cachexia

Clinical Studies on the Treatment of Cancer Cachexia with Megestrol Acetate plus Thalidomide

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