The relationship between muscle mass and function in cancer cachexia: smoke and mirrors?

Ramage, Michael I.; Skipworth, Richard J.E.

doi:10.1097/spc.0000000000000381

Cited by 38 publications

(36 citation statements)

References 46 publications

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“…Our findings thus support the hypothetical model proposed by Ramage et al [15] suggesting that along the trajectory of cancer cachexia, there might be a variable impact on PF outcomes depending on the magnitude of weight loss. It is possible that patients that are included in clinical trials at an early stage in the development of cancer cachexia (no/pre-cachexia), will lose muscle mass but still be able maintain functionality during the trial as they have not "reached a threshold" in which muscle loss evokes measurable functional decline.…”

Section: Discussionsupporting

confidence: 91%

“…The abundance of corresponding changes of muscle mass and grip strength reported in previous cancer cachexia trials could be due to that most patients in these studies had a baseline history of weight loss. Still, other explanations such as gender differences, the appropriateness of using upper limb strength versus leg strength, and the variability of measurement methods could also be relevant [15,21].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, a model was developed to explain the non-linear relationship between changes in muscle mass and PF outcomes in cancer cachexia [15]. This model suggests that early in the cachexia pathway, PF can be maintained despite significant loss of muscle mass, thus measurable effects on PF outcomes are small.…”

Section: Introductionmentioning

confidence: 99%

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Deterioration in Muscle Mass and Physical Function Differs According to Weight Loss History in Cancer Cachexia

Stene

Balstad

Leer

et al. 2019

Cancers

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Background: Muscle mass and physical function (PF) are common co-primary endpoints in cancer cachexia trials, but there is a lack of data on how these outcomes interact over time. The aim of this secondary analysis of data from a trial investigating multimodal intervention for cancer cachexia (ClinicalTrials.gov: NCT01419145) is to explore whether changes in muscle mass and PF are associated with weight loss and cachexia status at baseline. Methods: Secondary analysis was conducted using data from a phase II randomized controlled trial including 46 patients with stage III–IV non-small cell lung cancer (n = 26) or inoperable pancreatic cancer (n = 20) due to commence chemotherapy. Cachexia status at baseline was classified according to international consensus. Muscle mass (assessed using computed tomography (CT)) and PF outcomes, i.e., Karnofsky performance status (KPS), self-reported PF (self-PF), handgrip strength (HGS), 6-minute walk test (6MWT), and physical activity (PA), were measured at baseline and after six weeks. Results: When compared according to cachexia status at baseline, patients with no/pre-cachexia had a mean loss of muscle mass (−5.3 cm2, p = 0.020) but no statistically significant change in PF outcomes. Patients with cachexia also lost muscle mass but to a lesser extent (−2.8 cm2, p = 0.146), but demonstrated a statistically significant decline in PF; KPS (−3.8 points, p = 0.030), self-PF (−8.8 points, p = 0.027), and HGS (−2.7 kg, p = 0.026). Conclusions: Weight loss history and cachexia status at baseline are of importance if one aims to detect changes in PF outcomes in cancer cachexia trials. To improve the use of co-primary endpoints that include PF in future trials, outcomes that have the potential to detect change relative to weight loss should be investigated further.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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Deterioration in Muscle Mass and Physical Function Differs According to Weight Loss History in Cancer Cachexia

Stene

Balstad

Leer

et al. 2019

Cancers

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Section: Discussionmentioning

confidence: 99%

“…Limitations of this study include the small sample size, especially for patients with gastric (n = 5) and pancreatic (n = 5) cancers, and the absence of a functional endpoint (eg, handgrip strength, which may not correlate well with muscle mass). 43 In addition, this study was limited by the open-label and single-arm design. However, no placebo was included in this study because previous studies have shown that patients with cancer cachexia receiving placebo appeared to have decreases in LBM; therefore, any increases observed in weight-related endpoints would be because of the study drug ANAM.…”

Section: Limitationsmentioning

confidence: 99%

A multicenter, open‐label, single‐arm study of anamorelin (ONO‐7643) in advanced gastrointestinal cancer patients with cancer cachexia

Hamauchi

Furuse

Takano

et al. 2019

Cancer

126

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Background Cancer cachexia is characterized by weight loss and is associated with increased morbidity and mortality in patients with cancer. Anamorelin (ONO‐7643; ANAM) is a novel and selective ghrelin receptor agonist that improves appetite, lean body mass (LBM), body weight, and anorexia. Methods This multicenter, open‐label, single‐arm study investigated the efficacy and safety of 100 mg anamorelin in 50 Japanese patients with advanced and unresectable gastrointestinal (colorectal, gastric, or pancreatic) cancer. ANAM was administered once daily over 12 weeks. The primary endpoint was the proportion of patients that maintained or gained LBM over the course of the study. Secondary endpoints included changes in LBM, body weight, quality of life (QoL), and nutritional status biomarkers. Results The proportion of patients who responded to treatment was 63.3% (95% CI, 48.3%‐76.6%), with a least square mean ± SE change in LBM and body weight from baseline of 1.89 ± 0.36 kg and 1.41 ± 0.61 kg, respectively. Appetite‐related questions on the QoL questionnaire showed that ANAM improved appetite. Adverse events occurred in 79.6% of patients, and the most common treatment‐related adverse events were increased γ‐glutamyl transpeptidase (8.2%), diabetes mellitus (6.1%), hyperglycemia (6.1%), and prolonged QRS complex (6.1%). Conclusions ANAM improved anorexia and patients' nutritional status, resulting in rapid increases in LBM and body weight in patients with advanced gastrointestinal cancer who had cancer cachexia. ANAM treatment was well tolerated over 12 weeks. ANAM is a potential clinically beneficial pharmacotherapeutic option for patients with advanced gastrointestinal cancer who have cancer cachexia.

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Muscle weakness as an additional criterion for grading sarcopenia‐related prognosis in patients with cancer

et al. 2021

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The relationship between muscle mass and function in cancer cachexia: smoke and mirrors?

Cited by 38 publications

References 46 publications

Deterioration in Muscle Mass and Physical Function Differs According to Weight Loss History in Cancer Cachexia

Deterioration in Muscle Mass and Physical Function Differs According to Weight Loss History in Cancer Cachexia

A multicenter, open‐label, single‐arm study of anamorelin (ONO‐7643) in advanced gastrointestinal cancer patients with cancer cachexia

Muscle weakness as an additional criterion for grading sarcopenia‐related prognosis in patients with cancer

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