Cancer cachexia
Cachexia-anorexia syndrome ยท CAS ยท paraneoplastic cachexia
Cancer cachexia is a multifactorial syndrome characterised by progressive involuntary weight loss with disproportionate loss of skeletal muscle (sarcopenia) and adipose tissue, that cannot be fully reversed by conventional nutritional support. It affects up to 80% of patients with advanced cancer and is responsible for ~20-30% of cancer deaths. International consensus (Fearon 2011) defines three stages: pre-cachexia, cachexia and refractory cachexia. ESMO and ASCO guidelines support multimodal management: nutritional, pharmacological, exercise and psychosocial.
Definition (Fearon 2011 international consensus)
Cancer cachexia is defined as any of:
- >5% involuntary body weight loss over 6 months (with no starvation), OR
- BMI <20 kg/mยฒ with >2% weight loss, OR
- >2% loss with sarcopenia.
Three stages:
- Pre-cachexia: โค5% weight loss + metabolic / anorexic features.
- Cachexia: >5% loss; or BMI <20 with >2% loss; or sarcopenia + >2% loss.
- Refractory cachexia: cachexia + decreased life expectancy (<3 months) + poor performance status (ECOG 3-4) + variable resistance to anticancer therapy.
Pathophysiology
- Driven by tumour-host inflammatory mediators: IL-6, TNF-ฮฑ, IL-1, IFN-ฮณ, proteolysis-inducing factor (PIF).
- Increased protein degradation via ubiquitin-proteasome and autophagy pathways.
- Decreased protein synthesis.
- Hypermetabolism.
- Insulin resistance.
- Lipid mobilisation via lipid-mobilising factor.
- Anorexia driven by hypothalamic appetite regulation disruption (POMC, NPY, leptin, ghrelin axis).
- Sarcopenic obesity: loss of muscle mass despite preserved / increased fat โ adverse prognostic feature.
Assessment
- Detailed weight history (3 / 6 / 12 month timeline).
- Anthropometry: weight, BMI, mid-arm muscle circumference.
- Hand-grip dynamometry.
- Body composition:
- DEXA scan โ body composition gold standard.
- CT psoas / L3 cross-sectional analysis โ sarcopenia.
- Bioimpedance.
- Bloods: FBC, CRP, albumin, prealbumin, transferrin, U&E, LFT, glucose, calcium, magnesium, phosphate, zinc.
- Dietitian-led detailed 3-day food diary.
- Performance status (ECOG, Karnofsky).
- Symptom screening (ESAS).
Management
- Multimodal approach recommended (Fearon model; ESMO).
- Nutritional:
- Dietetic review; high-protein high-calorie diet (1.2-1.5 g/kg protein).
- Oral nutritional supplements (Fortisip, Ensure).
- Enteral / parenteral feeding only in selected cases (clinical benefit > burden).
- Pharmacological:
- Progestogens: megestrol acetate 320-800 mg / day; medroxyprogesterone โ improves appetite, weight (mostly fat); VTE risk.
- Corticosteroids: dexamethasone 2-8 mg / day; short-term appetite stimulant; reserve for advanced disease.
- Olanzapine low-dose (2.5-5 mg) โ emerging evidence for appetite stimulation and weight.
- Anamorelin (ghrelin agonist; ONO-7643) โ approved in Japan; EMA refused marketing authorisation; not licensed/available in the UK.
- Mirtazapine โ secondary appetite effect.
- Exercise: resistance + aerobic; supervised programmes; oncology rehab.
- Psychosocial: family / carer support; counsel re tube-feeding burdens; end-of-life planning when refractory.
- Treat reversible factors: pain, constipation, mucositis, nausea, dysphagia, dental.
- Refractory cachexia: palliative goals; symptom control; family support.
References
- Fearon K et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011;12:489-495.
- Roeland EJ et al. Management of cancer cachexia: ASCO guideline. J Clin Oncol. 2020;38:2438-2453.
- Arends J et al. ESMO clinical practice guideline: cancer cachexia in adult patients. ESMO Open. 2021;6:100092.
- Temel JS et al. Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 / 2). Lancet Oncol. 2016;17:519-531.
- Macmillan Cancer Support. Eating difficulties and weight loss. London: Macmillan; 2024.
Spot a correction?
If any clinical statement, citation or link on this page needs updating, please email admin@skinoncology.net with the page name, the proposed correction and the supporting source.