INTRODUCTION:

Cancer cachexia, a complex syndrome marked by gradual weight loss, muscle wasting, weakness, and fatigue, stands as a notable but frequently neglected outcome of cancer. Just like cancer itself, cancer cachexia significantly impacts patients' quality of life and general health. It afflicts a considerable portion of cancer patients, with prevalence rates differing based on tumor type and stage. Approximately 80% of individuals with advanced cancer encounter cachexia, while prevalence rates among all cancer patients fall within the range of 50% to 80%. Despite its widespread occurrence and adverse effects, cancer cachexia has historically been overlooked in both research and clinical settings.¹

Cancer cachexia has a complex impact on quality of life, deeply affecting physical well-being by inducing muscle wasting, weakness, and fatigue. It also impairs nutritional status by diminishing appetite and causing metabolic alterations. Furthermore, it often triggers emotional distress, including feelings of depression and anxiety. In addition, social interactions may also be affected as individuals grapple with self-esteem issues and limitations brought on by cancer cachexia. Furthermore, treatment tolerance and outcomes could be compromised, potentially resulting in delays or reductions in therapy efficacy. This comprehensive deterioration in quality of life emphasizes the critical requirement for holistic management approaches. These approaches should address not only the physical symptoms but also the emotional and social dimensions of cancer cachexia.² While the loss of skeletal muscle mass is a prominent feature of cancer cachexia, it's important to note that depletion of cardiac muscle also occurs, while muscle mass in other visceral organs tends to be preserved. Although cachexia is observed in different disease states, studies suggest that muscle mass loss occurs most rapidly in cancer patients.³

Moreover, effectively treating cancer cachexia poses a notable clinical challenge. Current therapeutic strategies frequently prioritize symptom management rather than targeting the root causes fueling cachexia progression. Additionally, the absence of standardized assessment tools and biomarkers complicates early detection and intervention endeavors. To tackle these obstacles, an increasing amount of research is dedicated to unraveling the molecular mechanisms behind cancer cachexia and pinpointing potential therapeutic targets. Recent studies have shed light on the involvement of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), in orchestrating muscle wasting and metabolic disturbances in cachexia.⁴

Furthermore, emerging evidence indicates that the dysregulation of crucial signaling pathways, such as the ubiquitin-proteasome and autophagy-lysosome systems, plays a role in muscle protein breakdown and subsequent loss in cachexia. Given the substantial impact of cancer cachexia on both patients' well-being and treatment outcomes, there is an urgent need to improve our understanding and management of this syndrome. Early detection, identification of biomarkers, and precise interventions are crucial for addressing the challenges presented by cancer cachexia and improving the comprehensive care offered to patients.⁵

Stages of cancer cachexia⁶:

1. Pre-Cachexia: Pre-cachexia marks the initial phase of cancer cachexia, typically marked by metabolic changes and early symptoms like decreased appetite, fatigue, and subtle shifts in body composition. Although substantial weight loss and muscle wasting might not be evident at this stage, metabolic disruptions start to emerge, setting the stage for the progression into full-fledged cachexia.

2. Cachexia: The classic phase of cancer cachexia is characterized by notable weight loss, muscle wasting, weakness, and fatigue. Alongside these physical indicators, systemic inflammation and metabolic irregularities further deteriorate the patient's general well-being. Reversing the thectic cachexia state is often challenging, necessitating comprehensive management strategies that target both the root disease process and its symptomatic effects.

3. Refractory Cachexia: Refractory cachexia signifies an advanced stage of the syndrome, often resistant to conventional treatments, where efforts to stop or reverse muscle wasting and weight loss may prove ineffective. Despite attempts to manage symptoms and enhance nutritional well-being, the cachectic condition persists, presenting substantial hurdles to patient care and prognosis. This stage highlights the critical necessity for innovative therapeutic strategies that target the intricate molecular and physiological mechanisms fueling cachexia progression.

Mechanism of cancer cachexia^7,8: The mechanism underlying cancer cachexia is intricate, involving a blend of factors such as systemic inflammation, metabolic dysregulation, and changes in protein metabolism. In individuals with cancer, a series of factors initiates a vigorous catabolic reaction, leading to excessive breakdown of fat and muscle tissues. Consequently, this process results in significant muscle depletion, which greatly impacts both morbidity and mortality rates. The metabolic shifts observed in cachexia resemble those typically seen in cases of infection rather than mere starvation, indicating a multifaceted interplay among various factors.

In contrast to weight loss caused by starvation, which primarily involves the depletion of fat stores, cancer cachexia leads to the simultaneous loss of both skeletal muscle and fat mass. One of the key metabolic disturbances in cachexia is the heightened breakdown of muscle proteins, resulting in an overall loss of muscle mass. This imbalance between the synthesis and degradation of proteins is a central aspect of metabolic disruption in cancer cachexia. Importantly, there is a notable increase in the rate of muscle protein breakdown in cachexia, coupled with a decrease in the synthesis of new proteins, ultimately tilting the balance towards net protein breakdown. Several factors contribute to the pathophysiological pathways of cancer cachexia, including:

1. Tumor-Derived Factors: Cancer cells secrete a range of molecules, including cytokines like TNF-alpha and interleukins, as well as tumor-derived factors such as proteolysis-inducing factor (PIF) and lipid-mobilizing factor (LMF). These substances directly or indirectly play roles in inducing muscle wasting and metabolic changes.

2. Systemic Inflammation: Chronic inflammation is a prominent feature of cancer cachexia. Tumor cells and immune cells within the tumor microenvironment release pro-inflammatory cytokines. These cytokines activate signaling pathways that stimulate muscle protein breakdown, suppress protein synthesis, and trigger lipolysis, ultimately resulting in muscle wasting and weight loss.

3. Neurological and Hormonal Factors: In cancer cachexia, there is dysregulation of the hypothalamus-pituitary-adrenal axis and the sympathetic nervous system. This leads to neurological signals and hormonal alterations that result in decreased appetite, heightened energy expenditure, and changes in metabolism. These factors collectively contribute to muscle wasting and weight loss in individuals affected by cancer cachexia.

4. Insulin Resistance and Metabolic Dysfunction: Cancer cachexia is linked with insulin resistance, disrupted glucose metabolism, and changes in lipid metabolism. These metabolic irregularities worsen muscle wasting and weight loss, further deteriorating the patient's nutritional well-being.

5. Muscle Protein Breakdown: Elevated activity within proteolytic pathways, including the ubiquitin-proteasome system and autophagy-lysosome pathway, accelerates the breakdown of muscle proteins. Consequently, this leads to the depletion of skeletal muscle mass, contributing to the weakness and fatigue commonly observed in cachexia.

6. Anorexia and Reduced Food Intake: Anorexia and decreased food intake are common in cancer cachexia, influenced by factors like altered taste perception, nausea, early satiety, and psychological distress. This reduction in nutrient intake exacerbates muscle wasting and weight loss, creating a vicious cycle that perpetuates the progression of cachexia.

Clinical Presentation of cancer cachexia:

Overall, the clinical presentation of cancer cachexia is characterized by a constellation of symptoms including weight loss, muscle wasting, fatigue, anorexia, metabolic disturbances, systemic symptoms, functional decline, and psychological distress.

1. Weight Loss: Unintentional weight loss is a key characteristic of cancer cachexia. Patients frequently undergo substantial and swift weight reduction, sometimes surpassing 5% of their initial body weight in a relatively brief timeframe.

2. Muscle Wasting: Cancer cachexia often presents with progressive skeletal muscle loss, termed muscle wasting or sarcopenia. This result in weakness, fatigue, and diminished functional capacity, hindering the patient's ability to carry out daily tasks.

3. Fatigue: Severe fatigue is a common occurrence in cancer cachexia, often debilitating and profoundly affecting the patient's quality of life. This fatigue may be excessive compared to the level of physical exertion and typically persists even after periods of rest.

4. Anorexia: Numerous individuals grappling with cancer cachexia encounter anorexia, marked by diminished appetite and reduced food consumption. This condition may arise from various factors, such as altered taste sensation, feelings of premature fullness, nausea, and psychological anguish.

5. Metabolic Disturbances: Metabolic changes are prevalent in cancer cachexia and often involve insulin resistance, impaired glucose tolerance, and dyslipidemia. These alterations in metabolism contribute to the heightened breakdown of muscle tissue, worsening the process of weight loss.

6. Systemic Symptoms: Individuals affected by cancer cachexia might display systemic symptoms like fever, night sweats, and overall weakness. These manifestations frequently signal the presence of the inflammatory processes that underlie the syndrome.

7. Functional Decline: Cancer cachexia often results in a deterioration of functional status and independence. Patients may encounter challenges in carrying out everyday tasks, experience decreased mobility, and notice an overall decline in physical capabilities.

8. Psychological Impact: The physical and functional limitations caused by cancer cachexia can profoundly affect patients psychologically, potentially leading to depression, anxiety, and a decrease in overall quality of life.

Management of Cancer cachexia:

The management of cancer cachexia necessitates a holistic and collaborative strategy designed to tackle the intricate interaction of physiological, nutritional, psychological, and functional elements involved in the condition. Customized treatment strategies should be crafted to cater to the unique requirements and objectives of each patient, with a primary emphasis on enhancing their quality of life and safeguarding their ability to function independently.

Pharmacological Interventions:

1. Anabolic Agents: Medications like selective androgen receptor modulators (SARMs) and ghrelin mimetics, such as anamorelin, have shown promise in promoting muscle growth and enhancing muscle strength among individuals grappling with cancer cachexia.

2. Anti-inflammatory Agents: Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are potential options for mitigating systemic inflammation and easing symptoms like fatigue and loss of appetite.

3. Appetite Stimulants: Medications such as megestrol acetate and cannabinoids, for example, dronabinol, might be recommended to stimulate appetite and boost food consumption in patients experiencing cachexia.

4. Nutritional Supplements: Nutritional supplements, whether taken orally or administered parenterally, containing protein, calories, and vital nutrients may be prescribed to enhance nutritional levels and halt further weight decline.

Nutritional Support:

1. Dietary Counseling: Registered dietitians are equipped to offer personalized dietary guidance aimed at maximizing nutrient consumption, facilitating weight stability, and addressing symptoms like anorexia and dysphagia.

2. Enteral or Parenteral Nutrition: For patients unable to meet their nutritional requirements orally, healthcare providers may consider enteral feeding through a nasogastric or gastrostomy tube, or parenteral nutrition to ensure they receive sufficient nutritional support.

Exercise and Physical Therapy:

1. Exercise Programs: Supervised exercise programs, including resistance training and aerobic exercises, may help preserve muscle mass, improve physical function, and enhance quality of life in patients with cancer cachexia.

2. Physical Therapy: Physical therapists can provide tailored exercise regimens and assistive devices to optimize mobility, reduce fatigue, and minimize functional decline.

Psychosocial Support:

Counseling and Support Groups: Psychosocial support services, including counseling, support groups, and palliative care, can help address psychological distress, improve coping strategies, and enhance overall well-being for both patients and caregivers.

Symptom Management:

1. Pain Management: Effective pain control is essential for improving quality of life in patients with advanced cancer and cachexia. Analgesic medications, interventional procedures, and complementary therapies may be utilized to manage pain effectively.

2. Fatigue Management: Energy conservation techniques, lifestyle modifications, and pharmacological interventions may be employed to manage cancer-related fatigue and improve functional status.

Clinical Trials:

Participation in clinical trials investigating novel therapeutic agents and interventions for cancer cachexia may offer promising treatment options for eligible patients.

Nurses Role in managing cancer cachexia:

Overall, nurses play a pivotal role in the multidisciplinary management of cancer cachexia by providing compassionate care, advocating for patients' needs, promoting self-management, and facilitating collaboration among healthcare team members. Their expertise and dedication contribute significantly to improving outcomes and enhancing the quality of life for patients affected by cachexia.

REFERENCES:

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7. Dhanapal R, Saraswathi T, Govind RN. Cancer cachexia. J Oral Maxillofac Pathol. 2011 Sep;15(3):257-60. doi: 10.4103/0973-029X.86670. PMID: 22144825; PMCID: PMC3227249.

8. Setiawan T, Sari IN, Wijaya YT, et al. Cancer cachexia: molecular mechanisms and treatment strategies. J Hematol Oncol. 2023; 16(1):54. doi: 10.1186/s13045-023-01454-0.

Received on 10.05.2024 Revised on 03.09.2024

Accepted on 07.11.2024 Published on 12.12.2024

Available online on December 30, 2024

Asian J. Nursing Education and Research. 2024;14(4):259-262.

DOI: 10.52711/2349-2996.2024.00051