Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 
  • Users Online: 308
  • Home
  • Print this page
  • Email this page

 Table of Contents  
REVIEW ARTICLE
Year : 2021  |  Volume : 8  |  Issue : 5  |  Page : 508-518

Revisiting Cancer Cachexia: Pathogenesis, Diagnosis, and Current Treatment Approaches


1 Department of Paediatric Rehabilitation, Yenepoya Physiotherapy College, Yenepoya (Deemed to be University), Mangalore, Karnataka, India
2 Department of Oral Medicine and Radiology, Yenepoya Dental College, Yenepoya (Deemed to be University), Mangalore, Karnataka, India

Date of Submission09-Apr-2021
Date of Acceptance15-Apr-2021
Date of Web Publication27-Aug-2021

Correspondence Address:
Sajad Ahmad Buch
Department of Oral Medicine and Radiology, Yenepoya Dental College, Yenepoya (Deemed to be University), Mangalore, Karnataka
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/apjon.apjon-2126

Rights and Permissions
  Abstract 


The objective of this article is to group together various management strategies and to highlight the recent treatment modifications that attempt to target the multimodal etiological factors involved in cancer cachexia. The contemporary role of nursing fraternity in psychosocial and nutritional assessment of cancer patients is briefly discussed. Cachexia is a syndrome of metabolic disturbance, characterized by the inflammation and loss of muscle with or without loss of adipose tissue. In cancer cachexia, a multifaceted condition, patients suffer from loss of body weight that leads to a negative impact on the quality of life and survival of the patients. The main cancers associated with cachexia are that of pancreas, stomach, lung, esophagus, liver, and that of bowel. The changes include increased proteolysis, lipolysis, insulin resistance, high energy expenditure, and reduced intake of food, all leading to impaired response to different treatments. There is no standardized treatment for cancer cachexia that can stabilize or reverse this complex metabolic disorder at present. The mainstay of cancer cachexia therapy remains to be sufficient nutritional supplements with on-going efforts to explore the drugs that target heightened catabolic processes and complex inflammation. There is a need to develop a multimodal treatment approach combining pharmacology, exercise program, and nutritional support to target anorexia and the severe metabolic changes encountered in cancer cachexia.

Keywords: Body weight, cancer cachexia, grehlin, lean body mass, muscle tissue, review


How to cite this article:
Baba MR, Buch SA. Revisiting Cancer Cachexia: Pathogenesis, Diagnosis, and Current Treatment Approaches. Asia Pac J Oncol Nurs 2021;8:508-18

How to cite this URL:
Baba MR, Buch SA. Revisiting Cancer Cachexia: Pathogenesis, Diagnosis, and Current Treatment Approaches. Asia Pac J Oncol Nurs [serial online] 2021 [cited 2021 Sep 23];8:508-18. Available from: https://www.apjon.org/text.asp?2021/8/5/508/324773




  Introduction Top


The term “cachexia” derived from the Greek “kakos” (bad) and “hexis” (condition) is a syndrome of multiple organs associated with cancer and various systemic disorders and is characterized by the systemic inflammation and loss of body weight (at least 5%) because of extensive wasting of the skeletal muscle and adipose tissue.[1] Other than cancer, cachexia can also occur in other chronic conditions such as chronic obstructive pulmonary disease, congestive heart failure, chronic kidney disease, and the AIDS.[2],[3] Cancer cachexia occurs in more than half of all the cancer cases. The various abnormalities associated with cancer cachexia include alterations in carbohydrate, protein, and lipid metabolism, and that of insulin resistance, anorexia, with overwhelming degradation of muscle proteins.[4] The sequelae of cachexia include muscle wasting, edema, anemia, fatigue, and gustatory changes, that result in compromised physical function, heightened treatment-associated toxicity, and a poor prognosis.[5] Cancer cachexia leads to progressive and irreversible functional impairment even in the presence of adequate nutritional support.[6] The loss of muscle mass in cancer cachexia occurs at a rapid rate in comparison to cachexia attributed to other disease states.[7] The highest affliction of cancer cachexia is seen in gastric and pancreatic cancer (up to 80%), and the least incidence is reported in leukemia and breast cancer (up to 40%).[8] However, palliative care studies have revealed that irrespective of the cancer site, cachexia rates are uniformly substantial in the number near the end of the life.[9] There is a lack of consensus as to the proportion of deaths due to cancer cachexia owing to the complexity of the disease, but it can have both direct and indirect contribution for the significant proportion of cancer-related deaths, besides causing a negative impact on quality of life (QOL), chemotherapy response, and overall survival.


  Pathogenesis Top


The three factors that play a vital role in cancer cachexia syndrome include (1) negative energy balance secondary to metabolic dysregulation, (2) increased breakdown of fat and proteins due to very high catabolic drive, and (3) neurohormonal dysregulation [Figure 1].[10] The various disease-related states, such as pain, depression, impact of multimodal therapeutic modalities, uncertainty about various foods, and the burden of diseases per se can lead to inadequate intake of energy-protein foods.[11],[12] However, reduced energy intake is not as significant a factor in ensuing cachexia as tumor and tumor microenvironment. There is evidence that proinflammatory cytokines are up regulated, altering patient's metabolism, especially their energy expenditure, along with the metabolism of muscle and adipose tissue.[4],[13],[14] Several proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-1 and-6 (IL-1/IL-6) play a vital role promoting cachexia.[15] TNF-α has been seen to hamper the differentiation of fat and muscle cells resulting in the insulin resistance.[16],[17],[18] It is probably the most talked about cytokine due to its role in the promotion of anorexia and wasting of skeletal muscle through nuclear factor-KB pathway.[19] TNF-α boosts gluconeogenesis, breakdown of fats and proteins, and thereby suppresses the synthesis of lipids, proteins, and glycogen.[20] Elevated levels of both the IL-1 and IL-6 are reported in cachexia associated with cancer. Increased IL-1 levels in cachectic state cause an increase in tryptophan concentrations, inducing feeling of fullness, and hunger suppression.[21] IL-6 has a direct effects on muscle and fat wasting in addition to effecting acute-phase response and metabolic remodeling of the liver.[22] The origin of IL-6 is both from the immune system and from the tumor itself,[23] pointing out at a direct role of tumor cells in the establishment of cachexia. IL-6 seemingly has a significant role in cachexia development, but it is not considered as the sole agent to induce such changes, working in an indirect fashion, shown by its failure to cause cachexia in animal model.[16] Similarly targeting TNF-α alone to prevent the development of cachexia did not reveal any benefits when neutralizing antibodies were used against it.[24] Therefore, it seems that a teamwork of these factors is important for the development of cachexia, rather than any one of them working alone.[25]
Figure 1: Pathophysiology of cancer cachexia. LMF: Lipid-mobilizing factor, IL-1: Interleukin 1; TNF-α: Tumor necrosis factor a; APP: Acute phase proteins' GH: Growth harmone, CRF: Corticotropin-releasing factor

Click here to view


Increased levels of proinflammatory cytokines (IL-1α, IL-6, and TNF-α) in participants with advanced cancer suggested a strong and collective network encouraging cachexia.[15] Systemic inflammation in cachectic models of mice and in patients with cachexia is a result of co-operation among numerous proinflammatory cytokines.[10] Various studies that established the role of proinflammatory cytokines in the pathogenesis of cachexia are shown in [Table 1].[26],[27],[28],[29],[30],[31],[32],[33]
Table 1: Cytokines mainly responsible in the pathogenesis of cachexia

Click here to view



  Diagnosis of Cancer Cachexia Top


Body mass index (BMI) is not a defining factor for cancer cachexia. Patients who are obese may have adequate BMI but deficient lean body mass (sarcopenia), commonly seen in cancer patients.[34] Research has improved our knowledge of underlying features that lead to cancer cachexia, now known as a multifaceted syndrome associated with loss of muscle mass with or without loss of adipose tissue propelled by reduced energy intake and further changes in the metabolism.[35] As a result, the criteria used now to define cancer cachexia include loss of body weight, low skeletal muscle mass and BMI, reduced energy intake, proinflammatory markers, and metabolic alterations as shown in [Table 2].[6],[36],[37]
Table 2: Cancer cachexia defining criteria

Click here to view



  Skeletal Muscle Wasting Top


Muscle wasting is a principal factor in cancer cachexia which leads to compromised life quality, disruption in normal functioning, and interferes with the prognosis. The weakness associated with muscle atrophy could result in reduced mobility, fatigue, and a chance of respiratory failure which accounts for the large number of cancer deaths.[38] In general, the process of muscle wasting is due to an imbalance between the synthesis of proteins and their degradation. Although it is suggested that both anabolic and catabolic reactions have a role in cachexia, most of the studies have stressed on the mechanism of induced proteolysis. The studies conducted on animal models have established the activation of ubiquitin proteasome pathway causing degradation of proteins leading to muscle wasting; however, it is not proven yet if such proteasomal degradation can have similar substantial effect in cachetic patients.[39],[40]

Autophagy too has evoked a great interest in the process of skeletal muscle wasting in cancer cachexia.[41],[42],[43] Various studies carried out in animal models as well as in humans have contemplated the role of autophagy in the wasting disease in cachetic patients.[10],[44] Autophagy mediators, LC3B (Protein) and BNIP3 (messenger RNA)[45] in lung cancer, and GABARAPL1 (lysosomal vesicles interactor and autophagy inducer)[46] in gastrointestinal cancer were found be upregulated. Another possible mechanism for skeletal muscle wasting has been attributed to calpain proteases,[47] although there is only little information about these proteases having any substantial role in muscle wasting.[48]

All these changes in cachexia are not restricted to skeletal muscle only and being a multiorgan syndrome involves other tissues as well; adipose, liver, kidneys, brain, and many more. The need of the hour is to decode the mediators of all the tissues involved, and to amplify our existing knowledge about causative factors in cancer cachexia.


  Treatment of Cancer Cachexia Top


Despite its high clinical relevance, cancer cachexia is still an underrated and more often remains out of focus during the treatment of cancers. It has increasingly become clear that cancer cachexia being a multiorgan syndrome with multitude of factors involved in it, needs a combined approach (nutrient supply, exercise, drugs, etc.) for its management. Therefore, new cancer cachexia management protocols advise amalgamation of nutritional support, drugs and exercise therapy; the latter having additional benefit on QOL in cancer patients irrespective of cachexia.[49],[50] Similarly, nutritional support is very important in cancer patients, as food intake is usually compromised secondary to anorexia, nausea, vomiting, and oral mucositis.[8] Therefore, immediately after the diagnosis of cancer, the patients should be monitored for any nutritional indices and administered nutritional and catabolic support.[51] In cancer cachetic patients, the average daily intake of proteins is about 0.7–1.0 g/kg of body weight.[52] An increase of 300–400 kcal and 50% of extraprotein is required daily for an effective anabolic resistance. A favorable effect in cachetic states was seen with some nutritional supplements such as β-hydroxy-β-methylbutyrate (HMB),[53],[54] eico-sapentaenoic acid,[55],[56] and with L-carnitine.[57],[58] However, recent review pointed out at limited evidence in favor of using HMB and L-carnitine.[59] In the past, the beneficial effects of omega-3 fatty acids in cancer cachexia were not proven,[60],[61],[62] but the studies conducted recently with improved designs favor their use in cachetic patients.[63],[64] The route of administration should be preferably enteral, only switching to parenteral route if maintaining adequate supplements becomes difficult through enteral route.[65]


  Existing pharmacological agents for cancer cachexia Top


The pharmacological agents that target proinflammatory cytokines (or their associated receptors) have been widely studied due to a major role of systemic inflammation in the pathogenesis of cancer cachexia. Furthermore, other agents that stimulate appetite and help in weight gain also have enjoyed a greater role against cancer cachexia.

Proinflammatory cytokine inhibitors

Neither Etanercept[66] nor Infliximab,[24] both anti-TNF-α could prevent atrophy of skeletal muscle or improve appetite, in two randomized clinical trials in cachetic terminally ill patients. Similarly, Thalidomide[67],[68],[69] in three clinical trials and Pentoxifylline[70],[71] in two showed only modest gain in muscle mass, but with aggravation of life or showed no noteworthy clinical effects. Clazakizumab, humanized anti-IL-6 monoclonal antibody in a phase I clinical trial led to an increase in hemoglobin and albumin levels and also relieved fatigue in patients with advanced cancer.[72] The monoclonal antibody caused reduction in the depletion of lean mass in patients with non-small cell lung carcinoma during a subsequent Phase II trial.[73] Xilonix, capable of down-regulating IL-1α was able to halt changes in body composition when used in a Phase I clinical trial in refractory cancer,[74] and in a Phase III clinical trial in patients with cachexia in advanced colorectal cancer.[75] Ruxolitinib, selective JAK1/2 inhibitor, used in patients with myelofibrosis, led to only a minimal increase in the size of the spleen and added on lean body mass increasing body weight in a significant proportion.[76] Ruxolitinib was included further in an open-label Phase II trial (NCT02072057) in 2014 to test its safety, efficacy, and its effect on overall survival, but the trial was ultimately aborted in 2019 due to unsuccessful recruitment.

Grehlin and anamorelin

Grehlin is a peptide hormone secreted mainly by the stomach and plays a vital role in hunger and maintains a balanced energy state. A high dose of subcutaneous 13 μg/kg or a low dose of 0.7 μg/kg Grehlin was administered to gastrointestinal cancer patients daily for 8 weeks.[77] There was improvement in appetite with reduced loss of fat in high dose group as compared to that of low dose group. Lean body mass showed an insignificant increase in the high dose group. In another study (Phase II randomized clinical trial), increased intake of food and appetite was seen in esophageal cancer patients during grehlin use (intravenous 3 μg/kg), and reduced nausea and anorexia reported during chemotherapy treatment.[78] Inconsistent results with grehlin were reported in few studies in which grehlin caused loss of appetite despite a state of hyper-grehlinemia.[79] This may be attributed to a short half-life (30 min) of grehlin.[80],[81] This created a pursuit to find other agents that could efficiently target the grehlin axis. Anamorelin, a valid synthetic agonist of grehlin system mimics N-terminal active core of ghrelin. It qualifies for regulating the grehlin axis with an advantage of oral administration and having a half-life of 7 h.[82] In a Phase I trial, Anamorelin showed significant dose-dependent weight gain, with no notable adverse effects.[83] Similarly, several studies such as ROMANA[84],[85] favored Anamorelin and reported increased appetite, lean body mass, but no benefits on hand grip strength and QOL; the reason US Food and Drug Administration (FDA) is yet to provide approval for its use. However, Anamorelin was approved for the use in Japan on December 11, 2020, based on the results of two studies[86],[87] that showed increase in lean body mass, evaluated by dual-energy X-ray absorptiometry. One of the studies did show unfavorable results on muscle hand strength while the other did not account for functional endpoints such as muscle or physical strength.[88]

Progestins

US FDA allowed the use of megestrol acetate in 1993 for anorexia, unexplained weight loss, and cachexia associated with AIDS. Megestrol is derived from progesterone and is capable of stimulating appetite, thereby improving calorific intake and nutritional status. A meta-analysis incorporating 35 clinical trials studying the effect of megestrol in 3963 patients reported a dose-dependent increase in both the appetite and weight in cancer patients.[89] The megestrol probably has anti-inflammatory action because it is capable of down regulating the levels of proinflammatory cytokines or their associated receptors.[90],[91] Medroxyprogesterone, another derivative of progesterone has also been seen to inhibit proinflammatory cytokines, particularly TNF-α, IL-1, and IL-6;[90],[92] therefore, has been considered for the use in cancer-related anorexia and cachexia. It improves anorexia, QOL, and increases body weight, although the latter is due to its effects on adipose tissue rather than the actual lean body mass.

Corticosteroids

Different corticosteroids, dexamethasone (3–6 mg/day), methylprednisolone (12 mg/day), and prednisone (15 mg/day) leads to increased appetite and weight gain.[93] However, the effect is temporary and associated with adverse effects such as insulin resistance, adrenal insufficiency, myopathy, fluid retention, and sleep disorders.[94],[95] Due to their long-term side effects, corticosteroids are restricted in use, only for rapid and short action and in few selected cases of cachexia only.[93]

Nonsteroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been considered because of their effect on inflammation. Celecoxib or a placebo was randomly given to 11 patients with gastrointestinal or head and neck cancer for 21 days in a Phase II clinical pilot trial.[96] Body weight, BMI, and QOL showed significant increase in celecoxib group, while as all these parameters declined in the placebo group. In another Phase II trial, 300 mg/day of celecoxib was administered for 4 months in 24 advanced cancer patients.[97] The results showed a significant increase in lean body mass, down regulation of TNF-α increased hand grip strength, QOL and raised performance status. However, later two systematic reviews concluded that insufficient studies have been conducted to substantiate the effectiveness of NSAIDs in cancer cachexia,[98] also there is weak evidence to advocate use of NSAIDs despite no notable toxicity reports subsequent to their use in cancer cachexia.[99]

Cannabinoids

A class of heterogeneous compounds in marijuana, cannabinoids activate the receptors on certain cells that subdue release of neurotransmitters in brain. Cannabinoids occur naturally in cannabis plants and phytocannabinoid, tetrahydrocannabinol (THC) probably increases appetite, body fat level, nutritional intake, body weight, and improves QOL.[100] A Phase III clinical trial showed no significant changes in appetite and QOL when compared with a placebo.[101] However, a double-blind, placebo-controlled pilot trial with THC showed usefulness in abatement of chemosensory changes and it increased urge for high protein diet.[102] A recent pilot study carried on advanced cancer patients reported promising results with 5 mg/day or 10 mg/day in two divided doses of THC without any significant adverse reactions, justifying further large scale studies with regulated doses of cannabis in cancer cachexia.[103] Synthesized versions, nabilone and dronabinol have also been given potential considerations for use in cachexia.

Multimodal treatments

No multimodal treatment protocol for cachexia or extensive wasting has been standardized till date. The complexity of pathogenesis in cancer cachexia (multisystem syndrome) has led to growing considerations for multimodal treatment protocols. A critical review of the literature published between January 2008 and December 2019 was conducted to evaluate the multiple modal treatments for all types of cachexia.[104] A Phase II multimodal feasibility trial used resistance training, oral nutritional supplements, and celecoxib for cancer cachexia in patients with pancreatic or incurable lung cancer, undergoing chemotherapy.[105] No significant effects on physical activity or muscle gain were noticed probably due to sample size restrictions. The absence of any serious side effects during this trial possibly makes multimodal treatment safe and practicable; a Phase III trial was on going to evaluate the efficacy of the intervention.

A randomized controlled trial implementing nutritional support together with an exercise program (60 min exercise twice a week), did not show any improvement in QOL, but a good percentage (67%) of patients adhered to the intervention, showed reduction in nausea and vomiting and increase protein intake.[106] Larger trials are the need of the hour to assess the effect of combined nutrition and exercise in cancer cachexia.

A clinical study was conducted on two groups of cancer-related anorexia/cancer cachexia, the trial group was put under 160 mg per oral megestrol acetate bid plus 50 mg per oral thalidomide bid, whereas the patients in the control group were put only under megestrol acetate 50 mg per oral bid.[107] The trial group showed a significant increase from the baseline in body weight, appetite, QOL, and hand grip strength. A significant decrease was found in TNF-α and fatigue in this group. The trial group showed significantly higher mean changes in the endpoints from baseline than that of the control group. Therefore, the combination of megestrol acetate and thalidomide had greater impact in cancer cachexia than single agent megestrol acetate. Both the groups showed negligible toxicity.


  Psychosocial Consequences and their Intervention in Cancer Cachexia Top


Cancer patients face physical, psychological, social, and spiritual issues due to malnutrition.[108] The visible physical changes secondary to weight loss create emotional distress in cancer cachexia.[109],[110] The loss of weight in cancer cachexia being involuntary and fast paced raises fear of imminent death among the patients.[111],[112] The patients often stay recluse and get alienated from self as they feel uncomfortable meeting people due to disproportionate and severe bodily changes in them.[109],[113]As the patients feel unfamiliar toward their own body image, it ensues in feelings of helplessness, abandonment, and loss of control[113] and a sense of being stigmatized.[114] As the burden of cancer and associated cachexia affect patients social interactions and relationships, it is justified to think that the families of the patients are affected as well. The family members can influence both the psychosocial support and patient compliance toward the treatment, but the role of family members and their impact has mostly been side-lined. Many studies have been conducted to evaluate the role of psychoeducational protocols and their effect in supporting the needs of the patients and their families. Only few of them have provided evidence-based results.

The Macmillan Approach to Weight and Eating (MAWE) was administered by a trained clinical nurse specialist in a Phase II trial to check its deliverability, acceptability, and patient-perceived effect on weight-related distress (WRD) and eating-related distress (ERD).[115] The various elements of MAWE are breaking through weight loss taboo, narrating healing stories, managing conflict, support for self-action, and support for eating well. Elements suitable to the patient's WRD and ERD were administered during home visits between trained nurse, patient, and the care taker. The trial showed that MAWE is both deliverable and acceptable to the patients in clinical practice and more importantly can be administered by a specialist community care nurse experienced in palliative care.

A mixed method qualitative research study was used to develop a family-oriented psychosocial intervention for eating and weight-related issues in patients with incurable cancer.[116] The mode of interaction was through a face to face deliberation between patient, caretaker (family), and a trained nurse: Family Approach to Weight and Eating (FAWE). Its aim was to reinforce the patient and family caretaker coping resources to get through the involuntary weight loss and reduced appetite. The nurse researcher found FAWE both acceptable and deliverable. 15 out of 16 patients–caretaker dyads acknowledged the advantages of the approach, improving QOL at the end stage of life.

A randomized controlled pilot trial (conducted in Australia and Hong Kong) in advanced cancer patients and carers, with family-oriented psychosocial-based nutritional intervention although faced difficulty during recruitment and even though only half of the participants completed the final assessment, showed potential in certain patient outcomes.[117] There were improvements in ERD in both Australian and in Hong Kong data. In addition, eating-related enjoyment increased in Hong Kong data, whereas Australian data showed increase in QOL. On the contrary, the data on carer, i.e., ERD, anxiety, depression, and burden on caregiving showed little or no change.

A protocol for a single arm feasibility trial (NCT04153019) utilising psychoeducational and rehabilitative intervention to manage cancer cachexia patients, and their caregivers were published recently on March 01, 2021.[118] The study involves two components: (1) Psychoeducational intervention: Face to face discussions between cancer patients (30 in number), their caregivers and trained nurses to help the dyads to go through the stage of weight loss (involuntary) and to strengthen coping resources of dyads: (2) Rehabilitation intervention: Three biweekly educating discussions between the trained physical therapists and the dyads concentrating on self-management, goal-setting exercises (three home exercises/week). Currently recruiting, the rehabilitation intervention adds novelty to the study and allegedly was the only study of this type having both psychoeducational and rehabilitation (physiotherapy).


  Nursing Perspective Top


It is evident that the role of nursing staff becomes substantial during designing and administration of aforementioned studies and alike. Nurses deliver crucial psychological support to both the cancer patients and their families all along the course of the disease. Few of the activities that fall under the auspices of nursing practice include but not restricted to advice on nutrition, stress alleviation, management of associated symptoms, and reinforcing health-promoting behavior. All cancer patients probably interact with nurses more than they see other health-care workers including oncologists. This validates a convenient position for nurses to deliver support during prolonged care for the cachetic patients. As nutrition and exercise are strongholds of the multi-pronged treatment strategy in cancer cachexia, nurses ought to have ability in identifying and reporting cancer patients who are in need of additional nutritional supplements and physical activity. However, there has been a lack of training for nurses to tackle the issues of nutritional inadequacy and physical inaction in cancer patients; therefore, they might consider themselves lacking in knowledge for delivering advice on such patient issues. A few studies have shown that nurses do feel having less knowledge for advocating nutritional and physical activity issues in cancer patients. A web-based questionnaire study involving 355 oncology nurses providing advice on nutrition and 327 out of these providing physical activity advice showed that 43% felt having inadequate knowledge to give advice on nutrition and 46% thought they had less understanding to provide advice on physical activity.[119] However, nutritional advice is seen within the purview of nursing practice as indicated by abundant literature across the Western countries. As for example, North American Nursing Diagnosis Association considers nutrition as one among the 13 domains of nursing, practiced in the region.[120] Similarly, the Nursing and Midwifery Council of UK (regulatory body for nursing) acknowledges the pivotal role of nutrition for productive care of patients.

A number of studies reveal, nurses appreciating the role of nutrition to prevent and manage the progression of diseases,[121],[122] and appreciate nutritional care does fall under their jurisdiction.[123],[124],[125]

Limitations

This review is narrative and does not fulfil the criteria of a systematic study owing to the lack of methodological approaches.

The readers will have to refer to studies mentioned in this review to understand the methods employed and for any additional information as well.

Strengths

The compilation of the topics in the current review has been done in a streamlined fashion for easy comprehension.

The review attempts to put complete scale of issues including current advances in cancer cachexia in a concise fashion.


  Conclusions Top


Recent in-depth understanding of cancer cachexia has made it one of the most sought-after research fields. The advancements have allowed for apt understanding of the multiple factors that modulate the onset and development of this multisystem syndrome. Due to intricate mechanisms involved in cachexia, the development of a multimodal treatment protocol comprising of pharmacological agents, different exercise regimes, and nutritional supplements is necessary. More importantly, the role of palliative care nurses needs to be upgraded in view of their close association with cancer patients' right from the diagnosis until the treatment lasts. Adequate nutritional intervention is fundamental to prevent depleting muscle mass in cancer cachexia. Advanced cancer patients rely more on nurses for support than any other health-care personnel during their long hospitalization. A nurse can take an important role of assessing nutritional requirements of patients that could pave way for targeted nutritional prescriptions (through studies) to either inhibit or reduce muscle mass depletion during treatment and increase anabolic muscle processes during patient recovery. Such actions can result in compliance toward treatment, good prognosis, and improve overall survival.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Evans WJ, Morley JE, Argilés J, Bales C, Baracos V, Guttridge D, et al. Cachexia: A new definition. Clin Nutr 2008;27:793-9.  Back to cited text no. 1
    
2.
Morley JE, Anker SD, von Haehling S. Prevalence, incidence, and clinical impact of sarcopenia: Facts, numbers, and epidemiology-update 2014. J Cachexia Sarcopenia Muscle 2014;5:253-9.  Back to cited text no. 2
    
3.
von Haehling S, Anker MS, Anker SD. Prevalence and clinical impact of cachexia in chronic illness in Europe, USA, and Japan: Facts and numbers update 2016. J Cachexia Sarcopenia Muscle 2016;7:507-9.  Back to cited text no. 3
    
4.
Argilés JM, Busquets S, Stemmler B, López-Soriano FJ. Cancer cachexia: Understanding the molecular basis. Nat Rev Cancer 2014;14:754-62.  Back to cited text no. 4
    
5.
Martin L, Senesse P, Gioulbasanis I, Antoun S, Bozzetti F, Deans C, et al. Diagnostic criteria for the classification of cancer-associated weight loss. J Clin Oncol 2015;33:90-9.  Back to cited text no. 5
    
6.
Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, et al. Definition and classification of cancer cachexia: An international consensus. Lancet Oncol 2011;12:489-95.  Back to cited text no. 6
    
7.
Giordano A, Calvani M, Petillo O, Carteni' M, Melone MR, Peluso G. Skeletal muscle metabolism in physiology and in cancer disease. J Cell Biochem 2003;90:170-86.  Back to cited text no. 7
    
8.
Sadeghi M, Keshavarz-Fathi M, Baracos V, Arends J, Mahmoudi M, Rezaei N. Cancer cachexia: Diagnosis, assessment, and treatment. Crit Rev Oncol Hematol 2018;127:91-104.  Back to cited text no. 8
    
9.
Amano K, Maeda I, Morita T, Baba M, Miura T, Hama T, et al. C-reactive protein, symptoms and activity of daily living in patients with advanced cancer receiving palliative care. J Cachexia Sarcopenia Muscle 2017;8:457-65.  Back to cited text no. 9
    
10.
Fearon KC, Glass DJ, Guttridge DC. Cancer cachexia: Mediators, signaling, and metabolic pathways. Cell Metab 2012;16:153-66.  Back to cited text no. 10
    
11.
Ezeoke CC, Morley JE. Pathophysiology of anorexia in the cancer cachexia syndrome. J Cachexia Sarcopenia Muscle 2015;6:287-302.  Back to cited text no. 11
    
12.
Bruera E. ABC of palliative care. Anorexia, cachexia, and nutrition. BMJ 1997;315:1219-22.  Back to cited text no. 12
    
13.
Bennani-Baiti N, Walsh D. Animal models of the cancer anorexia-cachexia syndrome. Support Care Cancer 2011;19:1451-63.  Back to cited text no. 13
    
14.
Patel HJ, Patel BM. TNF-α and cancer cachexia: Molecular insights and clinical implications. Life Sci 2017;170:56-63.  Back to cited text no. 14
    
15.
Mantovani G, Maccio A, Mura L, Massa E, Mudu MC, Mulas C, et al. Serum levels of leptin and proinflammatory cytokines in patients with advanced-stage cancer at different sites. J Mol Med (Berl) 2000;78:554-61.  Back to cited text no. 15
    
16.
Tijerina AJ. The biochemical basis of metabolism in cancer cachexia. Dimens Crit Care Nurs 2004;23:237-43.  Back to cited text no. 16
    
17.
Bing C, Trayhurn P. Regulation of adipose tissue metabolism in cancer cachexia. Curr Opin Clin Nutr Metab Care 2008;11:201-7.  Back to cited text no. 17
    
18.
Li YP, Schwartz RJ, Waddell ID, Holloway BR, Reid MB. Skeletal muscle myocytes undergo protein loss and reactive oxygen-mediated NF-kappaB activation in response to tumor necrosis factor alpha. FASEB J 1998;12:871-80.  Back to cited text no. 18
    
19.
Porporato PE. Understanding cachexia as a cancer metabolism syndrome. Oncogenesis 2016;5:e200.  Back to cited text no. 19
    
20.
Aoyagi T, Terracina KP, Raza A, Matsubara H, Takabe K. Cancer cachexia, mechanism and treatment. World J Gastrointest Oncol 2015;7:17-29.  Back to cited text no. 20
    
21.
Laviano A, Meguid MM, Yang ZJ, Gleason JR, Cangiano C, Rossi Fanelli F. Cracking the riddle of cancer anorexia. Nutrition 1996;12:706-10.  Back to cited text no. 21
    
22.
Schmidt SF, Rohm M, Herzig S, Berriel Diaz M. Cancer cachexia: More than skeletal muscle wasting. Trends Cancer 2018;4:849-60.  Back to cited text no. 22
    
23.
Zaki MH, Nemeth JA, Trikha M. CNTO 328, a monoclonal antibody to IL-6, inhibits human tumor-induced cachexia in nude mice. Int J Cancer 2004;111:592-5.  Back to cited text no. 23
    
24.
Jatoi A, Ritter HL, Dueck A, Nguyen PL, Nikcevich DA, Luyun RF, et al. A placebo-controlled, double-blind trial of infliximab for cancer-associated weight loss in elderly and/or poor performance non-small cell lung cancer patients (N01C9). Lung Cancer 2010;68:234-9.  Back to cited text no. 24
    
25.
Barber MD, Fearon KC, Tisdale MJ, McMillan DC, Ross JA. Effect of a fish oil-enriched nutritional supplement on metabolic mediators in patients with pancreatic cancer cachexia. Nutr Cancer 2001;40:118-24.  Back to cited text no. 25
    
26.
Han Y, Weinman S, Boldogh I, Walker RK, Brasier AR. Tumor necrosis factoralpha-inducible IkappaBalpha proteolysis mediated by cytosolic m-calpain. A mechanism parallel to the ubiquitin-proteasome pathway for nuclear factorkappab activation. J Biol Chem 1999;274:787-94.  Back to cited text no. 26
    
27.
Jakubowski AA, Casper ES, Gabrilove JL, Templeton MA, Sherwin SA, Oettgen HF. Phase I trial of intramuscularly administered tumor necrosis factor in patients with advanced cancer. J Clin Oncol 1989;7:298-303.  Back to cited text no. 27
    
28.
Uehara A, Sekiya C, Takasugi Y, Namiki M, Arimura A. Anorexia induced by interleukin 1: Involvement of corticotropin-releasing factor. Am J Physiol 1989;257:R613-7.  Back to cited text no. 28
    
29.
Graziano F, Ruzzo A, Santini D, Humar B, Tonini G, Catalano V, et al. Prognostic role of interleukin-1beta gene and interleukin-1 receptor antagonist gene polymorphisms in patients with advanced gastric cancer. J Clin Oncol 2005;23:2339-45.  Back to cited text no. 29
    
30.
Kuroda K, Nakashima J, Kanao K, Kikuchi E, Miyajima A, Horiguchi Y, et al. Interleukin 6 is associated with cachexia in patients with prostate cancer. Urology 2007;69:113-7.  Back to cited text no. 30
    
31.
Mantovani G, Macciò A, Madeddu C, Serpe R, Massa E, Dessì M, et al. Randomized phase III clinical trial of five different arms of treatment in 332 patients with cancer cachexia. Oncologist 2010;15:200-11.  Back to cited text no. 31
    
32.
Baltgalvis KA, Berger FG, Pena MM, Davis JM, Muga SJ, Carson JA. Interleukin-6 and cachexia in ApcMin/+ mice. Am J Physiol Regul Integr Comp Physiol 2008;294:R393-401.  Back to cited text no. 32
    
33.
Petruzzelli M, Schweiger M, Schreiber R, Campos-Olivas R, Tsoli M, Allen J, et al. A switch from white to brown fat increases energy expenditure in cancer-associated cachexia. Cell Metab 2014;20:433-47.  Back to cited text no. 33
    
34.
von Haehling S, Morley JE, Anker SD. An overview of sarcopenia: Facts and numbers on prevalence and clinical impact. J Cachexia Sarcopenia Muscle 2010;1:129-33.  Back to cited text no. 34
    
35.
Martin L. Diagnostic criteria for cancer cachexia: Data versus dogma. Curr Opin Clin Nutr Metab Care 2016;19:188-98.  Back to cited text no. 35
    
36.
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES, National Institutes of Health, National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) v.4.03.2010 June 14.  Back to cited text no. 36
    
37.
Fearon KC, Voss AC, Hustead DS, Cancer Cachexia Study Group. Definition of cancer cachexia: Effect of weight loss, reduced food intake, and systemic inflammation on functional status and prognosis. Am J Clin Nutr 2006;83:1345-50.  Back to cited text no. 37
    
38.
Houten L, Reilley AA. An investigation of the cause of death from cancer. J Surg Oncol 1980;13:111-6.  Back to cited text no. 38
    
39.
Sun YS, Ye ZY, Qian ZY, Xu XD, Hu JF. Expression of TRAF6 and ubiquitin mRNA in skeletal muscle of gastric cancer patients. J Exp Clin Cancer Res 2012;31:81.  Back to cited text no. 39
    
40.
Bossola M, Muscaritoli M, Costelli P, Grieco G, Bonelli G, Pacelli F, et al. Increased muscle proteasome activity correlates with disease severity in gastric cancer patients. Ann Surg 2003;237:384-9.  Back to cited text no. 40
    
41.
Milan G, Romanello V, Pescatore F, Armani A, Paik JH, Frasson L, et al. Regulation of autophagy and the ubiquitin-proteasome system by the FoxO transcriptional network during muscle atrophy. Nat Commun 2015;6:6670.  Back to cited text no. 41
    
42.
Penna F, Costamagna D, Pin F, Camperi A, Fanzani A, Chiarpotto EM, et al. Autophagic degradation contributes to muscle wasting in cancer cachexia. Am J Pathol 2013;182:1367-78.  Back to cited text no. 42
    
43.
McClung JM, Judge AR, Powers SK, Yan Z. p38 MAPK links oxidative stress to autophagy-related gene expression in cachectic muscle wasting. Am J Physiol Cell Physiol 2010;298:C542-9.  Back to cited text no. 43
    
44.
Petruzzelli M, Wagner EF. Mechanisms of meta-bolic dysfunction in cancer-associated cachexia. Genes Dev 2016;30:489-501.  Back to cited text no. 44
    
45.
Op den Kamp CM, Langen RC, Snepvangers FJ, de Theije CC, Schellekens JM, Laugs F, et al. Nuclear transcription factor κ B activation and protein turnover adaptations in skeletal muscle of patients with progressive stages of lung cancer cachexia. Am J Clin Nutr 2013;98:738-48.  Back to cited text no. 45
    
46.
Boyer-Guittaut M, Poillet L, Liang Q, Bôle-Richard E, Ouyang X, Benavides GA, et al. The role of GABARAPL1/GEC1 in autophagic flux and mitochondrial quality control in MDA-MB-436 breast cancer cells. Autophagy 2014;10:986-1003.  Back to cited text no. 46
    
47.
Costelli P, Reffo P, Penna F, Autelli R, Bonelli G, Baccino FM. Ca(2+)-dependent proteolysis in muscle wasting. Int J Biochem Cell Biol 2005;37:2134-46.  Back to cited text no. 47
    
48.
Baracos VE, DeVivo C, Hoyle DH, Goldberg AL. Activation of the ATP-ubiquitinproteasome pathway in skeletal muscle of cachectic rats bearing a hepatoma. Am J Physiol 1995;268:E996-1006.  Back to cited text no. 48
    
49.
Fearon K, Arends J, Baracos V. Understanding the mechanisms and treatment options in cancer cachexia. Nat Rev Clin Oncol 2013;10:90-9.  Back to cited text no. 49
    
50.
Argilés JM, López-Soriano FJ, Stemmler B, Busquets S. Novel targeted therapies for cancer cachexia. Biochem J 2017;474:2663-78.  Back to cited text no. 50
    
51.
Aversa Z, Costelli P, Muscaritoli M. Cancer-induced muscle wasting: Latest findings in prevention and treatment. Ther Adv Med Oncol 2017;9:369-82.  Back to cited text no. 51
    
52.
Fearon KC, Von Meyenfeldt MF, Moses AG, Van Geenen R, Roy A, Gouma DJ, et al. Effect of a protein and energy dense N-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: A randomised double blind trial. Gut 2003;52:1479-86.  Back to cited text no. 52
    
53.
Aversa Z, Bonetto A, Costelli P, Minero VG, Penna F, Baccino FM, et al. β-hydroxy-β-methylbutyrate (HMB) attenuates muscle and body weight loss in experimental cancer cachexia. Int J Oncol 2011;38:713-20.  Back to cited text no. 53
    
54.
Fitschen PJ, Wilson GJ, Wilson JM, Wilund KR. Efficacy of β-hydroxy-β-methylbutyrate supplementation in elderly and clinical populations. Nutrition 2013;29:29-36.  Back to cited text no. 54
    
55.
Murphy RA, Mourtzakis M, Chu QS, Baracos VE, Reiman T, Mazurak VC. Nutritional intervention with fish oil provides a benefit over standard of care for weight and skeletal muscle mass in patients with nonsmall cell lung cancer receiving chemotherapy. Cancer 2011;117:1775-82.  Back to cited text no. 55
    
56.
Sánchez-Lara K, Turcott JG, Juárez-Hernández E, Nuñez-Valencia C, Villanueva G, Guevara P, et al. Effects of an oral nutritional supplement containing eicosapentaenoic acid on nutritional and clinical outcomes in patients with advanced non-small cell lung cancer: Randomised trial. Clin Nutr 2014;33:1017-23.  Back to cited text no. 56
    
57.
Gramignano G, Lusso MR, Madeddu C, Massa E, Serpe R, Deiana L, et al. Efficacy of l-carnitine administration on fatigue, nutritional status, oxidative stress, and related quality of life in 12 advanced cancer patients undergoing anticancer therapy. Nutrition 2006;22:136-45.  Back to cited text no. 57
    
58.
Kraft M, Kraft K, Gärtner S, Mayerle J, Simon P, Weber E, et al. L-Carnitine-supplementation in advanced pancreatic cancer (CARPAN) – A randomized multicentre trial. Nutr J 2012;11:52.  Back to cited text no. 58
    
59.
Arends J, Bachmann P, Baracos V, Barthelemy N, Bertz H, Bozzetti F, et al. ESPEN guidelines on nutrition in cancer patients. Clin Nutr 2017;36:11-48.  Back to cited text no. 59
    
60.
Bruera E, Strasser F, Palmer JL, Willey J, Calder K, Amyotte G, et al. Effect of fish oil on appetite and other symptoms in patients with advanced cancer and anorexia/cachexia: A double-blind, placebo-controlled study. J Clin Oncol 2003;21:129-34.  Back to cited text no. 60
    
61.
Dewey A, Baughan C, Dean T, Higgins B, Johnson I. Eicosapentaenoic acid (EPA, an omega-3 fatty acid from fish oils) for the treatment of cancer cachexia. Cochrane Database Syst Rev 2007;2007:CD004597.  Back to cited text no. 61
    
62.
Mazzotta P, Jeney CM. Anorexia-cachexia syndrome: A systematic review of the role of dietary polyunsaturated Fatty acids in the management of symptoms, survival, and quality of life. J Pain Symptom Manage 2009;37:1069-77.  Back to cited text no. 62
    
63.
van der Meij BS, Langius JA, Smit EF, Spreeuwenberg MD, von Blomberg BM, Heijboer AC, et al. Oral nutritional supplements containing (n-3) polyunsaturated fatty acids affect the nutritional status of patients with stage III non-small cell lung cancer during multimodality treatment. J Nutr 2010;140:1774-80.  Back to cited text no. 63
    
64.
Weed HG, Ferguson ML, Gaff RL, Hustead DS, Nelson JL, Voss AC. Lean body mass gain in patients with head and neck squamous cell cancer treated perioperatively with a protein- and energy-dense nutritional supplement containing eicosapentaenoic acid. Head Neck 2011;33:1027-33.  Back to cited text no. 64
    
65.
Cotogni P. Enteral versus parenteral nutrition in cancer patients: Evidences and controversies. Ann Palliat Med 2016;5:42-9.  Back to cited text no. 65
    
66.
Jatoi A, Dakhil SR, Nguyen PL, Sloan JA, Kugler JW, Rowland KM Jr, et al. A placebo-controlled double blind trial of etanercept for the cancer anorexia/weight loss syndrome: Results from N00C1 from the North Central Cancer Treatment Group. Cancer 2007;110:1396-403.  Back to cited text no. 66
    
67.
Gordon JN, Trebble TM, Ellis RD, Duncan HD, Johns T, Goggin PM. Thalidomide in the treatment of cancer cachexia: A randomised placebo controlled trial. Gut 2005;54:540-5.  Back to cited text no. 67
    
68.
Mantovani G. Randomised phase III clinical trial of 5 different arms of treatment on 332 patients with cancer cachexia. Eur Rev Med Pharmacol Sci 2010;14:292-301.  Back to cited text no. 68
    
69.
Yennurajalingam S, Willey JS, Palmer JL, Allo J, Del Fabbro E, Cohen EN, et al. The role of thalidomide and placebo for the treatment of cancer-related anorexia-cachexia symptoms: Results of a double-blind placebo-controlled randomized study. J Palliat Med 2012;15:1059-64.  Back to cited text no. 69
    
70.
Mehrzad V, Afshar R, Akbari M. Pentoxifylline treatment in patients with cancer cachexia: A double-blind, randomized, placebo-controlled clinical trial. Adv Biomed Res 2016;5:60.  Back to cited text no. 70
[PUBMED]  [Full text]  
71.
Goldberg RM, Loprinzi CL, Mailliard JA, O'Fallon JR, Krook JE, Ghosh C, et al. Pentoxifylline for treatment of cancer anorexia and cachexia? A randomized, double-blind, placebo-controlled trial. J Clin Oncol 1995;13:2856-9.  Back to cited text no. 71
    
72.
Clarke SJ, Smith JT, Gebbie C, Sweeney C, Olszewski N. A phase I, pharmacokinetic. (PK), and preliminary efficacy assessment of ALD518, a humanized anti-IL-6 antibody, in patients with advanced cancer. J Clin Oncol 2009;27:3025.  Back to cited text no. 72
    
73.
Rigas JR, Schuster M, Orlov SV, Milovanovic B, Prabhash K, Smith JT, et al. Efect of ALD518, a humanized anti-IL-6 antibody, on lean body mass loss and symptoms in patients with advanced non-small cell lungcancer. (NSCLC): Results of a phase II randomized, double-blind safety and efficacy trial. J Clin Oncol 2010;28:7622.  Back to cited text no. 73
    
74.
Hong DS, Hui D, Bruera E, Janku F, Naing A, Falchook GS, et al. MABp1, a first-in-class true human antibody targeting interleukin-1a in refractory cancers: An open-label, phase 1 dose-escalation and expansion study. Lancet Oncol 2014;15:656-66.  Back to cited text no. 74
    
75.
Hickish T, Andre T, Wyrwicz L, Saunders M, Sarosiek T, Kocsis J, et al. MABp1 as a novel antibody treatment for advanced colorectal cancer: A randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol 2017;18:192-201.  Back to cited text no. 75
    
76.
Madeddu C, Dessì M, Panzone F, Serpe R, Antoni G, Cau MC, et al. Randomized phase III clinical trial of a combined treatment with carnitine + celecoxib ± megestrol acetate for patients with cancer-related anorexia/cachexia syndrome. Clin Nutr 2012;31:176-82.  Back to cited text no. 76
    
77.
Lundholm K, Gunnebo L, Körner U, Iresjö BM, Engström C, Hyltander A, et al. Effects by daily long term provision of ghrelin to unselected weight-losing cancer patients: A randomized double-blind study. Cancer 2010;116:2044-52.  Back to cited text no. 77
    
78.
Hiura Y, Takiguchi S, Yamamoto K, Takahashi T, Kurokawa Y, Yamasaki M, et al. Effects of ghrelin administration during chemotherapy with advanced esophageal cancer patients: A prospective, randomized, placebo-controlled phase 2 study. Cancer 2012;118:4785-94.  Back to cited text no. 78
    
79.
Marceca GP, Londhe P, Calore F. Management of cancer cachexia: Attempting to develop new pharmacological agents for new effective therapeutic options. Front Oncol 2020;10:298.  Back to cited text no. 79
    
80.
Khatib MN, Gaidhane A, Gaidhane S, Quazi ZS. Ghrelin as a promising therapeutic option for cancer cachexia. Cell Physiol Biochem 2018;48:2172-88.  Back to cited text no. 80
    
81.
Ali S, Chen JA, Garcia JM. Clinical development of ghrelin axis-derived molecules for cancer cachexia treatment. Curr Opin Support Palliat Care 2013;7:368-75.  Back to cited text no. 81
    
82.
Bednarek MA, Feighner SD, Pong SS, McKee KK, Hreniuk DL, Silva MV, et al. Structure-function studies on the new growth hormone-releasing peptide, ghrelin: Minimal sequence of ghrelin necessary for activation of growth hormone secretagogue receptor 1a. J Med Chem 2000;43:4370-6.  Back to cited text no. 82
    
83.
Garcia JM, Polvino WJ. Effect on body weight and safety of RC-1291, a novel, orally available ghrelin mimetic and growth hormone secretagogue: Results of a phase I, randomized, placebo-controlled, multiple-dose study in healthy volunteers. Oncologist 2007;12:594-600.  Back to cited text no. 83
    
84.
Temel JS, Abernethy AP, Currow DC, Friend J, Duus EM, Yan Y, et al. Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): Results from two randomised, double-blind, phase 3 trials. Lancet Oncol 2016;17:519-31.  Back to cited text no. 84
    
85.
Currow D, Temel JS, Abernethy A, Milanowski J, Friend J, Fearon KC. ROMANA 3: A phase 3 safety extension study of anamorelin in advanced non-small-cell lung cancer (NSCLC) patients with cachexia. Ann Oncol 2017;28:1949-56.  Back to cited text no. 85
    
86.
Katakami N, Uchino J, Yokoyama T, Naito T, Kondo M, Yamada K, et al. Anamorelin (ONO-7643) for the treatment of patients with non-small cell lung cancer and cachexia: Results from a randomized, double- blind, placebo-controlled, multicentre study of Japanese patients (ONO-7643-04). Cancer 2018;124:606-16.  Back to cited text no. 86
    
87.
Hamauchi S, Furuse J, Takano T, Munemoto Y, Furuya K, Baba H, et al. A multicenter, open-label, single-arm study of anamorelin (ONO-7643) in advanced gastrointestinal cancer patients with cancer cachexia. Cancer 2019;125:4294-302.  Back to cited text no. 87
    
88.
Wakabayashi H, Arai H, Inui A. The regulatory approval of anamorelin for treatment of cachexia in patients with non-small cell lung cancer, gastric cancer, pancreatic cancer, and colorectal cancer in Japan: Facts and numbers. J Cachexia Sarcopenia Muscle 2021;12:14-6.  Back to cited text no. 88
    
89.
Ruiz Garcia V, López-Briz E, Carbonell Sanchis R, Gonzalvez Perales JL, Bort-Marti S. Megestrol acetate for treatment of anorexia-cachexia syndrome. Cochrane Database Syst Rev 2013;2013:CD004310.  Back to cited text no. 89
    
90.
Mantovani G, Macciò A, Lai P, Massa E, Ghiani M, Santona MC. Cytokine involvement in cancer anorexia/cachexia: Role of megestrol acetate and medroxyprogesterone acetate on cytokine downregulation and improvement of clinical symptoms. Crit Rev Oncog 1998;9:99-106.  Back to cited text no. 90
    
91.
Yeh SS, Wu SY, Levine DM, Parker TS, Olson JS, Stevens MR, et al. The correlation of cytokine levels with body weight after megestrol acetate treatment in geriatric patients. J Gerontol A Biol Sci Med Sci 2001;56:M48-54.  Back to cited text no. 91
    
92.
Madeddu C, Macciò A, Panzone F, Tanca FM, Mantovani G. Medroxyprogesterone acetate in the management of cancer cachexia. Expert Opin Pharmacother 2009;10:1359-66.  Back to cited text no. 92
    
93.
Tuca A, Jimenez-Fonseca P, Gascón P. Clinical evaluation and optimal management of cancer cachexia. Crit Rev Oncol Hematol 2013;88:625-36.  Back to cited text no. 93
    
94.
Mantovani G, Madeddu C. Cancer cachexia: Medical management. Support Care Cancer 2010;18:1-9.  Back to cited text no. 94
    
95.
Loprinzi CL, Kugler JW, Sloan JA, Mailliard JA, Krook JE, Wilwerding MB, et al. Randomized comparison of megestrol acetate versus dexamethasone versus fluoxymesterone for the treatment of cancer anorexia/cachexia. J Clin Oncol 1999;17:3299-306.  Back to cited text no. 95
    
96.
Lai V, George J, Richey L, Kim HJ, Cannon T, Shores C, et al. Results of a pilot study of the effects of celecoxib on cancer cachexia in patients with cancer of the head, neck, and gastrointestinal tract. Head Neck 2008;30:67-74.  Back to cited text no. 96
    
97.
Mantovani G, Macciò A, Madeddu C, Serpe R, Antoni G, Massa E, et al. Phase II nonrandomized study of the efficacy and safety of COX-2 inhibitor celecoxib on patients with cancer cachexia. J Mol Med (Berl) 2010;88:85-92.  Back to cited text no. 97
    
98.
Reid J, Hughes CM, Murray LJ, Parsons C, Cantwell MM. Non-steroidal anti-inflammatory drugs for the treatment of cancer cachexia: A systematic review. Palliat Med 2013;27:295-303.  Back to cited text no. 98
    
99.
Solheim TS, Fearon KC, Blum D, Kaasa S. Non-steroidal anti-inflammatory treatment in cancer cachexia: A systematic literature review. Acta Oncol 2013;52:6-17.  Back to cited text no. 99
    
100.
Wang J, Wang Y, Tong M, Pan H, Li D. New Prospect for Cancer Cachexia: Medical Cannabinoid. J Cancer 2019;10:716-20.  Back to cited text no. 100
    
101.
Cannabis-In-Cachexia-Study-Group. Strasser F, Luftner D, Possinger K, Ernst G, Ruhstaller T, et al. Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: A multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group. J Clin Oncol 2006;24:3394-400.  Back to cited text no. 101
    
102.
Brisbois TD, de Kock IH, Watanabe SM, Mirhosseini M, Lamoureux DC, Chasen M, et al. Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: Results of a randomized, double-blind, placebo-controlled pilot trial. Ann Oncol 2011;22:2086-93.  Back to cited text no. 102
    
103.
Bar-Sela G, Zalman D, Semenysty V, Ballan E. The effects of dosage-controlled cannabis capsules on cancer-related cachexia and anorexia syndrome in advanced cancer patients: Pilot study. Integr Cancer Ther 2019;18:1-8.  Back to cited text no. 103
    
104.
McKeaveney C, Maxwell P, Noble H, Reid J. A critical review of multimodal interventions for cachexia. Adv Nutr 2021;12:523-32.  Back to cited text no. 104
    
105.
Solheim TS, Laird BJA, Balstad TR, Stene GB, Bye A, Johns N, et al. A randomized phase II feasibility trial of a multimodal intervention for the management of cachexia in lung and pancreatic cancer. J Cachexia Sarcopenia Muscle 2017;8:778-88.  Back to cited text no. 105
    
106.
Uster A, Ruehlin M, Mey S, Gisi D, Knols R, Imoberdorf R, et al. Effects of nutrition and physical exercise intervention in palliative cancer patients: A randomized controlled trial. Clin Nutr 2018;37:1202-9.  Back to cited text no. 106
    
107.
Wen HS, Li X, Cao YZ, Zhang CC, Yang F, Shi YM, et al. Clinical studies on the treatment of cancer cachexia with megestrol acetate plus thalidomide. Chemotherapy 2012;58:461-7.  Back to cited text no. 107
    
108.
Cooper C, Burden ST, Cheng H, Molassiotis A. Understanding and managing cancer-related weight loss and anorexia: Insights from a systematic review of qualitative research. J Cachexia Sarcopenia Muscle 2015;6:99-111.  Back to cited text no. 108
    
109.
Reid J, McKenna H, Fitzsimons D, McCance T. The experience of cancer cachexia: A qualitative study of advanced cancer patients and their family members. Int J Nurs Stud 2009;46:606-16.  Back to cited text no. 109
    
110.
Amano K, Maeda I, Morita T, Okajima Y, Hama T, Aoyama M, et al. Eating-related distress and need for nutritional support of families of advanced cancer patients: A nationwide survey of bereaved family members. J Cachexia Sarcopenia Muscle 2016;7:527-34.  Back to cited text no. 110
    
111.
Hopkinson JB. Psychosocial impact of cancer cachexia. J Cachexia Sarcopenia Muscle 2014;5:89-94.  Back to cited text no. 111
    
112.
Reid J, McKenna HP, Fitzsimons D, McCance TV. An exploration of the experience of cancer cachexia: What patients and their families want from healthcare professionals. Eur J Cancer Care (Engl) 2010;19:682-9.  Back to cited text no. 112
    
113.
Hopkinson J, Wright D, Corner J. Exploring the experience of weight loss in people with advanced cancer. J Adv Nurs 2006;54:304-12.  Back to cited text no. 113
    
114.
McClement S. Involuntary weight loss and altered body image in patients with cancer anorexia-cachexia syndrome. In: Del Fabbro EB, Baracos V, Bowling T, Demark-Wahnefried W, Hopkinson J, editors. Nutrition and the Cancer Patient. Oxford: Oxford University Press; 2010. p. 471-6.  Back to cited text no. 114
    
115.
Hopkinson JB, Fenlon DR, Okamoto I, Wright DN, Scott I, Addington-Hall JM, et al. The deliverability, acceptability, and perceived effect of the Macmillan approach to weight loss and eating difficulties: A phase II, cluster-randomized, exploratory trial of a psychosocial intervention for weight- and eating-related distress in people with advanced cancer. J Pain Symptom Manage 2010;40:684-95.  Back to cited text no. 115
    
116.
Hopkinson JB, Richardson A. A mixed-methods qualitative research study to develop a complex intervention for weight loss and anorexia in advanced cancer: The Family Approach to Weight and Eating. Palliat Med 2015;29:164-76.  Back to cited text no. 116
    
117.
Molassiotis A, Brown T, Cheng HL, Byrnes A, Chan RJ, Wyld D, et al. The effects of a family-centered psychosocial-based nutrition intervention in patients with advanced cancer: The PiCNIC2 pilot randomised controlled trial. Nutr J 2021;20:2.  Back to cited text no. 117
    
118.
Buonaccorso L, Bertocchi E, Autelitano C, Allisen Accogli M, Denti M, Fugazzaro S, et al. Psychoeducational and rehabilitative intervention to manage cancer cachexia (PRICC) for patients and their caregivers: Protocol for a single-arm feasibility trial. BMJ Open 2021;11:e042883.  Back to cited text no. 118
    
119.
van Veen MR, Hoedjes M, Versteegen JJ, van de Meulengraaf-Wilhelm N, Kampman E, Beijer S. Improving Oncology Nurses' Knowledge About Nutrition and Physical Activity for Cancer Survivors. Oncol Nurs Forum 2017;44:488-96.  Back to cited text no. 119
    
120.
Herdman T. NANDA International Nursing Diagnoses: Definitions and Classification, 2012–2014. Oxford, UK: Wiley Blackwell; 2012.  Back to cited text no. 120
    
121.
Cass S, Ball L, Leveritt M. Australian practice nurses' perceptions of their role and competency to provide nutrition care to patients living with chronic disease. Aust J Prim Health 2014;20:203-8.  Back to cited text no. 121
    
122.
Yalcin N, Cihan A, Gundogdu H, Ocakci A. Nutrition knowledge level of nurses. Health Sci J 2013;7:100-8.  Back to cited text no. 122
    
123.
Green SM, James EP, Latter S, Sutcliffe M, Fader MJ. Barriers and facilitators to screening for malnutrition by community nurses: A qualitative study. J Hum Nutr Diet 2014;27:88-95.  Back to cited text no. 123
    
124.
Pedersen PU, Tewes M, Bjerrum M. Implementing nutritional guidelines – The effect of systematic training for nurse nutrition practitioners. Scand J Caring Sci 2012;26:178-85.  Back to cited text no. 124
    
125.
Martin L, Leveritt MD, Desbrow B, Ball LE. The self-perceived knowledge, skills and attitudes of Australian practice nurses in providing nutrition care to patients with chronic disease. Fam Pract 2014;31:201-8.  Back to cited text no. 125
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Pathogenesis
Diagnosis of Can...
Skeletal Muscle ...
Treatment of Can...
Existing pharmac...
Psychosocial Con...
Nursing Perspective
Conclusions
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed866    
    Printed2    
    Emailed0    
    PDF Downloaded54    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]