Cancer cachexia is a devastating syndrome of advanced malignancy which negatively impacts on patients’ morbidity, mortality and quality of life. Chronic inflammation is a key characteristic of cancer cachexia. Therefore, non-steroidal anti-inflammatory drugs (NSAIDs) may be able to break the cycle of cachexia.
Aim:
To systematically review the literature on the use of NSAIDs for the treatment of cachexia in advanced cancer patients.
Design:
All titles retrieved through searching were downloaded to a reference management database, duplicates were removed and the remaining citations were checked for eligibility. Full copies of all eligible articles were obtained and reviewed.
Data sources:
Electronic searches (from inception up to 09/2011) included CINAHL, MEDLINE, EMBASE, and Web of Science. Reference lists from reviewed articles, trial registers and abstracts from relevant conferences were searched. Eligibility criteria were (a) Randomised Controlled Trial; (b) participants were adults with cancer with weight loss or a clinical diagnosis of cachexia; (c) administration of oral NSAIDs.
Results:
Four studies were included. These studies provided some evidence of positive therapeutic effect on quality of life, performance status, inflammatory markers, weight gain and survival, but there was insufficient evidence demonstrated for their widespread use in practice.
Conclusions:
Insufficient studies have been performed to allow a conclusion to be formed with regard to the effectiveness of NSAIDs in the treatment of cachexia in advanced cancer. Major challenges in this patient cohort include the lack of uniformity of inclusion criteria across studies and the frailty of the patients recruited.
FearonKStrasserFBosaeusI. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol2011; 12: 489–495.
2.
TisdaleMJ. Mechanisms of cancer cachexia. Physiol Rev2009; 89(2): 381–410.
3.
DunlopR. Clinical epidemiology of cancer cachexia. In: BrueraEHigginsonIJ (eds) Cachexia-Anorexia in Cancer Patients. Oxford: Oxford University Press, 1996, pp. 76–82.
4.
BurckartKBecaSUrbanRJ. Pathogenesis of muscle wasting in cancer cachexia: targeted anabolic and anticatabolic therapies. Curr Opin Clin Nutr Metab Care2010; 13(4): 410–416
5.
ReidJMcKennaHFitzsimonsD. The experience of cancer cachexia: a qualitative study of advanced cancer patients and their family members. Int J Nurs Stud2009; 46(5): 606–616.
6.
GordonJNTrebbleTMEllisRD. Thalidomide in the treatment of cancer cachexia: a randomised placebo controlled trial. Gut2005; 54(4): 540–545.
7.
MantovaniGMaccioAMadedduC. Randomised phase III clinical trial of five different arms of treatment in 332 patients with cancer cachexia. The Oncologist2010; 15: 200–211.
8.
McMillanDCLeenESmithJ. Effect of extended ibuprofen administration on cortisol, interleukin-6 and the acute phase protein response in colorectal cancer patients. Eur J Surg Oncol1995; 21: 531–534.
9.
PrestonTFearonKCHMcMillanDC. Effect of ibuprofen on the acute-phase response and protein metabolism in patients with cancer and weight loss. Br J Surg199; 82(2): 229–234.
10.
MaddocksMByrneAJohnsonCD. Physical activity level as an outcome measure for use in cancer cachexia trials: a feasibility study. Support Care Cancer2010; 18(12): 1539–1544.
11.
RadbruchLElsnerFTrottenbergP. Clinical practice guidelines on cancer cachexia in advanced cancer patients. Aachen, Department of Palliative Medicine/European Palliative Care Research Collaborative; 2010.
12.
MillarCReidJPorterS. Providing care for palliative cancer patients who have cachexia: are we meeting the challenge?Cancer Nursing Practice2009; 8(4): 24–27.
13.
BerensteinGOrtizZ. Megestrol acetate for treatment of anorexia-cachexia syndrome. Cochrane Database of Systematic Reviews2005; 2.
14.
DeweyABaughanCDeanTP. Eicosapentaenoic acid (EPA, an omega-3 fatty acid from fish oils) for the treatment of cancer cachexia. Cochrane Database of Systematic Reviews2007; 1.
15.
MantovaniGMacciòAMadedduC. A phase II study with antioxidants, both in the diet and supplemented, pharmaconutritional support, progestagen, and anti-cyclooxygenase-2 showing efficacy and safety in patients with cancer-related anorexia/cachexia and oxidative stress. Cancer Epidemiol Biomarkers Prev. 2006; 15(5): 1030–4.
16.
CercheittiCLNaviganteAHPeluffoGDDiamentMJStillitaniIKleinSACabalarME. Effects of celecoxib, medroxyprogesterone, and dietary intervention on systemic syndromes in patients with advanced lung adenocarcinoma: a pilot study. J Pain Symptom Manage2004; 27(1): 85–95.
17.
LundholmKDanerydPBosaeusIKornerULindholmE. Palliative nutritional intervention in addition to cyclooxygenase and erythropoietin treatment for patients with malignant disease: Effects on survival, metabolism, and function. Cancer2004; 100 (9): 1967–1977.
18.
LundholmKDanerydPKornerUHyltanderABosaeusI. Evidence that long-term COX-treatment improves energy homeostasis and body composition in cancer patients with progressive cachexia. Int J Oncol2004; 24(3): 505–512.
19.
McMillanDCO’GormanPFearonKCHMcArdleCS. A pilot study of megestrol acetate and ibuprofen in the treatment of cachexia in gastrointestinal cancerpatients. Cancer Research Campaign1997; 76: 788–790.
20.
WigmoreSJFalconerJSPlesterCERossJAMaingayJPCarterDCFearonKCH. Ibuprofen reduces energy expenditure and acute-phase protein production compared with placebo in pancreatic cancer patients. Br J Cancer1995; 72(1): 185–188.
21.
JadadARMooreRACarrollD. Assessing the quality of reports of randomized clinical trials: is blinding necessary?Contr Clin Trials1996; 17: 1–12.
22.
TuechJJ. Methodological Quality and Reporting of Ethical Requirements in Phase III Cancer Trials. J Med Ethics2005; 31(5): 251–255.
23.
LaiVGeorgeJRicheyLKimHJCannonTShoresCCouchM. 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 and Neck, 2008; 30(1): 67–74.
24.
McMillanDCWigmoreSJFearonKCO’GormanPWrightCEMcArdleCS. A prospective randomized study of megestrol acetate and ibuprofen in gastrointestinal cancer patients with weight loss. Br J Cancer1999; 79(3-4): 495–500.
25.
CerchiettiLCNaviganteAHCastroMA. Effects of eicosapentaenoic and docosahexaenoic n-3 fatty acids from fish oil and preferential Cox-2 inhibition on systemic syndromes in patients with advanced lung cancer. Nutr Canc2007; 59(1): 14–20.
26.
LundholmKGelinJHyltanderALönnrothCSandströmRSvaningerGKörnerUGülichMKärreforsINorliB. Anti-inflammatory treatment may prolong survival in undernourished patients with metastatic solid tumors. Canc Res1994; 54(21): 5602–6.
ReidJDonnellyMCantwellMCardwellCRMillsMMurrayLJ. Thalidomide for managing cancer cachexia (Protocol). Cochrane Database of Systematic Reviews. 2010: 9 DOI: 10.1002/14651858.CD008664.
29.
MacDonaldN. Cancer cachexia and targeting chronic inflammation: A unified approach to cancer treatment and palliative/supportive care. Support Oncol2007; 5(4): 157–162.
30.
MuscaritoliMBossolaMAversaZBellantonebRFanelliaFP. Prevention and treatment of cancer cachexia: New insights into an old problem. Eur J Canc2006; 42(6): 31–41.31.
31.
FearonKCH. Cancer cachexia: Developing multimodal therapy for a multidimensional problem. Eur J Canc2008; 44: 1124–1132.
32.
MuscaritoliMAnkerSDArgilesJAversaZBauerJMBioloG. Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by Special Interest Groups (SIG) “cachexia–anorexia in chronic wasting diseases” and “nutrition in geriatrics”Clin Nutr2010; 29: 154–9.
33.
DaheleMFearonKCH. Research methodology: cancer cachexia syndrome. Palliat Med2004; 18(5): 409–417.
34.
RyanCGGrantPMTigbeWWGranatMH. The validity and reliability of a novel activity monitor as a measure of walking. Br J Sports Med2006; 40(9): 779–84.
35.
GrantMDPMitchellSGranatM. Activity-monitor accuracy in measuring step number and cadence in community-dwelling older adults. J Aging Phys Activ2008; 16(2): 201–14.
36.
MaddocksMByrneAJohnsonCDWilsonRHFearonKCWilcockA. Physical activity level as an outcome measure for use in cancer cachexia trials: a feasibility study. Support Care Canc2010; 18: 1539–44.
