Cancer-related Anorexia-cachexia Syndrome Research Articles

The efficacy and safety of anamorelin for patients with cancer-related anorexia/cachexia syndrome: a systematic review and meta-analysis

Cancer-related anorexia/cachexia syndrome (CACS) is characterized by anorexia and loss of body weight. Evidence is insufficient to strongly endorse any pharmacologic agent for the treatment of CACS. In this systematic review, we assessed the efficacy of oral anamorelin treatment for patients with CACS. On July 6, 2022, we systematically searched the following databases for randomized controlled trials (RCTs) of adults with CACS comparing oral anamorelin versus placebo: CENTRAL, PubMed, EMBASE, and ICHUSHI. The primary outcomes were total body weight (TBW), patient-reported quality of life (QOL), and adverse events (AEs). Secondary outcomes included lean body mass (LBM), overall survival (OS), non-dominant hand grip strength (HGS), and appetite. We included seven RCTs with a total of 1944 CACS patients. Anamorelin significantly increased TBW (mean difference (MD) 1.73, 95% confidence interval (CI) 1.34–2.13, p < 0.00001), LBM (MD 1.06, 95% CI 0.30–1.81, p = 0.006), and QOL (standardized mean difference (SMD) 0.16, 95% CI 0.04–0.27, p = 0.006) compared with placebo without a significant difference in all AEs, severe AEs, OS, HGS or appetite. Anamorelin may be an effective treatment for CACS patients; however, further studies are needed to confirm the efficacy and safety of this drug.

Mirtazapine versus Megestrol in the Treatment of Anorexia-Cachexia Syndrome in Patients with Advanced Cancer: A Randomized, Double-Blind, Controlled Phase II Clinical Trial.

This study compared mirtazapine with megestrol in the management of cancer-related anorexia-cachexia syndrome in patients with advanced cancer. A randomized, double-blind, controlled clinical trial involving patients with advanced cancer and anorexia-cachexia syndrome was performed. Participants received mirtazapine 30 mg/day or megestrol 320 mg/day for eight weeks. The primary endpoint was the effect of mirtazapine on weight gain and the secondary endpoints were its effect on appetite, muscle strength, physical performance, body composition, adverse events, and medication adherence. Linear regression model with mixed effects was applied and a significance level of 5% was adopted. Fifty-two patients were randomized. Mean age was 65.8 ± 8.4 years. There was weight gain in 52% of the participants in the megestrol group and in 38% in the mirtazapine group after four weeks (p = 0.040). Appetite improved in 92% of the participants in the megestrol group and in 56% in the mirtazapine group after eight weeks (p = 0.007). In the sub-analysis by sex, women showed improvement in appetite (p < 0.001) and weight gain (p < 0.005) in the mirtazapine group, which was not observed in men. Mirtazapine appears to be inferior to megestrol in weight and appetite improvement. However, there may be a difference in the therapeutic response between sexes.

Weight gain as a surrogate marker of longer survival in advanced non-small cell lung cancer patients.

Weight loss (WL), as a key step of the irreversible and fatal cancer-related anorexia cachexia syndrome is present to some degree in 80% of non-small cell lung cancer (NSCLC) patients upon diagnosis which has been clearly proved to negatively alter patients' performance status, quality of life (QOL), response to treatment, and prognosis. However, WL is not a problem encountered only upon diagnosis but is also commonly reported during the course of aggressive chemotherapy, radiotherapy (RT) and particularly the concurrent chemoradiotherapy (C-CRT) which may further diminish QOL measures and clinical outcomes. In general, the NSCLC literature has concentrated on WL during the treatment course, but recent studies have demonstrated that it is possible to preserve or even experience weight gain (WG) during or just short after the discontinuation of various cancer treatments in approximately 40% to 45% NSCLC patients. Considering the fact that recent evidence suggest a prognostic and predictive role for WG in anticipation of longer survival times and better response rates in weight gainers, this current manuscript will specifically aim to realize the actual value of WG in locally advanced and metastatic NSCLC patients which may potentially be added to the conventional prognostic and predictive factors as a novel surrogate marker of outcomes in such patients.

Assessment of nutritional and inflammatory status to determine the prevalence of malnutrition in patients undergoing surgery for colorectal carcinoma.

e15091Background: Cancer disease is often associated with protein-caloric malnutrition that affects 8% to 84% of patients. Cancer-Related Anorexia-Cachexia Syndrome (CACS), is characterized by a ne...

E45 - Use of The Mini Nutritional Assessment to determine the Prevalence of Malnutrition And Cachexia In Patients Undergoing Surgery For Colorectal Carcinoma

Background: The cancer disease is the clinical condition most often associated with the concept of protein-calorie malnutrition that affects 8% to 84% of cancer patients and can worsen until determining cachexia also called “Wasting Disease”. Cancer-Related Anorexia-Cachexia Syndrome (CACS), is a complex metabolic syndrome characterized by a negative protein balance and energy caused both by a reduced caloric intake from both metabolic abnormalities associated with loss of muscle mass with or without loss of mass fat and considerable weight loss; it is estimated that about 20% of all cancer deaths occur for malnutrition. It is necessary to complement clinical examination of the patient also with review the nutritional status in order to evaluate the therapeutic process in these patients. Objective: The aim of this study was to assess the prevalence of malnutrition or the risk of malnutrition in patients undergoing to surgery for colorectal carcinoma. Methods: A total of 53 patients, 26 male and 27 female media age: 70,5 (42-86 yrs) undergoing to surgery for colorectal carcinoma in our Institute between November 2014 and April 2015, were evaluated to determine individual nutritional status, using the Mini Nutritional Assessment (MNA®) that includes 18 items grouped in four rubrics: anthropometric assessment, general assessment and lifestyle, short dietary assessment and subjective perception of health and nutrition. Results: The overall mean score for the MNA, was 26.2 ± 13.2 (range 6.0-27.0);15/53 patients (24.5%) presented a normal nutritional status (mean 24.8; range 24.0 to 27.5), 25/53 (47%) reported a risk of malnutrition while 13/53 (24.5%) reported a severe malnutrition that was found to be more common in men than in women. Besides, all malnourished patients had in the previous six months from the date of diagnosis, a significant weight loss (> 10 kg), muscle mass loss and severe reduction in the intake of food due loss of appetite and altered taste perception. Instead, patients at risk for malnutrition reported a weight loss of 3 to 5 kg and a moderate reduction in food intake. Conclusions: More than 50% of patients had moderate or severe malnutrition and the majority of them needed nutritional intervention before and during chemotherapy. Our preliminary data show the importance of nutritional assessment in cancer patients in order to set the appropriate treatment plan, improve its quality of life and increase overall survival in cancer patient.

Pharmacologic Therapy for Cancer Anorexia-Cachexia Syndrome

Cancer-related anorexia-cachexia syndrome (CACS) is a hypercatabolic state, characterized by reduced appetite and weight loss due to ongoing loss of skeletal muscle mass and adipose tissue. CACS occurs mainly in patients with advanced cancer; thus, weight loss in CACS is often associated with poor prognosis and decreased survival. A large number of studies have been conducted on various pharmacologic agents for palliation of cancer-related anorexia. The purpose of this article is to review the pre-existing pharmacologic agents used for CACS and to evaluate the evidence from current studies on each pharmacologic agent. First, appetite stimulants such as corticosteroids, progestins, cyproheptadine, and cannabinoid have been shown to be beneficial by improving appetite and helping with weight changes even if they had no effect on survival rate. Several other agents with anti-inflammatory effects (e.g., eicosapentaenoic acid, thalidomide, and melatonin), prokinetic agents (e.g., metoclopramide), anabolic agents (e.g., androgens and growth hormone), antipsychotics (e.g., mirtazapine and olanzapine), and antiemetics have also been studied in patients in CACS; however further investigations would be required to confirm the beneficial effects.

Abstract 1153: Effective treatment of cancer associated cachexia by AV-380, a GDF15 inhibitory antibody

Abstract Background: One of the most lethal and debilitating effects of cancer is the development of cancer-related anorexia-cachexia syndrome (CACS). It affects the majority of advanced cancer patients and is thought to be responsible for up to ∼30% of all cancer deaths. CACS is a complex metabolic syndrome associated with malnutrition and severe involuntary weight loss due to the loss of muscle and fat tissue, as well as the clinical manifestation of anemia, inflammation and suppression of immune functions. The precise molecular mechanisms responsible for cancer cachexia are poorly understood, thus limiting the development of effective therapeutics. Current evidence suggests that a pro-inflammatory state may be responsible for many of the symptoms associated with CACS. Growth Differentiation Factor 15 (GDF15) is a pro-inflammatory cytokine whose circulating levels are significantly increased in cachectic cancer patients and several animal models of cancer cachexia. Here we demonstrate that the inhibition of GDF15 function results in the compete reversion of the phenotypic and metabolic changes associated with CASC. Methods: Mice bearing HT-1080 human fibrosarcoma xenografts have increased plasma GDF15 levels and develop cachexia were used in this study. Tumor bearing animals were treated either with AV-380, a GDF15 neutralizing antibody or IgG1 control. The effect on body weight, muscle/fat mass and organ sizes were assessed. Metabolic changes induced by the treatment were measured by a comprehensive laboratory animal monitoring system (CLAMS). Results: Treatment with AV-380 restored body weight, muscle and fat mass as well as normal organ sizes. Analyses of the CLAMS data demonstrated that mice receiving AV-380 reversed the phenotypic and metabolic changes associated with the cachexia induced by this tumor model. Moreover, AV-380 treated mice showed an increase in locomotor activity and energy expenditure, achieving levels similar to non tumor bearing control animals. Conclusions: Inhibition of GDF15 function completely reverted body weight loss, restored normal body composition and triggered a catabolic to anabolic metabolic switch in this cancer cachexia model. The data highlights the therapeutic potential of the GDF15 inhibitory antibody AV-380 for the treatment for CACS. Citation Format: Lorena Lerner, Nianjun Tao, Brian Krieger, Richard Nicoletti, Bin Feng, Nesreen Ismail, William Winston, Yanyu Zhang, Jinwei Jiang, Solly Weiler, Jeno Gyuris. Effective treatment of cancer associated cachexia by AV-380, a GDF15 inhibitory antibody. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1153. doi:10.1158/1538-7445.AM2015-1153

Health professionals' attitudes toward the detection and management of cancer-related anorexia-cachexia syndrome, and a proposal for standardized assessment.

The identification and management of patients with cancer anorexia-cachexia syndrome (CACS) can be a challenge despite recent international consensus on the definition of the condition. To describe the current views and practice patterns of community oncologists and oncology nurses in regard to CACS and to propose a standardized, pragmatic assessment of CACS for oncological practice. Responses from 151 community oncologists and nurses obtained across 5 surveys were analyzed. Questions addressed CACS in general and in patients with non-small-cell lung cancer (NSCLC). Surveys 1-3 were directed at physicians, and surveys 4 and 5 were directed at nurses. Surveys 1, 2, 4, and 5 focused on the recognition and monitoring of CACS, and Survey 3 on symptom management. 67% of medical oncologists in Survey 3 selected weight loss as the most important criterion for diagnosing CACS and cited declining appetite and performance status (PS) as the most bothersome effects for patients and families. Weight maintenance/gain was the primary treatment objective for oncologists. Respondents to surveys 1 and 2 acknowledged the risk for CACS is high (60%) in NSCLC but considered the risk much lower (4%) in patients completing a first course of therapy with good PS. 91% of oncologists in Survey 3 reported that symptoms that had an impact on calorie intake were important/very important, and 73% were willing to consider a symptom assessment instrument that included appetite. Nurses in surveys 4 and 5 reported weight loss and appetite were most commonly used to identify cachexia. They considered responsibility for the initial assessment of cachexia was the oncologist's (32%), followed by the nurse practitioner (28%), and the nurse (16%). Most oncologists and nurses recognize the core criteria for the CACS, although there may be under-recognition of the condition's prevalence, particularly earlier in the course of treatment. There is considerable interest in adopting a brief assessment tool for screening, management, and referral of patients who are affected by or at-risk of CACS.

Demystifying Nutritional Support in Cancer (FR451)

•Describe the pathophysiology and stages of the cancer-related anorexia-cachexia syndrome.•Describe methods to assess cancer-related anorexia-cachexia at the bedside.•Describe the interventions according to stages of cancer-related anorexia-cachexia. Central to managing nutrition in the cancer patient is recognizing and managing the anorexia-cachexia syndrome. Research characterizes the anorexia-cachexia syndrome as a metabolic syndrome associated with advanced cancer producing loss of muscle with or without the loss of fat mass. Its development is a turning point in the disease trajectory of a cancer patient, with continued weight loss associated with a shorter survival time, and it is responsible for death in up to 20% of cancer patients. Anorexia-cachexia is a significant cause of morbidity that manifests as weight loss, asthenia (loss of energy and strength), anemia, and alterations in immune function. Research now recognizes anorexia-cachexia as a continuum consisting of three stages, defined as precachexia, cachexia, and refractory cachexia. Not all patients traverse the entire spectrum. Interventions potentially modifying the effect of anorexia-cachexia differ according to stages. Patients are often inappropriately recommended extreme types of nutritional support according to the stage of cancer and extent of the metabolic syndrome. Patients also experience messages that force them to adhere to therapies that are no longer appropriate for the stage of anorexia-cachexia. From presenters with diverse backgrounds in oncology, nursing, cachexia research, and community palliative care, and through didactics, case presentations, and audience participation, the session will accomplish four major goals for the attendees: (1) enhance knowledge of the basic pathophysiology of the anorexia-cachexia syndrome, (2) improve clinical assessment of anorexia-cachexia with a focus on clinical bedside assessment and technological advances, (3) characterize interventions according to stage of anorexia-cachexia, and (4) develop attendees’ skills at communicating with patients and families about cancer and nutrition. When this session is completed, palliative care specialists will walk away better equipped to participate in complex nutritional decision making for cancer patients.

Efficacy and safety of a two drug-combination regimen for cancer-related cachexia in the clinical practice.

e20556 Background: To test the safety and efficacy of a combination treatment (including nutraceuticals, i.e. quercetin, alpha lipoic acid and curcumin) with carnitine + celecoxib for the treatment of cancer-related anorexia/cachexia syndrome (CACS) in the clinical practice. Primary endpoints: safety, increase of lean body mass (LBM) and improvement of quality of life. Secondary endpoints: increase of physical performance (tested by grip strength and 6-min walk test, 6MWT) and decrease of inflammation (assessed by serum levels of IL-6 and Glasgow prognostic score, GPS). Methods: Outpatients with advanced cancer at different sites with CACS (i.e. loss of body weight &gt;5% of the pre-illness or ideal weight in the previous 3 months) were eligible to receive: L-carnitine 4 g/day + Celecoxib 300 mg/day. All patients received as basic treatment polyphenols 300 mg/day, lipoic acid 300 mg/day, carbocysteine 2.7 g/day, Vitamin E, A, C, all orally. Treatment duration was 4 months. Results: From June 2011 to April 2012, 75 patients with advanced cancer (all stage IV) at different sites were enrolled: 40 completed the treatment and were evaluable (mean age 65 ± 9.6, range 32-82 years). Results showed a significant increase of LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) from baseline as well as physical performance assessed by 6MWT. Quality of life (assessed by EORTC-QLQ-C30) as well as fatigue (assessed by MFSI-SF) also improved significantly. ECOG PS and GPS decreased significantly. The treatment was safe, no grade 3–4 toxicities occurred and no patient had to discontinue the treatment due to severe adverse events. Conclusions: The results of the present study confirm the efficacy and safety of the two-drug combination regimen previously shown in a randomized clinical trial (Madeddu et al, Clinical Nutrition 31:176-182,2012). Therefore, this simple, feasible, effective, safe, with favorable cost-benefit profile, two-drug approach could be suggested in the clinical practice as a treatment for CACS.

What medications are effective in the treatment of anorexia/cachexia associated with advanced cancer?

Evidence-Based Answer Megestrol acetate is associated with improved appetite and weight gain in cancer-related anorexia-cachexia syndrome (CACS), but has not been shown to improve survival (SOR: A, meta-analysis). Thalidomide treatment results in less weight loss, but again any impact on survival is unknown (SOR: B, RCT). Eicosapentaenoic acid is not effective (SOR: B, meta-analysis of small RCTs).

Clinical Studies on the Treatment of Cancer Cachexia with Megestrol Acetate plus Thalidomide

Background: The management of cancer-related anorexia/cachexia syndrome (CACS) is a great challenge in clinical practice. To date, practice guidelines for the prevention and treatment of CACS are lacking. The authors conducted a randomized study to confirm the effectiveness and safety of treatment of CACS utilizing megestrol acetate (MA) plus thalidomide. Methods: One hundred and two candidates with CACS were randomly assigned to two treatment groups (trial group and control group): the trial group received MA (160 mg po, bid) plus thalidomide (50 mg po, bid), while the control group received MA (160 mg po, bid) alone. Treatment duration was 8 weeks. Results: Analysis of the trial group demonstrated a significant increase from baseline in body weight (<0.01), quality of life (p = 0.02), appetite (p = 0.01), and grip strength (p = 0.01), and a significant decrease in fatigue, Glasgow Prognostic Score (p = 0.05), Eastern Cooperative Oncology Group performance status (p = 0.03), IL-6 (p < 0.01), and tumor necrosis factor-α (p = 0.02). In contrast, in the control group, endpoints with a significant improvement from baseline included body weight (p < 0.02) and appetite (p = 0.02). The mean changes in the endpoints from baseline in the trial group were significantly greater compared with the control group: in the primary endpoints, body weight (p = 0.05), fatigue (p < 0.01) and quality of life (p = 0.01), and in the secondary endpoints, grip strength (p = 0.05), Glasgow Prognostic Score (p = 0.02), Eastern Cooperative Oncology Group performance status (p = 0.02), IL-6 (p < 0.01) and tumor necrosis factor-α (p = 0.01). Toxicity was found to be relatively negligible in both groups. Conclusion: A combination regimen of MA and thalidomide is more effective than MA alone in the treatment of CACS.

1422O - Efficacy and Safety of a Two Drug-Combination Regimen for Cancer-Related Cachexia in the Clinical Practice

ABSTRACT Background and aims To test the safety and efficacy of a two-drug combination (including nutraceuticals, i.e. antioxidants) with carnitine + celecoxib for the treatment of cancer-related anorexia/cachexia syndrome (CACS) in the clinical practice. Primary endpoints: safety, increase of lean body mass (LBM) and improvement of quality of life. Secondary endpoints: increase of physical performance (tested by grip strength and 6-min walk test, 6MWT) and decrease of inflammation (assessed by serum levels of IL-6 and Glasgow prognostic score, GPS). Patients and methods Outpatients with advanced cancer at different sites with CACS (i.e. loss of body weight >5% of the pre-illness or ideal weight in the last3 months) were eligible to receive: L-carnitine 4 g/day + Celecoxib 300 mg/day. All patients received as basic treatment polyphenols 300 mg/day, lipoic acid 300 mg/day, carbocysteine 2.7 g/day, Vitamin E, A, C, all orally. Treatment duration was4 months. Results From June 2011 to April 2012, 50 patients with advanced cancer (all stage IV) at different sites were enrolled: 40 completed the treatment and were evaluable (mean age 63.8 ± 9.6, range 32-81 years). Results showed a significant increase of LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) from baseline as well as physical performance assessed by 6MWT. Quality of life (assessed by EORTC-QLQ-C30 and EQ-5D) also improved significantly. ECOG PS and GPS decreased significantly. The treatment was safe, no grade 3–4 toxicities occurred and no patient had to discontinue the treatment due to severe adverse events. Conclusions The results of the present study confirm the efficacy and safety of the two-drug combination regimen previously shown in a randomized clinical trial (Madeddu et al, Clinical Nutrition 31:176-182, 2012). Therefore, this simple, feasible, effective, safe, with favorable cost-benefit profile, two-drug approach could be suggested in the clinical practice as a treatment for CACS. Disclosure All authors have declared no conflicts of interest.

Abstract 2652: Randomized phase III clinical trial of a combined treatment with carnitine + celecoxib +/− megestrol acetate for patients with cancer-related anorexia/cachexia syndrome

Abstract Aims: A phase III, randomized non-inferiority study was carried out to compare a two-drug combination (including nutraceuticals, i.e. antioxidants) with carnitine + celecoxib +/− megestrol acetate for the treatment of cancer-related anorexia/cachexia syndrome (CACS): the primary endpoints were increase of lean body mass (LBM) and improvement of total daily physical activity. Secondary endpoint was: increase of physical performance tested by grip strength and six minute walk test. Methods: Sixty eligible patients were randomly assigned to: arm 1, L-carnitine 4 g/day + Celecoxib 300 mg/day or arm 2, L-carnitine 4 g/day + celecoxib 300 mg/day + megestrol acetate 320 mg/day, all orally. All patients received as basic treatment polyphenols 300 mg/day, lipoic acid 300 mg/day, carbocysteine 2.7 g/day, Vitamin E, A, C. Treatment duration was 4 months. Planned sample size was 60 patients. Results: The results did not show a significant difference between treatment arms in both primary and secondary endpoints. Analysis of changes from baseline showed that LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) increased significantly in both arms as well as physical performance assessed by 6MWT. Toxicity was quite negligible and comparable between arms. Conclusions: The results of the present study showed a non-inferiority of arm 1 (two drug-combination) vs arm 2 (two drug-combination + megestrol acetate). Therefore, this simple, feasible, effective, safe, low cost with favourable cost-benefit profile, two-drug approach could be suggested in the clinical practice to implement CACS treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2652. doi:1538-7445.AM2012-2652

Multitargeted Treatment of Cancer Cachexia

Cancer cachexia is defined as a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. The prominent clinical feature of cachexia is weight loss in adults. Anorexia, inflammation, insulin resistance, and increased muscle protein breakdown frequently are associated with cachexia. One single therapy may not be completely successful in the treatment of cachexia because of the complexity of the pathogenesis and symptoms of the cachexia syndrome. Among effective treatments, progestogens currently are considered the best available treatment option and are the only approved drugs in Europe for the treatment of cancer- and AIDS-related cachexia. However, they have limited efficacy in treating cancer cachexia. However, thalidomide, selective COX-2 inhibitors, ghrelin mimetics, and selective androgen receptor modulators showed promising results but should be defined further and confirmed in clinical trials. Therefore, to date, despite several years of coordinated efforts in basic and clinical research, the practice guidelines for the prevention and treatment of cancer-related anorexia cachexia syndrome (CACS) are lacking. The management of CACS is a complex challenge that should address the different causes underlying this clinical event. Recent studies showed that integrated, multitargeted approaches are more effective than single-agent approaches for the treatment of CACS. Further clinical trials to improve and refine current strategies to counteract cancer cachexia using multimodal interventions, including nutritional supplementation, anabolic agents, and antiinflammatory drugs along with an appropriate physical exercise program, are warranted.

Randomized phase III clinical trial of a combined treatment with carnitine + celecoxib ± megestrol acetate for patients with cancer-related anorexia/cachexia syndrome

A phase III, randomized non-inferiority study was carried out to compare a two-drug combination (including nutraceuticals, i.e. antioxidants) with carnitine + celecoxib ± megestrol acetate for the treatment of cancer-related anorexia/cachexia syndrome (CACS): the primary endpoints were increase of lean body mass (LBM) and improvement of total daily physical activity. Secondary endpoint was: increase of physical performance tested by grip strength and 6-min walk test. Sixty eligible patients were randomly assigned to: arm 1, L-carnitine 4 g/day + Celecoxib 300 mg/day or arm 2, L-carnitine 4 g/day + celecoxib 300 mg/day + megestrol acetate 320 mg/day, all orally. All patients received as basic treatment polyphenols 300 mg/day, lipoic acid 300 mg/day, carbocysteine 2.7 g/day, Vitamin E, A, C. Treatment duration was 4 months. Planned sample size was 60 patients. The results did not show a significant difference between tre atment arms in both primary and secondary endpoints. Analysis of changes from baseline showed that LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) increased significantly in both arms as well as physical performance assessed by 6MWT. Toxicity was quite negligible and comparable between arms. The results of the present study showed a non-inferiority of arm 1 (two-drug combination) vs arm 2 (two-drug combination + megestrol acetate). Therefore, this simple, feasible, effective, safe, low cost with favorable cost-benefit profile, two-drug approach could be suggested in the clinical practice to implement CACS treatment.

Innovative Treatment Approach for Cancer-Related Cachexia

Cachexia is a complex metabolic syndrome associated with many chronic or end-stage diseases, especially cancer, and is characterized by loss of muscle with or without loss of fat mass. The management of cancer-related anorexia/cachexia syndrome (CACS) is a complex challenge that should address the different causes underlying this clinical event with an integrated or multimodal treatment approach targeting the different factors involved in its pathophysiology. Among the treatments proposed in the literature for CACS, some proved to be ineffective, namely, cyproheptadine, hydrazine, metoclopramide, and pentoxifylline. Among effective treatments, progestagens are currently considered the best available treatment option for cancer-related cachexia, and they are the only drugs approved in Europe. Drugs with a strong rationale that have failed or have not shown univocal results in clinical trials so far include eicosapentaenoic acid, cannabinoids, bortezomib, and anti-TNF-α MoAb. Several emerging drugs have shown promising results but are still under clinical investigation (thalidomide, selective cyclooxygenase-2 (COX-2) inhibitors, ghrelin mimetics, insulin, oxandrolone, and olanzapine). However, to date, despite several years of co-ordinated efforts in basic and clinical research, practice guidelines for the prevention and treatment of cancer-related muscle wasting are lacking, mainly because of the multifactorial pathogenesis of the syndrome. From all the data presented, one can speculate that one single therapy may not be completely successful in the treatment of cachexia. A more effective approach might be a combination therapy targeting the different mechanisms contributing to CACS.

Randomized phase III clinical trial of two different arms of a combined treatment with carnitine plus celecoxib with or without megestrol acetate for patients with cancer-related anorexia/cachexia syndrome (CACS).

e19733 Background: Cancer-related anorexia/cachexia syndrome (CACS) is a multifactorial syndrome characterized by loss of lean body mass (LBM), metabolic alterations, chronic inflammation and fatigue. Methods: In October 2009 we started a phase III randomised study to establish which was the most effective and safest treatment to improve the “key” variables of CACS: increase of LBM, decrease of resting energy expenditure (REE), improvement of fatigue (MFSI-SF) and physical activity (ArmBand). As secondary endpoints we evaluated: grip strength, six minute walk test (6MW), appetite, serum levels of IL-6 and TNF-a, EORTC-QLQ-C30, Glasgow Prognostic Score (GPS), ECOG PS. All patients received as basic oral treatment poliphenols + alpha lipoic acid + carbocysteine + Vitamins A,C,E and were then randomly assigned to: L-carnitine 4 g/d + Celecoxib 300 mg/d (Arm 1) or the same treatment + megestrol acetate (MA) 320 mg/d (Arm 2). Treatment duration: 4 months. The planned sample size was 70 patients for each arm. An interim analysis (intent-to treat) was planned. Results: Sixty cachectic patients (mean age 65.2 ± 8.7 years) with tumors at different sites were enrolled and 57 were evaluable (3 died early due to disease progression). Analysis of changes from baseline showed that LBM assessed by DEXA as well as by L3-CT improved in both arms. Fatigue improved significantly in both arms. REE and physical activity did not show significant changes. As for secondary endpoints, the 6MW test, appetite, GPS and ECOG PS improved significantly. The comparison between the 2 arms by ANOVA test did not show a significant difference. Toxicity was substantially negligible and comparable between arms (1 grade 3 diarrhea in arm 1 and 2, which led to the withdrawal of carnitine for 2 weeks). Conclusions: Both arms showed to be effective as for primary efficacy endpoints (improvement of LBM and fatigue) and some important secondary endpoints. The results of the present trial confirm the efficacy of a combined approach for the treatment of CACS: arm 1, without MA, could be the treatment of choice as it was effective and easier to administer. The trial is ongoing.

Cancer-Related Anorexia-Cachexia Syndrome

Cancer-related anorexia-cachexia syndrome (CACS) is an under-recognized component of accelerated mortality and morbidity in patients with advanced cancer. The lack of desire to eat also can create tension and conflict between patients and their families. Advanced practice nurses play a vital role in ensuring early assessment and interventions for patients with CACS.

PP19 Randomised phase III clinical trial of 5 different arms of treatment for patients with cancer-related anorexia/cachexia syndrome (CACS)

PP19 Randomised phase III clinical trial of 5 different arms of treatment for patients with cancer-related anorexia/cachexia syndrome (CACS)