Treatment Of Cancer Anorexia-cachexia Syndrome Research Articles

A Review of Olanzapine in the Treatment of Cancer Anorexia-Cachexia Syndrome.

Cancer anorexia-cachexia syndrome (CAS) is a multifactorial condition that is highly prevalent in advanced cancer patients and associated with significant reduction in functional performance, reduction in quality of life, and increased mortality. Currently, no medications are approved for this indication. Recently, the American Society of Clinical Oncology (ASCO) released a rapid recommendation suggesting that low-dose olanzapine once daily may be used to treat cancer cachexia. Many questions still exist on how to use olanzapine for this indication in clinical practice. The objective of this review is to identify existing knowledge on the use of olanzapine for CAS. A comprehensive search was conducted to identify the primary literature that involved olanzapine for anorexia and cachexia in cancer patients between 2000 and 2023. Seven articles were identified and are discussed here, including two randomized double-blinded placebo-controlled studies, one randomized comparative study, two prospective open-label studies, one retrospective chart review, and one case report. Low dose olanzapine (2.5-5 mg once daily) may be useful in the treatment of CAS for increasing appetite, reducing nausea and vomiting, and promoting weight gain. Further large-scale multi-center randomized placebo-controlled studies will be needed to investigate the impact of olanzapine on weight change in CAS patients.

1679P A double-blind, placebo-controlled, randomized phase IIa trial, evaluating the effect of curcumin for the treatment of cancer anorexia-cachexia syndrome in patients with stage III-IV head and neck cancer (CurChexia)

Cancer anorexia-cachexia syndrome (CAS) is a significant comorbidity in all cancer patients that increase the mortality rate. Almost all head and neck cancer (HNC) patients suffered from this syndrome. CAS causes increased energy expenditure by increased systemic inflammation and decreased energy consumption due to anorexia. This leads to skeleton muscle breakdown and affects the quality of life. Nutritional interventions and cancer treatment are the mainstays to treat this situation. However, a vicious cycle causes CAS to persist, especially in HNC, where tumor location and its treatment interfere with nutritional intervention.

The Effect ofCurcumin for Treatment of Cancer Anorexia-Cachexia Syndrome in Patients With Stage III-IV of Head and Neck Cancer

The Effect ofCurcumin for Treatment of Cancer Anorexia-Cachexia Syndrome in Patients With Stage III-IV of Head and Neck Cancer

A double-blind, placebo-controlled randomized phase II study: Evaluating the effect of curcumin for treatment of cancer anorexia-cachexia syndrome in solid cancer patients.

e23151 Background: Cancer anorexia–cachexia syndrome (CACS) is common among patients with advanced solid cancer and associated with poor prognosis. CACS is a hypercatabolic state, which comprises adipose tissue and skeletal muscle loss, which is characterized by negative protein and energy balance, loss of lean body mass and adipose tissue. Also, CACS increase systemic inflammation. The treatment of CACS is still unclear. Curcumin has been shown anti-cancer and anti-inflammatory effects, including attenuation of CACS in animal models. Therefore, clinical study of curcumin for CACS is required. Methods: This is randomized, double-blind, placebo-controlled phase ll study, 52 patients with CACS in solid malignancy were enrolled and randomized in 1:1 to receive oral curcumin (at a dose of 400 mg twice daily) or placebo for 8 weeks. The primary end point was body tissue composition and the secondary end points were body weight and body mass index, Hand grip muscle strengthening, safety and toxicity. Results: All parameters of body compositions were not statistically significant different between two groups: curcumin group and placebo group, which were consist body fat mass -0.9, SEM = 0.94 versus –1.65, SEM = 1 ( p-value = 0.58), skeletal muscle mass -0.17, SEM = 0.49 versus +0.4, SEM = 0.52 ( p-value = 0.42) and percent body fat –1.0, SEM = 0.65 versus -0.1, SEM = 0.68 ( p-value = 0.3) including with basal metabolic rate -5.3, SEM = 18 versus +18.3, SEM = 19 ( p-value = 0.37). The average of weight loss was also not statistically significant different between two groups, -1.04, SEM = 0.63 in curcumin group versus –1.15, SEM = 0.61 in placebo group, ( p-value = 0.9). Notably, patient with curcumin had less reduction of hand-grip muscle strength on both hands [right hand: -2.09 in curcumin versus -3.68 in placebo; p = 0.46], [left hand: -1.24 versus -5.04; p-value = 0.12], and basal metabolic rate than placebo group. Most adverse events were grade 1 on both groups similarly. Conclusions: Curcumin was not shown to be superior to placebo with regard to increasing the body composition in cancer patients with CACS. However, curcumin might show some clinical benefits, including slow progression of hand-grip muscle strength loss and basal metabolic rate. Further investigations should be explored.

Anamorelin HCl (ONO-7643), a novel ghrelin receptor agonist, for the treatment of cancer anorexia-cachexia syndrome: preclinical profile.

BackgroundAnamorelin HCl (ANAM) is a novel, orally active, ghrelin receptor agonist in clinical development for the treatment of cancer cachexia. We report in vitro and in vivo studies evaluating the preclinical pharmacologic profile of ANAM.MethodsFluorescent imaging plate reader and binding assays in HEK293 and baby hamster kidney cells determined the agonist and antagonist activity of ANAM, and its affinity for the ghrelin receptor. Rat pituitary cells were incubated with ANAM to evaluate its effect on growth hormone (GH) release. In vivo, rats were treated with ANAM 3, 10, or 30 mg/kg, or control orally, once daily for 6 days to evaluate the effect on food intake (FI) and body weight (BW), and once to assess GH response. In pigs, single (3.5 mg/kg) or continuous (1 mg/kg/day) ANAM doses were administered to assess GH and insulin-like growth factor (IGF-1) response.ResultsANAM showed significant agonist and binding activity on the ghrelin receptor, and stimulated GH release in vitro. In rats, ANAM significantly and dose-dependently increased FI and BW at all dose levels compared with control, and significantly increased GH levels at 10 or 30 mg/kg doses. Increases in GH and IGF-1 levels were observed following ANAM administration in pigs.ConclusionANAM is a potent and highly specific ghrelin receptor agonist with significant appetite-enhancing activity, leading to increases in FI and BW, and a stimulatory effect on GH secretion. These results support the continued investigation of ANAM as a potential treatment of cancer anorexia-cachexia syndrome.

Anamorelin Hydrochloride in the Treatment of Cancer Anorexia-Cachexia Syndrome

Anamorelin hydrochloride is an orally active ghrelin receptor agonist in development by Helsinn, for the treatment of non-small-cell lung cancer (NSCLC) cachexia. In preclinical and clinical studies, the potent affinity of anamorelin for the ghrelin receptor is associated with significant appetite-enhancing activity and resultant improvements in body weight, lean body mass, and handgrip strength compared with placebo. The accompanying stimulatory effects on growth hormone and IGF-1 are not associated with tumor growth, and overall survival in patients with cancer is not compromised. Anamorelin is well tolerated with no dose-limiting toxicities identified to date. The findings of ongoing Phase III studies are needed to confirm the significant potential of anamorelin to treat NSCLC cachexia.