anamorelin and Body-Weight

Anamorelin was approved for production and marketing in Japan on 22 January 2021 for cancer cachexia in non-small-cell lung cancer, gastric cancer, pancreatic cancer, and colorectal cancer. The authors describe the updates of anamorelin for cancer cachexia in Japan.. Recent evidence showed that anamorelin improved lean body mass, body weight, and appetite in patients with cancer cachexia in clinical practice. Anamorelin does not increase body weight in the severe-weight-loss group in cachectic patients with pancreatic cancer. Several case reports showed that anamorelin can cause cardiac adverse drug reactions. Among the cardiac adverse reactions, fatal arrhythmias should be monitored carefully even if it is the first dose. Anamorelin combined with nutrition, physical activity, and exercise may be more useful than anamorelin alone for treating cancer cachexia. An interim analysis from post-marketing all-case surveillance was performed; however, details have not yet been published. When anamorelin cannot be used for cancer cachexia, Kampo medicines can be considered as an option.. Anamorelin has changed the clinical practice of cancer cachexia in Japan. The authors hope that anamorelin is available for other disease-related cachexia along with appropriate multidisciplinary interventions.

Topics: Body Weight; Cachexia; Carcinoma, Non-Small-Cell Lung; East Asian People; Humans; Lung Neoplasms; Neoplasms; Pancreatic Neoplasms

Cancer cachexia is a multilayered syndrome consisting of the interaction between tumor cells and the host, at times modulated by the pharmacologic treatments used for tumor control. Key cellular and soluble mediators, activated because of this interaction, induce metabolic and nutritional alterations. This results in mass and functional changes systemically, and can lead to increased morbidity and reduced length and quality of life. For most solid malignancies, a cure remains an unrealistic goal, and targeting the key mediators is ineffective because of their heterogeneity/redundancy. The most beneficial approach is to target underlying systemic mechanisms, an approach where the novel non-peptide ghrelin analogue anamorelin has the advantage of stimulating appetite and possibly food intake, as well as promoting anabolism and significant muscle mass gain. In the ROMANA studies, compared with placebo, anamorelin significantly increased lean body mass in non-small cell lung cancer (NSCLC) patients. Body composition analysis suggested that anamorelin is an active anabolic agent in patients with NSCLC, without the side effects of other anabolic drugs. Anamorelin also induced a significant and meaningful improvement of anorexia/cachexia symptoms. The ROMANA trials have provided unprecedented knowledge, highlighting the therapeutic effects of anamorelin as an initial, but significant, step toward directly managing cancer cachexia.

Topics: Body Weight; Cachexia; Carcinoma, Non-Small-Cell Lung; Ghrelin; Hand Strength; Humans; Hydrazines; Oligopeptides

Cancer cachexia affects many patients with advanced cancer. This multifactorial syndrome, which involves loss of muscle mass and body weight, profoundly affects patients' physical functioning and quality of life. Pharmacologic interventions that target weight loss and also improve patient-reported measures are required. Anamorelin hydrochloride is an oral ghrelin receptor agonist for the treatment of cancer anorexia-cachexia that stimulates release of growth hormone and insulin-like growth factor 1, and improves food intake and body weight. Phase II and III trials have demonstrated that anamorelin increases body muscle and fat composition, and improves patient-reported appetite and quality of life. Anamorelin shows promise as an anabolic agent with benefits maintained over time, without the virilizing side effects of other anabolic medications.

Topics: Anorexia; Body Composition; Body Weight; Cachexia; Clinical Trials as Topic; Disease Management; Humans; Hydrazines; Neoplasms; Oligopeptides; Treatment Outcome

Cancer anorexia-cachexia syndrome (CACS) is characterized by involuntary weight loss. CACS is commonly observed in advanced non-small-cell lung cancer (NSCLC), and it leads to a poor quality of life (QOL). No effective standard treatment exists for this condition. However, anamorelin has reportedly caused improvement in patients with several cancers.. We conducted a quantitative meta-analysis to explore the efficacy of anamorelin for treating CACS in patients with NSCLC. We systematically searched CENTRAL, MEDLINE, EMBASE, CINAHL, and OvidSP. We pooled the data and calculated and compared total body weight (TBW), lean body mass (LBM), overall survival (OS), hand grip strength (HGS), QOL, and adverse events (AEs) between patients treated with anamorelin (anamorelin group) and those not (placebo group).. Six randomized controlled trials included 1641 patients with NSCLC. Both TBW and LBM were significantly increased in the anamorelin group compared to the placebo group (mean differences [MD] 1.78, 95%CI: 1.28-2.28, p<0.00001; MD 1.10, 95%CI: 0.35-1.85, p=0.004, respectively). The groups showed no difference in OS or HGS (hazard ratio 0.99, 95%CI: 0.85-1.14, p=0.84; MD 0.52, 95% CI: -0.09-1.13, p=0.09, respectively). Anamorelin significantly improved the QOL (standardized MD 0.19, 95%CI: 0.08-0.30, p=0.0006). The frequency of any AEs and grade 3 or 4 AEs were not significantly different between groups (risk ratio[RR] 1.03, 95%CI: 0.95-1.10, p=0.49; RR 0.86, 95%CI: 0.48-1.54, p=0.62).. This analysis demonstrated that anamorelin represents a promising treatment option for CACS in patients with advanced NSCLC.

Topics: Age Factors; Body Weight; Cachexia; Carcinoma, Non-Small-Cell Lung; Clinical Trials as Topic; Humans; Hydrazines; Lung Neoplasms; Odds Ratio; Oligopeptides; Quality of Life; Randomized Controlled Trials as Topic; Sex Factors; Treatment Outcome

Cachexia, a disorder associated with anorexia, inflammation, and muscle wasting, is frequent in cancer patients. We performed post-hoc analyses of the ONO-7643-04 study to investigate the efficacy and safety of anamorelin in subgroups of Japanese patients with non-small cell lung cancer (NSCLC).. The patients were divided into subgroups by baseline characteristics, including sex, age, body mass index, prior weight loss, performance status (PS), concomitant anticancer therapy, and number of previous chemotherapy regimens. The changes from baseline through to 12 weeks for lean body mass (LBM), body weight, and appetite were calculated. Appetite was evaluated using the quality of life questionnaire for cancer patients treated with anticancer drugs (QOL-ACD) item 8 score. Responder rates were defined as the maintenance/improvement of LBM (≥0 kg), body weight (≥0 kg), or QOL-ACD item 8 score (≥0) from baseline to all evaluation time points. Safety was evaluated in patients subgrouped by age and PS.. Anamorelin resulted in greater improvements versus placebo in LBM, body weight, and appetite in most subgroups. Anamorelin was also associated with greater LBM, body weight, and appetite responder rates than placebo in nearly all subgroups. Among anamorelin-treated patients, adverse drug reactions (ADRs) tended to be more frequent with increasing age (<65 years, 19.2%; ≥65 to <75 years, 45.9%; ≥75 years, 60.0%) and PS score (PS 0-1, 38.4%; PS 2, 60.0%). The frequency of serious ADRs was 2.7% and 0% in the PS 0-1 and PS 2 subgroups, respectively.. This study of NSCLC patients with cancer cachexia revealed consistent improvements in LBM, body weight, and appetite across most subgroups of anamorelin-treated patients. This study also demonstrated the tolerability of anamorelin regardless of age and PS, with a low incidence of serious ADRs in each subgroup.

Topics: Aged; Body Weight; Cachexia; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Neoplasms; Quality of Life

RC-1291 is a novel, oral ghrelin mimetic and growth hormone (GH) secretagogue being developed to increase appetite and lean muscle mass in patients with cancer-associated anorexia/cachexia. This randomized, double-blind, placebo-controlled, multiple-dose, dose-escalation phase I study in healthy volunteers evaluated RC-1291 once daily (qd) and twice daily (bid) for effect on body weight and safety.. The study was conducted with three sequential groups of volunteers. Panel A subjects (n = 8) received placebo or RC-1291, 25 mg qd, for 5 days. Panel B subjects received RC-1291, 25 mg bid or 50 mg qd, for 6 days then crossed over to the other dosage for 5 days (n = 12); three subjects received placebo for all 11 doses to maintain double-blinding. Panel C subjects (n = 9) received placebo or RC-1291, 75 mg qd, for 6 days.. Subjects who received RC-1291, 50 or 75 mg, had significant dose-related weight gain after 6 days versus placebo, with the greatest increases seen with daily dosing. The mean increase in weight from baseline after 50 mg qd was 1.25 +/- 0.725 kg (p = .0022 versus placebo), and after 75 mg qd it was 1.16 +/- 0.651 kg (p = .0022 versus placebo). One subject in the 50 mg qd group had moderate transient elevation in aspartate aminotransferase and alanine aminotransferase levels. No other laboratory or clinical adverse events of consequence were reported.. Results indicate that RC-1291 produces dose-related increases in body weight with no dose-limiting adverse effects, and may be an effective treatment for anorexia/cachexia.

Topics: Administration, Oral; Adult; Alanine Transaminase; Analysis of Variance; Aspartate Aminotransferases; Biomarkers; Blood Pressure; Body Weight; Dose-Response Relationship, Drug; Double-Blind Method; Female; Ghrelin; Humans; Male; Receptors, Ghrelin; Reference Values; Time Factors; Treatment Outcome

Objective Anamorelin, a novel selective ghrelin receptor agonist, was approved in Japan for the treatment of cachexia in pancreatic cancer (PC), albeit with limited evidence. This study evaluated the efficacy and safety of anamorelin in PC and examined the impact of the extent of weight loss on the efficacy of anamorelin. Methods We retrospectively investigated consecutive PC patients with cachexia who received anamorelin at our institution between June 2021 and January 2022. Patients were divided into two groups: moderate-weight-loss group (5-10%) and severe-weight-loss group (>10%). The primary outcome was changes in body weight. The secondary outcomes were changes in appetite and laboratory measures as well as treatment-related severe adverse events. Results A total of 24 patients were included (moderate/severe weight loss: 8/16). The moderate-weight-loss group showed significantly more weight gain than the severe-weight-loss group. Improvements in appetite were consistently observed in each weight-loss group. Changes in laboratory markers were not significantly different between groups. Hyperglycemia (four patients) was the most common cause of severe adverse events, followed by abdominal distension, nausea, elevated liver function tests, and bulimia. Conclusion The efficacy of anamorelin was associated with the extent of weight loss. Although anamorelin improved appetite in each weight-loss group, it increased body weight only in the moderate-weight-loss group. Anamorelin was well-tolerated among advanced PC patients, although caution must be practiced when it is used in patients with concomitant diabetes mellitus.

Topics: Anorexia; Body Weight; Cachexia; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Neoplasms; Pancreatic Neoplasms; Retrospective Studies

Cancer cachexia is a syndrome characterized by anorexia and decreased body weight. This study evaluated the efficacy and safety of anamorelin, an orally active, selective ghrelin receptor agonist, in patients with cancer cachexia and a low body mass index (BMI).. Anamorelin improved body weight and anorexia-related symptoms in patients with cancer cachexia and a low BMI with durable efficacy and favorable safety and tolerability.. Anamorelin is a drug that stimulates appetite and promotes weight gain. This clinical trial was aimed at determining its efficacy and safety in Japanese cancer patients with a low body mass index and cachexia, a syndrome associated with anorexia and weight loss. Anamorelin was found to improve body weight and anorexia-related symptoms in these patients, and these effects were durable for up to 24 weeks. Moreover, anamorelin was generally well tolerated. These findings suggest that anamorelin is a valuable treatment option for patients with cancer cachexia and a low body mass index.

Topics: Anorexia; Body Mass Index; Body Weight; Cachexia; Carcinoma, Non-Small-Cell Lung; Ghrelin; Humans; Hydrazines; Lung Neoplasms; Oligopeptides

Anamorelin (ONO-7643) is an orally active ghrelin receptor agonist in development for non-small cell lung cancer (NSCLC)-related anorexia/cachexia. It displays both orexigenic and anabolic properties via ghrelin mimetic activity and transient increases in growth hormone (GH). However, increasing GH and insulin-like growth factor-1 in cancer patients raises concerns of potentially stimulating tumor growth. Therefore, we investigated the effect of ghrelin and anamorelin on tumor growth in a murine NSCLC xenograft model.. Female nude mice (15-21/group) with established A549 tumors were administered ghrelin (2 mg/kg i.p.), anamorelin (3, 10, or 30 mg/kg p.o.), or vehicle controls daily for 28 days. Tumor growth, food consumption, and body weight were monitored. Murine growth hormone (mGH) and murine insulin-like growth factor-1 (mIGF-1) were measured in plasma.. Tumor growth progressed throughout the study, with no significant differences between treatment groups. Daily food consumption was also relatively unchanged, while the percentage of mean body weight gain at the end of treatment was significantly increased in animals administered 10 and 30 mg/kg compared with controls (p < 0.01). Peak mGH levels were significantly higher in ghrelin- and anamorelin-treated animals than in controls, while peak mIGF-1 levels were slightly elevated but not statistically significant. All regimens were well tolerated.. These findings demonstrate that neither anamorelin nor ghrelin promoted tumor growth in this model, despite increased levels of mGH and a trend of increased mIGF-1. Together with anamorelin's ability to increase body weight, these results support the clinical development of ghrelin receptor agonist treatments for managing NSCLC-related anorexia/cachexia.

Topics: Animals; Anorexia; Body Weight; Cachexia; Carcinoma, Non-Small-Cell Lung; Disease Models, Animal; Eating; Female; Ghrelin; Growth Hormone; Humans; Insulin-Like Growth Factor I; Lung Neoplasms; Mice; Mice, Nude; Receptors, Ghrelin; Weight Gain; Xenograft Model Antitumor Assays