Abstract
Background/Aim: Cachexia is a multifactorial syndrome that adversely affects the prognosis of patients with gastrointestinal cancer. Although anamorelin has been shown to improve appetite and body weight, the optimal timing of its initiation remains unclear. This study evaluated the effects of the timing of anamorelin initiation on nutritional recovery and clinical outcomes in patients with gastrointestinal cancer cachexia.
Patients and Methods: We retrospectively reviewed 42 patients with gastric (n=17) or colorectal cancer (n=25) complicated by cachexia who received 100 mg of anamorelin once daily between August 2021 and December 2024. Changes in body weight, food intake, and nutritional status were assessed before and after anamorelin administration, and overall survival was analyzed according to the type of cancer.
Results: Initially, patients had experienced a mean body weight loss of 15.9±1.7% relative to the pre-diagnosis baseline. After four weeks, mean body weight increased by 2.9% (p<0.001), food intake improved significantly from 30.5%±0.3% to 57.1%±0.5% (p<0.001), and the Patient-Generated Subjective Global Assessment short form (PG-SGA SF) score decreased from 12.3±0.4 to 10.3±0.9 (p=0.003). The median overall survival was 17.9 months for gastric cancer and 36.8 months for colorectal cancer, with no significant difference between the two groups (p=0.089).
Conclusion: Anamorelin improved body weight, food intake, and nutritional status in patients with advanced gastrointestinal cancer cachexia. However, the modest degree of recovery suggests that earlier administration, before substantial weight and muscle loss, may maximize therapeutic benefits, support treatment continuity, and potentially improve survival outcomes. Therefore, early intervention should be considered in the clinical management of cancer cachexia.
Introduction
Cancer cachexia is a multifactorial syndrome characterized by the progressive loss of skeletal muscle mass, with or without depletion of fat mass, which cannot be fully reversed by conventional nutritional support (1). This syndrome significantly impairs physical function, quality of life, and survival in patients with advanced malignancies. Once substantial weight and muscle loss occur, the condition is often refractory to nutritional and pharmacological interventions (2).
Current treatment strategies for cancer cachexia remain limited, focusing primarily on nutritional supplementation and symptomatic management rather than on addressing the underlying metabolic and inflammatory disturbances. Anamorelin (ONO-7643) is an orally active, selective ghrelin receptor agonist that mimics the active N-terminal core of ghrelin (3, 4). Previous studies have demonstrated that anamorelin, which is relatively practically manageable agent, can safely improve body weight, lean body mass, and food intake in patients with various cancers (5-10).
However, in routine clinical practice, anamorelin is often initiated only after cachexia has advanced, when severe weight and muscle loss have already occurred. At this stage, anabolic and appetite-stimulating therapies may have limited effectiveness due to systemic inflammation, dominance of catabolic processes, and irreversible muscle wasting. The optimal timing for initiating anamorelin therapy remains unclear, and whether earlier administration yields greater clinical benefits has not been adequately investigated.
This study aimed to examine the impact of the timing of anamorelin initiation on nutritional recovery and clinical outcomes in patients with gastrointestinal cancer cachexia. We specifically sought to determine whether early intervention, prior to excessive weight and muscle loss, could maximize therapeutic benefits, maintain treatment continuity, and potentially improve survival outcomes.
Patients and Methods
Patients and intervention. This retrospective study included patients with gastric or colorectal cancer complicated by cachexia who received 100 mg of anamorelin once daily in the fasting state, in accordance with the dosing regimen established in previous phase III randomized trials (7), between August 2021 and December 2024 at the Department of Surgery and Gastroenterology, National Hospital Organization (NHO) Beppu Medical Center.
Cancer cachexia was defined as weight loss exceeding 5% within 6 months accompanied by anorexia, along with at least two of the following: 1) fatigue or malaise; 2) muscle weakness; and 3) at least one laboratory abnormality: C-reactive protein (CRP) >0.5 mg/dl, hemoglobin (Hb) <12 g/dl, or albumin (Alb) <3.2 g/dl (11).
Informed consent was obtained from each patient before starting the medication. All procedures performed in this study involving human participants were in accordance with the ethical standards of the NHO Beppu Medical Center Institutional Review Board and the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Data collection and assessment parameters. Patient data, including baseline characteristics, cancer type, clinical laboratory findings, weight change, and oncological outcomes, were extracted from medical records. Changes in body weight and food intake were evaluated before and after anamorelin administration. The relationship between weight change before treatment and subsequent changes in food intake was also examined. Nutritional status was assessed using the Patient-Generated Subjective Global Assessment short form (PG-SGA SF) (12) before and after treatment. Overall survival was analyzed separately for gastric and colorectal cancers.
Statistical analysis. All statistical analyses were performed using IBM SPSS Statistics version 28 (Chicago, IL, USA). Continuous variables are presented as the mean±standard error of the mean (SEM). Paired continuous variables were compared using a paired t-test or Wilcoxon signed-rank test, as appropriate. Changes in body weight and food intake were analyzed using analysis of variance (ANOVA). Cumulative survival rates were calculated using the Kaplan-Meier method. All tests were two-sided, and statistical significance was set at p<0.05.
Results
Demographic and clinical characteristics of patients. The clinical characteristics of the patients are summarized in Table I. A total of 42 patients with gastric cancer (n=17, 40.5%) or colorectal cancer (n=25, 59.5%) complicated by cancer cachexia received anamorelin during the study period. The mean age was 74.8±1.3 years, and 25 patients (59.5%) were male. An Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 or 3 was observed in 22 patients (52.4%). The mean body weight and body mass index (BMI) at baseline were 49.6±1.8 kg and 19.5±0.5 kg/m2, respectively. At the time of treatment initiation, the mean serum Alb and CRP levels were 3.0±0.1 g/dl and 3.8±0.8 mg/dl, respectively. A total of 29 (69.0%) patients underwent concomitant active cancer therapy.
Patient demographics and characteristics.
Weight change and food intake. At treatment initiation, patients experienced a mean body weight loss of 15.9±1.7% compared with their pre-diagnosis weight. The degree of weight loss for each cancer type is shown in Figure 1. After 4 weeks of anamorelin administration, the mean body weight increased by 2.9% from baseline.
Baseline weight loss (%) in patients with gastric and colorectal cancer.
Figure 2 shows that food intake improved significantly from baseline (mean 30.5%±0.3%) to 1 week (49.8%±0.4%) and 4 weeks (57.1%±0.5%) after anamorelin initiation (p<0.001). At 4 weeks, patients with baseline weight loss <15% demonstrated a significantly greater increase in food intake (mean+31.0%) compared with those with ≥15% weight loss (mean+23.1%, p<0.001) (Figure 3).
Change in food intake (%) from baseline to 4 weeks after anamorelin initiation.
Change in food intake (%) from baseline, 1 week, and 4 weeks after anamorelin initiation.
Malnutrition assessment. The mean PG-SGA SF score significantly decreased from 12.3±0.4 at baseline to 10.3±0.9 after four weeks of treatment (p=0.003), indicating improvement in nutritional status (Figure 4).
Change in Patient-Generated Subjective Global Assessment short form (PG-SGA SF) score from baseline to 4 weeks after anamorelin initiation.
Survival outcomes. The median follow-up duration was 31.4 months. Kaplan-Meier survival analysis demonstrated that the median overall survival was 17.9 months for patients with gastric cancer (n=17) and 36.8 months for those with colorectal cancer (n=25) (Figure 5). Although the difference was not statistically significant (p=0.089), both groups showed similar survival trends during the observation period.
Kaplan-Meier curves for overall survival in patients with gastric cancer and colorectal cancer.
Discussion
Cancer cachexia is a multifactorial syndrome characterized by involuntary weight loss, driven primarily by the wasting of skeletal muscle and adipose tissue, and is strongly associated with a poor prognosis in patients with gastrointestinal cancers. Once advanced, the disease is often refractory to nutritional or pharmacological interventions, underscoring the importance of timely therapeutic strategies. In this study, anamorelin significantly improved body weight, food intake, and nutritional status, even in patients with advanced cachexia who had already experienced a mean weight loss of nearly 16% before treatment initiation. These findings are consistent with those of previous phase III trials demonstrating the efficacy of anamorelin in improving lean body mass and appetite in patients with cancer cachexia (7).
However, despite the observed improvements, the degree of weight gain and nutritional recovery in our cohort was modest compared with that reported in earlier phase clinical trials. One plausible explanation is the late initiation of treatment in most patients, when cancer cachexia was already in an advanced stage (13). In such cases, systemic inflammation, metabolic dysregulation, and irreversible muscle wasting may reduce responsiveness to anabolic and appetite-stimulating agents (1, 14). Our results, together with previous evidence, suggest that earlier initiation, before severe weight loss and functional decline, could enhance the therapeutic benefits of anamorelin.
Furthermore, maintaining nutritional status and muscle mass is critical for continuing active cancer therapy. In our study, 69.0% of patients were receiving concomitant cancer treatment at anamorelin initiation, and improvements in appetite and nutritional indices may have contributed to treatment tolerance. Therefore, early intervention could support not only symptomatic improvement but also the broader goal of sustaining oncological treatment, which may ultimately impact survival outcomes.
Survival analysis revealed that the median overall survival was 17.9 months for patients with gastric cancer and 36.8 months for those with colorectal cancer. This is noteworthy considering the advanced disease stage and severity of cachexia at baseline. Larger prospective studies are needed to confirm whether early initiation of anamorelin can translate into a survival benefit.
The limitations of this study include its retrospective nature, small sample size, and single-center design. In addition, the timing of anamorelin initiation was not standardized, which may have influenced treatment outcomes. Nonetheless, our findings highlight the importance of initiating cachexia treatment earlier in the disease course, rather than delaying it until severe weight loss has occurred.
Anamorelin improved body weight, food intake, and nutritional status in patients with advanced gastrointestinal cancer cachexia, even when initiated at a later stage. However, the degree of recovery was modest, likely due to advanced cachexia at treatment initiation. These findings suggest that earlier administration, before substantial weight and muscle loss, may maximize therapeutic benefits, support the continuation of anticancer therapy, and potentially improve survival outcomes. Therefore, early intervention with anamorelin should be considered for the clinical management of cancer cachexia.
Acknowledgements
The Authors would like to thank Editage (www.editage.com) for the English language editing.
Footnotes
Authors’ Contributions
D.Y. and H.K. contributed to the conception and design of the study, data collection, data analysis, and manuscript writing. M.I, S.N., K.N., S.I., and H.O. contributed to providing critical revisions that were important for the intellectual content. T.M., K.Y., and T.M. contributed to the approving the version of the manuscript.
Conflicts of Interest
The Authors declare that they have no conflicts of interest in relation to this study.
Funding
No funding was received for the conduct of this study.
Artificial Intelligence (AI) Disclosure
No artificial intelligence (AI) tools, including large language models or machine learning software, were used in the preparation, analysis, or presentation of this manuscript.
- Received August 17, 2025.
- Revision received September 20, 2025.
- Accepted September 22, 2025.
- Copyright © 2025 The Author(s). Published by the International Institute of Anticancer Research.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
