Effect of multimodal intervention care on cachexia in patients with advanced cancer compared to conventional management (MIRACLE): an open-label, parallel, randomized, phase 2 trial

Abstract

Background Cancer cachexia (CC) is a multifactorial process characterized by progressive weight loss, muscle mass, and fat tissue wasting, which adversely affects the quality of life and survival of patients with advanced stages of cancer. CC has a complex and multifactorial pathophysiology, and there is no established standard treatment. Therefore, it is often irreversible and a single treatment modality is unlikely to suppress its progression. We are conducting a randomized trial to investigate the efficacy and safety of a multimodal intervention compared to the best supportive care for patients who received palliative chemotherapy. Methods Patients with lung or gastrointestinal cancers undergoing palliative chemotherapy are eligible. Patients are randomized into a multimodal intervention care (MIC) arm versus a conventional palliative care (CPC) arm. MIC includes ibuprofen, omega-3-fatty acid, oral nutritional supplement, weekly physical, psychiatric assessment, nutritional counseling, and complementary and alternative medicine. CPC includes basic nutritional counseling and megestrol acetate as needed (i.e., anorexia ≥ grade 2). All interventions are performed for 12 weeks per subject. The co-primary outcomes are change (kg) in total lean body mass and handgrip strength (kg) from the baseline. A total of 112 patients will be assigned to the two arms (56 in each group). Discussion The purpose of this study is to evaluate the effect of MIC in preventing or alleviating CC in patients who underwent palliative chemotherapy. As there is no established single treatment for CC, it is expected that the results of this clinical trial will provide new insights to significantly improve the quality of life of patients with cancer. Considering the complex mechanisms of cachexia, the effect of MIC rather than a single specific drug is more promising. In this study, we did not overly restrict the type of cancer or chemotherapy. Therefore, we attempted to measure the effects of complex interventions while preserving clinical situations. Thus, it is expected that the results of this study can be applied effectively to real-world practice. Trial registration This clinical trial was registered in the Clinical Research Information Service (KCT0004967), Korean Clinical Trial Registry on April 27, 2020, and ClinicalTrial.gov (NCT 04907864) on June 1, 2021.

Exercise-based interventions for cancer cachexia: A systematic review of randomised and non-randomised controlled trials

“…The last focuses on exercise with psychoeducational support. The target sample size for each study is 30, 20, 112, and 130 patients respectively, 39 , 40 , 41 , 42 hence these offer strong potential to progress this field with more robust evidence.…”

Cancer cachexia – adopting a systems wide approach

“…However, cachexia is recognized as a multisystem syndrome affecting multiple organ systems and causing a wide range of clinical effects. Indeed, consensus is growing that the management of cancer cachexia should reflect this, with multimodal treatment, combining targeted anabolic therapies, antiinflammatories, nutritional supplementation, exercise and treatment of secondary factors advocated [1,2,44]. This is reflected in recent clinical practice guidelines, which recognize the complexity of causes contributing to weight loss in cancer patients and prioritize multimodal care [2].…”

Non‐steroidal anti‐inflammatory drugs for treatment of cancer cachexia: A systematic review

“…Studies in the field of CC treatment are shifting towards multi‐component interventions, based on the principle that one intervention alone is not sufficient to combat CC 3 and that there may be cumulative or synergistic effects between components. NSAIDs have been included in many of these, 17 , 18 , 19 , 20 despite the lack of robust evidence for their efficacy and safety in this population.…”

“…While the search strategies and eligibility criteria differed between these reviews, both concluded that, while there was some evidence of beneficial effects, it was not sufficient to recommend the use of NSAIDs for clinical management of CC outside of clinical trials. However, many recent clinical trials of multi‐component CC interventions have included NSAIDs as a core component 17–20 . Thus, an up‐to‐date assessment of the evidence for NSAIDs in the treatment of CC is required.…”

“…However, many recent clinical trials of multi‐component CC interventions have included NSAIDs as a core component. 17 , 18 , 19 , 20 Thus, an up‐to‐date assessment of the evidence for NSAIDs in the treatment of CC is required. This review provides this, as well as a broader range of patient‐centred outcomes, and a risk of bias assessment amongst included studies, which was not produced in the previous reviews.…”