Hepatocellular Carcinoma
Conditions
Keywords
inflammation, cachexia, eicosapentaenoic acid, lipid mediator
Brief summary
Dietary intervention with eicosapentaenoic acid combined with chemotherapy may shift inflammatory mediators toward resolution in non-resectable hepatocarcinoma and help to preserve muscle mass.
Detailed description
Cancer-associated cachexia is a debilitating and potentially life-threatening syndrome characterized by progressive loss of body weight, skeletal muscle, and adipose tissue, leading to functional impairment and reduced response to oncologic therapy. It is driven in part by systemic inflammation and increased pro-inflammatory cytokines, and it cannot always be reversed with conventional support. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid (PUFA), has anti-inflammatory properties and is rapidly incorporated into cell membranes, modulating lipid mediator pathways. EPA supplementation may help to attenuate systemic inflammation, alleviate cachexia symptoms, and promote the production of specialized pro-resolving mediators. A daily dose of 3 grams appears sufficient to achieve maximal incorporation into cell membranes without significant adverse events. Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide, with most patients diagnosed at advanced stages. Cachexia is common in advanced HCC and contributes to functional decline, increased treatment toxicity, and poorer outcomes. Preclinical studies suggest that omega-3 PUFAs may also exert anti-tumor effects through modulation of COX-2 and Wnt/beta-catenin signaling pathways. For these reasons, in this proposal, the investigators aim to determine wheter supplementation with EPA in combination with chemotherapy will modify the blood profile of pro-inflammatory and pro-resolving mediators, promoting the resolution of inflammation associated with HCC, and, in turn, mitigate muscle mass loss during oncologic treatment.
Interventions
DIETARY_SUPPLEMENTEicosapentaenoic acid oral lipidic emulsion
1 sachet/day of 20 ml containing 3g EPA during 12 weeks
DIETARY_SUPPLEMENTPacebo oral lipidic emulsion
1 sachet/day of 20 ml of placebo during 12 weeks
Sponsors
Instituto de Investigación Sanitaria Aragón
Hospital Clínico Universitario Lozano Blesa
Solutex GC S.L.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
The statistician responsible for analysing the data was also blinded. Only the nurse in charge of recruiting participants and releasing the products was non-blinded.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Participants diagnosed with unresectable HCC, candidates for systemic treatment with Sorafenib or similar agents. * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. * Life expectancy \> 8 weeks. * Not eligible for curative treatment (surgical resection/ablative therapy/liver transplantation). * Not having a history of previous or concomitant malignancy except when a disease-free interval \> 5 years had been documented. * Not receiving any other systemic antitumor agents (docetaxel, doxorubicin, irinotecan).
Exclusion criteria
* Allergy to omega-3 acid or fish-derived products. * Psychological or medical conditions that can interfere with study participation or the ability to provide informed consent. * Drug abuse (except for alcohol). * Any experimental therapy within 30 days prior to study entry. * Recurrent epistaxis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of EPA supplementation on muscle mass | At baseline, and at 12 weeks (study completion) | Muscle mass is assessed by calculating the skeletal muscle index using computed tomography, based on a single axial slice at the L3 level. The SliceOmatic software (TomoVision) is used for the calculations. Sarcopenia is evaluated using two criteria: Carey reference values for end-stage liver disease patients awaiting transplantation, and Martin reference values for oncology patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evolution of nutritional status. | At baseline, at 6 weeks, and at 12 weeks (study completion) | Nutritional status is assessed using the validated Patient-Generated Subjective Global Assessment tool (PG-SGA, Bauer 2002) that classify patients as well nourished (A), moderately malnourished or at risk of malnutrition (B), or severely malnourished (C). |
| Effect of EPA supplementation on quality of life assessed using the EORTC-QLQ-30. | At baseline, at 6 weeks, and at 12 weeks (study completion) | Quality of life is assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-30) |
| Change in the quality of life assessed using the EORTC-QLQ-HCC18. | At baseline, at 6 weeks, and at 12 weeks (study completion) | Quality of life is assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Hepatocellular Carcinoma 18-question module (QLQ-HCC18). |
| Effect of EPA supplementation on plasma and serum profiles of pro-inflammatory and pro-resolving lipid mediators. | At baseline, and at 12 weeks (study completion) | Plasma and serum concentrations of pro-inflammatory and pro-resolving lipid mediators derived from polyunsaturated fatty acids are determined using targeted LC-MS/MS. |
| Change in C-reactive protein (CRP) concentration upon supplementation. | At baseline, and at 12 weeks (study completion) | The C-reactive protein is measured using an immunoturbidimetric assay following the standard laboratory methods in the Hospital Clínico Universitario Lozano Blesa. |
| Change in interleukin 6 upon supplementation. | At baseline, and at 12 weeks (study completion) | Plasma IL-6 levels are determined by enzyme-linked immunosorbent assay. |
| Change in interleukin 8 upon supplementation. | At baseline, and at 12 weeks (study completion) | Plasma Il-8 is quantified using the Human XL Cytokine Luminex® Kit Performance Assay (R\&D Systems). |
| Change in interferon gamma (IFNγ) upon supplementation. | At baseline, and at 12 weeks (study completion) | Plasma IFNγ is quantified using the Human XL Cytokine Luminex® Kit Performance Assay (R\&D Systems). |
| Change in the neutrophil-to-lymphocyte ratio (NLR) upon supplementation. | At baseline, and at 12 weeks (study completion) | NLR is calculated by dividing the absolute neutrophil count by the absolute lymphocyte count obtained from peripheral blood samples. Both values were derived from the complete blood count (CBC) analysis. |
Countries
Spain
Contacts
PRINCIPAL_INVESTIGATORAngel Lanas Arbeloa, MD, PhD
University Hospital Lozano Blesa. IIS Aragón. CIBER de Enfermedades Hepáticas y Digestivas
Outcome results
None listed