A Nutrition and Exercise Program With Olanzapine Compared to Olanzapine Alone: A Trial in Patients With Advanced Tumors

Cancer-related malnutrition represents a major clinical challenge. It is characterized by involuntary weight loss, muscle wasting, functional decline, reduced quality of life (QoL), longer and more frequent hospitalizations, and an increased risk for complications. Together, these factors substantially increase healthcare costs.

Despite growing awareness, evidence from robust randomized trials on multimodal interventions remains limited. Effective management requires a coordinated, multidisciplinary, and multimodal strategy.

The combination of nutritional counseling, physical exercise, and olanzapine (an ASCO-recommended appetite stimulant used according to standard care) may synergistically improve QoL (primary endpoint; Functional Assessment of Cancer Therapy - General; FACT-G), as well as nutritional status, energy intake, fatigue, muscle mass, and strength (secondary endpoints) in patients with advanced cancer.

With this prospective, randomized controlled trial, we aim to investigate whether adding a structured nutrition and exercise intervention to olanzapine improves QoL after 12 weeks of the program, compared to olanzapine alone.

Eligible outpatients with metastatic or locally advanced solid tumors and appetite loss will be randomized to either:

• an intervention group receiving personalized nutrition counseling and a physical exercise program, in combination with a leucine and β-hydroxy β-methylbutyrate (HMB)-enriched whey protein supplement; or
• a control group receiving standard oncological care.

All participants will receive low-dose olanzapine for the treatment of appetite loss according to standard clinical care, with treatment initiated after the baseline assessment at the start of the 12-week program.

Both arms will be assessed at baseline (0 weeks), after the 12-week intervention phase, and at a follow-up assessment after 24 weeks.

Inclusion criteria

• Age ≥18 years
• Metastatic or locally advanced solid tumors, excluding lymphoma, not eligible for curative treatment
• VAS score ≤70 for appetite, as defined for anorexia in oncology patients (olanzapine is prescribed according to clinical guidelines as part of standard care)
• WHO-PS of ≤3
• Ability to participate in physical exercise, as judged by the treating oncologist
• Anticipated life expectancy of at least six months
• Willingness to provide written informed consent

Exclusion criteria

• Pregnancy or breastfeeding
• Parkinson's disease, known risk for narrow-angle glaucoma, or any other contraindication to olanzapine, as judged by the treating oncologist
• Alcohol consumption >2 units/d
• Use of Olanzapine for any indication for more than four days per month
• Current use of any antipsychotic or antidepressant medication
• Recent use of systemic corticosteroids (prednisolone ≥10 mg/d or equivalent) for more than seven days within the past four weeks
• Presence of ascites at time of enrolment
• Concurrent radiotherapy to the esophagus
• Intake of products with added high-dose BCAA (branched-chain amino acids, total ≥3 g/d) within the past month
• Tube feeding and/or parenteral nutrition within the previous month (excluding ONS (oral nutritional supplements)
• History of ileus within the past month
• Allergy to milk protein
• Inability to comprehend trial information due to language barriers, cognitive or psychological limitations, or disease-related factors