A New Treatment for Loss of Appetite in Cancer Patients: Low-Dose Olanzapine

Loss of appetite is an important problem in patients with cancer because malnutrition can affect their quality of life and response to treatment.

Loss of appetite in cancer patients can result from several factors. It may arise from a combination of the cancer itself, treatment methods, and psychological factors. Some causes include:

• Cancer cells: Cancer cells can consume the body's energy and nutrient resources and prevent normal cells from obtaining energy. They can also release substances called proinflammatory cytokines, causing loss of appetite and weight loss.
• Treatment methods: Cancer treatments such as chemotherapy, radiotherapy, immunotherapy, hormonal therapy, and surgery can have side effects that reduce appetite. These may include gastrointestinal problems such as nausea, vomiting, mouth sores, and changes in taste.
• Psychological factors: Cancer diagnosis and treatment can lead to emotional problems such as stress, anxiety, and depression, which can reduce appetite and cause weight loss.

The prevalence of appetite problems in cancer patients varies according to cancer type, stage, treatment methods, and general health. Approximately 40% to 80% of patients experience nutritional problems such as loss of appetite and weight loss.

Various approaches are used to improve appetite in cancer patients. Their effectiveness depends on the patient's condition and treatment:

• Medications: Appetite stimulants can help support appetite and weight gain. Drugs such as megestrol acetate (Megace and Borea) and dronabinol are used to stimulate appetite and reduce weight loss.
• Nutritional support: Cancer patients can be offered foods specially prepared to meet their energy and nutrient needs. Dietitians determine an appropriate diet and provide nutritional advice.
• Physical activity: Light physical activity can improve appetite and increase energy levels. Activities should be selected according to the patient's condition.

Megestrol acetate is the most commonly preferred appetite stimulant for cancer patients. It is a synthetic hormone derived from progesterone. Its appetite-stimulating effect occurs through mechanisms regulating hunger and fullness signals in the hypothalamus. However, it can cause side effects such as blood clots, hormonal disturbances, adrenal suppression with prolonged use, and Cushing syndrome. New treatments with the potential to regulate appetite in cancer are therefore being investigated.

Low-Dose Olanzapine May Improve Appetite in Patients Receiving Chemotherapy

Taking 2.5 mg of olanzapine (Zypexa and other brands) daily was observed to significantly improve appetite in patients receiving chemotherapy for locally advanced or metastatic gastric, hepatobiliary, and lung cancers.

Lakshmi Sandhya and colleagues at the Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) in Puducherry, India, explain the importance of this issue: "Anorexia is a condition we see in approximately 50% of newly diagnosed cancer patients and can have serious effects on survival. Patients with lung and gastrointestinal cancers are particularly prone to appetite loss during chemotherapy. Olanzapine is a proven appetite stimulant and is used as a short-term antiemetic (a drug affecting the vomiting center) in cancer patients, but its use for long-term appetite stimulation has not yet been sufficiently studied."

Journal of Clinical Oncology published the study on March 28, 2023. The researchers designed a study in which 124 previously untreated adults (aged 18 or older) with locally advanced or metastatic gastric, hepatobiliary, or lung cancer, with a median age of 55, received 2.5 milligrams of olanzapine or placebo for 12 weeks.

Alongside changes in nutritional status, quality of life, and chemotherapy side effects, the main outcomes of interest were weight gain of more than 5% and improved appetite based on a visual analog scale (VAS) and questionnaires.

After 12 weeks, definitive results were available for 58 patients in the olanzapine group and 54 in the placebo group. Of these, 60% in the olanzapine group and 9% in the placebo group achieved the desired outcome of more than 5% weight gain.

In addition, 52% of the olanzapine group versus 18% of the placebo group consumed more than 75% of their recommended daily calorie intake.

Most reported side effects were similar between groups (85% with olanzapine versus 88% with placebo), and no changes in blood parameters were observed.

The proportion of patients with grade 3 or higher side effects was lower in the olanzapine group than in the placebo group (12% versus 37%). Patients in the olanzapine group reported significantly improved quality of life from baseline compared with placebo patients.

The researchers noted several limitations, including the range of cancers and treatment regimens, missing weight data after 12 weeks, the relatively small study population, and the subjective nature of anorexia measurements.

In conclusion, low-dose olanzapine may be an effective and well-tolerated additional intervention for patients at risk of anorexia when starting chemotherapy. Future studies could include more patients with a variety of cancers and assess long-term outcomes such as survival.