Olanzapine Use Aids in the Management of Cytotoxic Chemotherapy-Induced Anorexia

Olanzapine may be an inexpensive way to manage anorexia in patients receiving cytotoxic chemotherapy, according to data from a randomized clinical trial (CTRI/2020/08/027133) published in the Journal of Clinical Oncology. The findings demonstrated that patients receiving olanzapine experienced improvements in weight loss, appetite, and nutrition scores.

Following 12 weeks of treatment, the percentage of patients who received olanzapine (n = 58) and gained at least 5% of their body weight was 60%. Conversely, the percentage of patients who gained at least 5% on placebo (n = 54) was 9%. The proportion of patients struggling with weight loss at the end of the study period was 14% vs 59%, respectively. Patients receiving olanzapine experienced a mean weight increase of 52.1 kg to 55.7 kg and those receiving placebo experienced a mean weight decrease of 52.5 kg to 51.7 kg.

Patients receiving olanzapine also experienced significant improvements in appetite by week 12. By the end of treatment, 22% of patients in the olanzapine group had achieved Functional Assessment of Chronic Illness Therapy system of Quality-of-Life questionnaires Anorexia Cachexia subscale (FAACT ACS) scores greater than 37; only 4% of patients receiving placebo achieved the same scores (P = .004). The percentage of patients who reported appetite increases were 43% vs 13%, respectively (P < .001).

Forty-three percent and 9% of patients in the olanzapine and placebo group, respectively, experienced nutrition score improvements (P < .0001). The percentage of patients who could consume 75% of their required calories and protein was 52% vs 18%, respectively (P < .0001). Lastly, quality-of-life (QOL) improvements from baseline were reported in 70% of patients in the olanzapine group, and 50% of patients in the placebo group (P < .003).

“Olanzapine demonstrated stimulation of appetite and better oral intake in patients receiving chemotherapy,” Lakshmi Sandhya, MD, of the Department of Medical Oncology at the Jawaharlal Institute of Postgraduate Medical Education and Research, in Puducherry, India, and co-investigators, wrote in the study. “This resulted in a more significant proportion of patients achieving weight gain during therapy.”

“Since olanzapine is inexpensive and well-tolerated, we believe that olanzapine can be considered an add-on therapy in patients starting chemotherapy who are at risk of developing anorexia in all centers,” they added.

The study included patients of age 18 years or older with newly diagnosed, locally advanced or metastatic gastric, hepatopancreaticbiliary (HPB), or lung cancer who were set to receive their first cycle of cytotoxic chemotherapy. Patients could have an ECOG performance status of 0 to 3, and they needed to be able to consume an oral diet. Per the antiemetic policy at the center, all patients received short duration olanzapine (5 mg once daily for days 1 through 4) and steroids.

Patients receiving long-term steroids, or antipsychotics were not eligible for the study, nor were patients receiving lose-dose, oral, metronomic chemotherapy. Those receiving tyrosine kinase inhibitors alone (without cytotoxic chemotherapy) were also ineligible.

Patients randomly assigned to the intervention cohort were prescribed 2.5 mg olanzapine daily for 12 weeks; those randomly assigned to the control arm received placebo. All patients received an individualized diet sheet highlighting the importance of a high-calorie, high-protein, nutrient-dense, and healthy diet. The diet sheet emphasized home-based foods, and did not advise or recommended nutritional supplements, because many patients were coming from lower income backgrounds.

The intervention began on the first day of cycle 1 of chemotherapy. Patients were assessed at baseline, during each visit for chemotherapy cycles, and at the end of the study. Investigators recorded the following parameters: weight, height, body mass index, mid-arm circumference, and triceps skin fold-thickness. They also used the subjective global assessment tools to document their nutritional status and the 24-hour dietary recall was used to calculate the calorie and protein deficit. Questionnaires were leveraged to assess function and QOL.

The trial ultimately screened 150 patients and enrolled 124. The baseline clinical characteristics were similar between the experimental and control cohorts. The median age was 55 years, and two-thirds of the participants were men. The most common histology was gastric cancer (55%), followed by lung cancer (35%). Moreover, 84% of patients had stage IV disease, and were also receiving palliative treatments. The proportion of patients undergoing highly emetogenic and moderately emetogenic chemotherapies between the 2 arms were similar (23% vs 25% and 77% vs 75%, respectively).

In addition, clinicians could choose to modify the chemotherapy dose for poor performance or poor nutrition status. As a result, 37% (n = 23) and 34% (n = 21) of patients in the olanzapine and placebo groups, respectively, began at a reduced dose of chemotherapy.

At baseline, almost all patients were anorexic and most met approximately 5% of the recommended daily caloric intake. Further, more than half of the patients reported weight loss of greater than 5% from their weight precancer diagnoses in both the olanzapine and placebo groups (57% vs 59%, respectively). Approximately 75% of the patients had below average or poor QOL measures at baseline as well.

Of note, chemotherapy tolerance was deemed to be significantly better in the olanzapine group. The percentage of patients who required dose modifications in their second cycle was 28% and 39% in the experimental and control arm, and the percentage of patients who had a dose increase was 75% vs 14%.

Regarding safety, most toxicities were nonhematologic and equally distributed between the arms (85% vs 88%). The proportion of grade 3 or greater toxicities were lower in the intervention arm (12% vs 37%; P = .002).

A limitation of this study was the inclusion heterogeneous cancer subtypes. The study period also only lasted 12 weeks and longer-term sustainability was not assessed. Moreover, 112 patients were eligible for final analysis, and anorexia is notably difficult to objectively measure—although investigators leveraged weight gain and nutrition scores to be as objective as possible.

The authors noted that, despite these limitations, the demonstrated calorie intake, better nutritional status, weight gain, and reduced chemotherapy toxicity in patients receiving olanzapine make a strong case for considering olanzapine for those patients at risk of anorexia.

Reference

Sandhya L, Devi Sreenivasan N, Goenka L, et al. Randomized double-blind placebo-controlled study of olanzapine for chemotherapy-related anorexia in patients with locally advanced or metastatic gastric, hepatopancreaticobiliary, and lung cancer. J Clin Oncol. Published online March 28, 2023. doi:10.1200/JCO.22.01997