Randomized Double-Blind Placebo-Controlled Study of Olanzapine for Chemotherapy-Related Anorexia in Patients With Locally Advanced or Metastatic Gastric, Hepatopancreaticobiliary, and Lung Cancer

Abstract

PURPOSE Anorexia occurs in 30%-80% of patients with advanced malignancies, which may be worsened with chemotherapy. This trial assessed the efficacy of olanzapine in stimulating appetite and improving weight gain in patients receiving chemotherapy. METHODS Adults (≥18 years) with untreated, locally advanced, or metastatic gastric, hepatopancreaticobiliary (HPB), and lung cancers were randomly assigned (double-blind) to receive olanzapine (2.5 mg once a day for 12 weeks) or placebo along with chemotherapy. Both groups received standard nutritional assessment and dietary advice. The primary outcomes were the proportion of patients with weight gain > 5% and the improvement in appetite (assessed by the visual analog scale [VAS] and the Functional Assessment of Chronic Illness Therapy system of Quality-of-Life questionnaires Anorexia Cachexia subscale [FAACT ACS]). Secondary end points were change in nutritional status, quality of life (QOL), and chemotherapy toxicity. RESULTS We enrolled 124 patients (olanzapine, 63 and placebo, 61) with a median age of 55 years (18-78 years), of whom 112 (olanzapine, 58 and placebo, 54) were analyzable. The majority (n = 99, 80%) had metastatic cancer (gastric [n = 68, 55%] > lung [n = 43, 35%] > HPB [n = 13, 10%]). The olanzapine arm had a greater proportion of patients with a weight gain of > 5% (35 of 58 [60%] v 5 of 54 [9%], P < .001) and improvement in appetite by VAS (25 of 58 [43%] v 7 of 54 [13%], P < .001) and by FAACT ACS (scores ≥37:13 of 58 [22%] v 2 of 54 [4%], P = .004). Patients on olanzapine had better QOL, nutritional status, and lesser chemotoxicity. Side effects attributable to olanzapine were minimal. CONCLUSION Low-dose, daily olanzapine is a simple, inexpensive, well-tolerated intervention that significantly improves appetite and weight gain in newly diagnosed patients on chemotherapy.

Mirtazapine as Appetite Stimulant in Patients With Non–Small Cell Lung Cancer and Anorexia

“…Furthermore, mirtazapine had a positive effect in global health status at 8 weeks, HADS score, and functional scales, especially cognitive functioning, which could be inferred as a positive effect of better energy intake similar to the findings reported with olanzapine. 18 A multidisciplinary management including regular nutritional care in addition to the use of appetite stimulants like mirtazapine represents a crucial and revolutionary scheme of treatment for cancer-associated anorexia palliation. We suggest that therapeutic options to increase appetite, energy intake, and body weight need to be individualized according to catabolic state, muscle reserve, benefit and risk evaluation along with psychiatric and nutritional surveillance.…”

“…Based on the findings of this study, mirtazapine is a feasible and safe option to add as a nutritional intervention in patients with advanced NSCLC with anorexia given its benefit in energy intake including high-quality macronutrients, considering that increased energy intake is the first step to stop unintentional weight loss and stability or increase of body weight. Furthermore, mirtazapine had a positive effect in global health status at 8 weeks, HADS score, and functional scales, especially cognitive functioning, which could be inferred as a positive effect of better energy intake similar to the findings reported with olanzapine . A multidisciplinary management including regular nutritional care in addition to the use of appetite stimulants like mirtazapine represents a crucial and revolutionary scheme of treatment for cancer-associated anorexia palliation.…”

“…One of the primary outcomes of this study was improvement in appetite, which has been selected previously as an end point and it is also among the main indications for which mirtazapine can be prescribed. 12,[15][16][17][18] Of note, studies on this topic reported appetite by heterogeneous tools that complicates its interpretation. In the present study, we used a validated questionnaire to be more objective to significantly identify appetite loss/changes.…”

Loss of appetite in patients with cancer: an update on characterization, mechanisms, and palliative therapeutics

“…First, Sandhya and others conducted a randomized, double-blinded trial to test olanzapine. Smaller prior studies had suggested this agent, which is now used routinely to prevent chemotherapy-induced nausea and vomiting, would be effective for treating anorexia in patients with cancer 13▪▪ . Thus, these investigators enrolled 124 patients with gastrointestinal cancers and anorexia and randomly assigned each in a 1:1 manner to olanzapine 2.5 mg orally per day versus placebo.…”

Reply to H. Onishi et al

“…We thank Onishi et al 1 for their interest in our article. 2 The authors highlighted the problem of akathisia, a potential side effect of olanzapine. Studies of olanzapine as an antipsychotic agent (usual doses ranging from 10 to 20 mg once daily) have reported akathisia in 3%-16% of patients, 3 but these side effects are generally mild and rarely require treatment.…”