Olanzapine for Anorexia in Patients With Incurable Cancer and Cachexia (OlAnCa): A Double-Blind, Placebo-Controlled, Randomized Clinical Trial.

BACKGROUND

Pharmacologic options for managing anorexia in cancer cachexia are limited. This trial aimed to evaluate the efficacy of olanzapine in alleviating anorexia in patients with incurable cancer and cachexia.

METHODS

This double-blind, placebo-controlled, randomized trial included adult patients with incurable cancer and cachexia, scoring ≥4 on the Edmonton Symptom Assessment Scale (ESAS) anorexia item (ESAS-Anorexia) and <4 on the ESAS nausea item (ESAS-Nausea). A total of 164 patients were randomized in a 1:1 ratio to receive either placebo (n=82) or olanzapine 5 mg daily (n=82) for 4 weeks. The primary outcome was the change in ESAS-Anorexia score after 1 week. Secondary outcomes included changes in anorexia and quality of life scores, body weight, and handgrip strength after 4 weeks.

RESULTS

In the complete case analysis of the primary outcome (n=159; 97%), median [IQR] reduction in ESAS-Anorexia score after 1 week was significantly greater in the olanzapine group (-2 [-3 to 0] vs -1 [-2 to 0]; P=.003). The significance continued at 2 weeks (-2 [-4 to -1] vs -1 [-2 to 0]; P=.039). After 4 weeks, significantly more patients in the olanzapine group experienced >5% weight gain (14% vs 0%; P=.008), and the mean [SD] improvement in Functional Assessment of Anorexia/Cachexia Therapy - Anorexia/Cachexia Subscale score was higher (+2.7 [7.4] vs -0.04 [7]; P=.043). The mean [SD] decline in handgrip strength was greater with olanzapine and was significant in per-protocol analysis (-2.8 [4.9] kg vs -0.3 [4.1] kg; P=.027). Anxiety, insomnia, and nausea (P=.016, P=.034, and P=.039, respectively) were significantly less frequent with olanzapine, whereas grade ≥3 anemia and leukopenia were more frequent (P=.018 and P=.041, respectively).

CONCLUSIONS

A short course of olanzapine 5 mg daily significantly reduces anorexia in patients with incurable cancer and cachexia. Further studies are needed to evaluate its long-term safety and efficacy in cancer cachexia.