The Balance Between the Effectiveness and Safety for Chemotherapy-Induced Nausea and Vomiting of Different Doses of Olanzapine (10 mg Versus 5 mg): A Systematic Review and Meta-Analysis

Abstract

IntroductionThe aim of this study is to rigorously review the efficacy and safety of olanzapine in chemotherapy-induced nausea and vomiting (CINV) settings including (1) at 5- and 10-mg doses, and (2) the setting of highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC).MethodsEmbase, Pubmed, and Cochrane Library were searched from the establishment of the database through April 18, 2021. The primary efficacy endpoints were the rate of complete response (CR; no emesis and no rescue), in the acute (0–24 h post-chemotherapy), delayed (24–120 h post-chemotherapy), and overall (0–120 h post-chemotherapy) phases. The secondary efficacy endpoints were the rates of complete control (CC, no nausea, and no emesis), for each phase. Safety endpoints were the rate of somnolence, as assessed by Common Terminology Criteria for Adverse Events (CTCAE) criteria. The Mantel–Haenszel, random, or fixed-effect analysis model was used to compute risk ratios and accompanying 95% confidence intervals for each endpoint. For endpoints that statistically favored one arm, absolute risk differences were computed to assess whether there is a 10% or greater difference, used as the threshold for clinical significance by MASCC/ESMO.ResultNine studies reported the use of 10 mg olanzapine to prevent CINV; three studies reported the use of 5 mg olanzapine to prevent CINV. When olanzapine was administered at 10 mg for HEC patients, the six endpoints were statistically and clinically better than the control group. For MEC patients, four out of six endpoints were better than the control group. When olanzapine is administered at 5 mg for MEC patients, four endpoints have statistical and clinical advantages. The sedative effects of 10 and 5 mg olanzapine were statistically more significant than those of the control group. The sedative effect of the 10-mg olanzapine group was more significant than that of the 5-mg olanzapine group, both statistically and clinically.Conclusion5 mg olanzapine may be as effective as 10 mg olanzapine for patients with HEC and MEC, and its sedative effect is lower than 10 mg olanzapine. Fewer studies on 5 mg olanzapine have led to uncertain data. In the future, more randomized controlled trials of 5 mg olanzapine are needed to study the balance between the effectiveness and safety of olanzapine.

Dexamethasone-Free Antiemetic Prophylaxis for Highly Emetogenic Chemotherapy: A Double-Blind, Phase III Randomized Controlled Trial (CINV POD study)

“…Therefore, we used a 5-mg olanzapine dose in our study. 34 The study was not intended to compare DEX with fosaprepitant. Our objective was to determine whether a three-drug antiemetic regimen without DEX was equally effective when compared with a standard three-drug regimen that included DEX.…”

“… 17 , 35 However, using higher doses of DEX and olanzapine is associated with more adverse events. 4 , 34 …”

Olanzapine for the Prevention and Treatment of Chemotherapy-Induced Nausea and Vomiting: A Review to Identify the Best Way to Administer the Drug

“…Similarly, 153 patients who received cisplatin were enrolled in a phase II clinical study conducted by Takako; the results showed that the CR for delayed period was 78% (80% CI: 70.3–83.8, p = 0.01) in the 10 mg olanzapine group and 86% (80% CI: 79.2–90.7, p < 0.001) in the 5 mg olanzapine group; incidence of somnolence was 53.3% and 45.5%, respectively [ 33 ]. This also suggests that both 10 mg and 5 mg of olanzapine significantly improved delayed vomiting, dramatically reduced the frequency and duration of nausea in high-risk patients, and 5 mg olanzapine causes less somnolence [ 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ].…”

“…This suggests that olanzapine is more effective than metoclopramide in controlling breakthrough CINV among patients with HEC, and it may become an effective antiemetic drug for breakthrough CINV [ 25 ]. In addition, no grade 3 or 4 toxicity was observed in phase III trials of olanzapine at 5–10 mg, before and 3–4 days after chemotherapy [ 26 , 27 , 28 , 29 ]. Specifically, there was no significant dizziness, drowsiness, extrapyramidal reactions, or cathisophobia.…”

Prevention and management of acute toxicities from conditioning regimens during hematopoietic stem cell transplantation

“…Recent studies have suggested that, when compared to a 10mg dose, a 5mg dose of olanzapine resulted in similar control of CINV and oftentimes was associated with less sedation. [11][12][13][14]…”