A randomized trial of individualized versus standard of care antiemetic therapy for breast cancer patients at high risk for chemotherapy-induced nausea and vomiting

Abstract

Purpose Despite triple antiemetic therapy use for breast cancer patients receiving emetogenic chemotherapy, nausea remains a clinical challenge. We evaluated adding olanzapine (5 mg) to triple therapy on nausea control in patients at high personal risk of chemotherapy-induced nausea and vomiting (CINV). Methods This multi-centre, placebo-controlled, double-blind trial randomized breast cancer patients scheduled to receive neo/adjuvant chemotherapy with anthracycline-cyclophosphamide or platinum-based chemotherapy to olanzapine (5 mg, days 1–4) or placebo. Primary endpoint was frequency of self-reported significant nausea, repeated for all cycles of chemotherapy. Secondary endpoints included: duration of nausea, overall total control of CINV, Health Related Quality of Life (HRQoL) using FLIE questionnaire, use of rescue mediation and treatment-related adverse events. Results 218 eligible patients were randomised to placebo (105) or olanzapine (113). From days 0–5 following each cycle of chemotherapy, 41.3% (95%CI: 36.1–46.7%) of patients in the placebo group reported significant nausea compared to 27.7% (95%CI: 23.2–32.4%) in the olanzapine group (p = 0.001). Across all cycles of chemotherapy, patients receiving olanzapine experienced a statistically significant improvement in HRQoL (p < 0.001). Grade 1/2 sedation was the most commonly side effect reported at 40.8% in the placebo group vs. 54.1% with olanzapine (p < 0.001). Conclusion In patients at high personal risk of CINV, the addition of olanzapine 5 mg daily to standard antiemetic therapy significantly improves the control of nausea, HRQoL, with no unexpected toxicities.

The Efficacy of Olanzapine-Contained Antiemetic Therapy for Breast Cancer Patients: A Systematic Review and Pooled Analysis

“…During the overall period, the complete cycle response was 41.8% in the olanzapine group versus 32.4% in the control group following each cycle of chemotherapy. In addition, in terms of overall nausea control, olanzapine signi cantly decreased the rate from 41.3-27.7% [9]. Complete response rates were contradictory among the eligible retrospective studies.…”

“…However, low dose olanzapine was well tolerated and did not markedly increase the incidences of body weight, fatigue, somnolence, and anorexia. In Clemons' s study, the rate of grade 1-2 sedation was increased from 40.8-54.1%, and more extrapyramidal symptoms were observed in the olanzapine group [9]. Overall, based on published clinical studies, adding olanzapine to standard antiemetic therapy is safe and bene cial.…”

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

“…Twelve studies are reasonably excluded—five studies ( 16 – 20 ) only have Conference abstract, five studies ( 21 – 25 ) do not have specific experimental results, and two studies ( 26 , 27 ) are unclear in method. A total of 12 studies ( 28 – 41 ) have eligibility criteria for systematic evaluation. All of these studies have been published in peer-reviewed journals.…”

“…Eleven studies ( 28 – 34 , 36 – 39 ) are randomized controlled experiments; one study ( 35 )is a prospective control study; and nine studies ( 28 – 31 , 33 , 34 , 37 – 39 ) compared 5 or 10 mg olanzapine with placebo, while three studies ( 32 , 35 , 36 ) compared the four-drug regimen with standard regimen; and 12 studies differed in the drugs used in the concurrent antiemetic regimens: a corticosteroid, 5-HT3 receptor antagonist, and NK1 receptor antagonist in seven studies ( 28 – 32 , 36 , 39 ) and a corticosteroid and 5-HT3 receptor antagonist in five studies ( 33 – 35 , 37 , 38 ).…”

“…All studies are CINV for adults. Nine studies ( 31 – 39 ) reported the use of 10 mg olanzapine to prevent CINV; three studies ( 28 – 30 , 40 , 41 )reported the use of 5 mg olanzapine to prevent CINV; five studies ( 31 , 32 , 37 – 41 ) included HEC patients; two studies ( 29 , 33 )included MEC patients; and five studies ( 28 , 30 , 34 – 36 )included HEC and MEC patients. Of the five studies involving both HEC and MEC, only three studies ( 34 – 36 ) reported the results of HEC and MEC separately, and two studies were not enough for subgroup analysis; eight studies ( 28 , 29 , 31 – 35 , 37 ) reported adverse reactions including sedation, Table 2 provides the procedures of each study to evaluate the sedative effect of olanzapine; 11 studies ( 28 – 34 , 36 – 39 ) are randomized controlled experiments; 1 study ( 35 ) is a prospective control study ( 40 , 41 ); 9 studies used a double-blind placebo-controlled approach; and 3 studies ( 32 , 35 , 36 ) were unclear on blind methods.…”