A randomized, double-blind, placebo-controlled study evaluating the efficacy of combination olanzapine, ondansetron and dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving doxorubicin plus cyclophosphamide

Ann Palliat Med. 2019 Sep;8(4):372-380. doi: 10.21037/apm.2019.08.04. Epub 2019 Sep 2.

Abstract

Background: Since most of Thai cancer patients receiving high emetogenic chemotherapy do not have access to neurokinin-1 (NK-1) receptor antagonists or palonosetron as recommended by international guidelines for chemotherapy-induced nausea and vomiting (CINV) prevention. We decided to evaluate the efficacy of olanzapine with the real-life practice antiemetic drugs ondansetron and dexamethasone, in prevention of CINV resulting from doxorubicin plus cyclophosphamide regimen in early-stage breast cancer patients.

Methods: In this randomized, double-blind, placebo-controlled trial, we compared olanzapine with a placebo in combination with ondansetron and dexamethasone in early-stage breast cancer patients receiving doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2. The intervention group received olanzapine 10 mg orally while the control group received a matching placebo daily on day 1 through day 4. All patients received ondansetron 8 mg and dexamethasone 20 mg intravenously 30 minutes before chemotherapy administration and then dexamethasone 10 mg daily orally from day 1 through day 4. The primary endpoint was no nausea rate in the early period. The secondary endpoints were no nausea rate in the delayed and overall periods and a complete response (no vomiting and no use of rescue drug). Outcomes were determined by patients' self-reported daily records of episodes of vomiting or retching, use of rescue therapy and daily levels of nausea based on a visual-analogue scale from the first cycle of chemotherapy.

Results: A total of 39 female patients were randomized in a 1:1 ratio to receive olanzapine (20 patients) or a matching placebo (19 patients). A significantly greater proportion of patients reported no nausea in the olanzapine group than in the placebo group in both the early period (0-24 hours after chemotherapy) and the overall period (0-120 hours after chemotherapy). Patients who reported no nausea in the early period accounted for 50% and 10.5% in the olanzapine group and in the placebo group respectively (P=0.008). In the overall period, 30.0% and 0% of patients reported no nausea in the olanzapine and placebo groups respectively (P=0.009). In the early period, there was a significantly different complete response rate between two treatment groups; 75.0% in the olanzapine group and 36.8% in the placebo group (P=0.016). Overall treatment-related adverse events were not significantly different between the two study groups except that somnolence was significantly more common in the olanzapine group than in the placebo group.

Conclusions: Olanzapine 10 mg combined with ondansetron and dexamethasone was more effective than a placebo in preventing CINV resulting from doxorubicin plus cyclophosphamide in early-stage breast cancer patients, especially in the first 24 hours after chemotherapy administration. The short duration of olanzapine was safe and well tolerated.

Keywords: AC regimen; High-emetic chemotherapy regimen; antiemetic drugs; breast cancer; chemotherapy-induced nausea and vomiting (CINV); doxorubicin and cyclophosphamide; emetic evaluation.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antiemetics / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Breast Neoplasms / drug therapy
  • Cyclophosphamide / administration & dosage
  • Dexamethasone / therapeutic use*
  • Double-Blind Method
  • Doxorubicin / administration & dosage
  • Female
  • Humans
  • Middle Aged
  • Nausea / prevention & control*
  • Olanzapine / therapeutic use*
  • Ondansetron / therapeutic use*
  • Treatment Outcome
  • Vomiting / prevention & control*

Substances

  • Antiemetics
  • Ondansetron
  • Dexamethasone
  • Doxorubicin
  • Cyclophosphamide
  • Olanzapine