Effects of adding a neurokinin-1 receptor antagonist to 5 mg olanzapine, a 5-hydroxytryptamine-3 receptor antagonist, and dexamethasone for preventing carboplatin-induced nausea and vomiting: a propensity score-matched analysis

BMC Cancer. 2022 Mar 23;22(1):310. doi: 10.1186/s12885-022-09392-9.

Abstract

Background: Olanzapine has been reported to be an effective antiemetic in patients receiving carboplatin-based chemotherapy. However, the efficacy of a neurokinin-1 receptor antagonist (NK1RA) added to olanzapine, a 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA), and dexamethasone (DEX) has not been proven. This study aimed to assess the efficacy and safety of NK1RA, in combination with three-drug antiemetic regimens containing olanzapine, in preventing nausea and vomiting induced by carboplatin-based chemotherapy.

Methods: Data were pooled for 140 patients receiving carboplatin-based chemotherapy from three multicenter, prospective, single-arm, open-label phase II studies that evaluated the efficacy and safety of olanzapine for chemotherapy-induced nausea and vomiting. The propensity score of the co-administration of NK1RA was estimated for each patient using a logistic regression model that included age, sex, and carboplatin dose. We analyzed a total of 62 patients, who were treated without NK1RA (non-NK1RA group: 31 patients) and with NK1RA (NK1RA group: 31 patients). The patients were selected using propensity score matching.

Results: The complete response rate (without emetic episodes or with no administration of rescue medication) in the overall period (0-120 h post carboplatin administration) was 93.5% in the non-NK1RA group and 96.8% in the NK1RA group, with a difference of -3.2% (95% confidence interval, -18.7% to 10.9%; P = 1.000). In terms of safety, there was no significant difference between the groups in daytime sleepiness and concentration impairment, which are the most worrisome adverse events induced by olanzapine.

Conclusions: The findings suggest that antiemetic regimens consisting of olanzapine, 5HT3RA, and DEX without NK1RA may be a treatment option for patients receiving carboplatin-based chemotherapy.

Keywords: 5-hydroxytryptamine-3 receptor antagonists; Antiemetics; Carboplatin; Dexamethasone; Nausea; Neurokinin-1 receptor antagonist; Olanzapine; Vomiting.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Carboplatin* / adverse effects
  • Dexamethasone / therapeutic use
  • Humans
  • Nausea* / chemically induced
  • Nausea* / drug therapy
  • Nausea* / prevention & control
  • Neurokinin-1 Receptor Antagonists* / therapeutic use
  • Olanzapine / therapeutic use
  • Propensity Score
  • Prospective Studies
  • Serotonin 5-HT3 Receptor Antagonists* / therapeutic use
  • Vomiting* / chemically induced
  • Vomiting* / drug therapy
  • Vomiting* / prevention & control

Substances

  • Neurokinin-1 Receptor Antagonists
  • Serotonin 5-HT3 Receptor Antagonists
  • Dexamethasone
  • Carboplatin
  • Olanzapine