Efficacy and safety of 5 mg olanzapine combined with aprepitant, granisetron and dexamethasone to prevent carboplatin-induced nausea and vomiting in patients with gynecologic cancer: A multi-institution phase II study

Gynecol Oncol. 2020 Mar;156(3):629-635. doi: 10.1016/j.ygyno.2020.01.004. Epub 2020 Jan 9.

Abstract

Purpose: The aim of this study was to investigate the efficacy and safety of prophylactic administration of 5 mg olanzapine (OLZ) combined with neurokinin 1 receptor antagonist (NK1RA), 5-hydroxytryptamine type-3 receptor antagonist (5-HT3RA), and dexamethasone (DEX) to prevent nausea and vomiting in carboplatin (CBDCA) combination therapy for patients with gynecological cancer.

Methods: We conducted a single-arm, multi-institution, phase II study. Gynecological cancer patients scheduled to receive AUC ≥4 mg/mL/min CBDCA were enrolled. All patients received 5 mg OLZ (once daily after supper on days 1-4) combined with NK1RA, 5-HT3RA, and DEX. The primary end point was complete response (CR; no emesis and rescue therapy) during overall phase (120 h after the start of carboplatin administration).

Results: Between May 2018 and June 2019, 60 patients were enrolled from 3 institutions in Japan. A total of 57 patients who met the criteria were included in the efficacy and safety analysis. The CR rate for the overall phase was 78.9%. Acute (0-24 h) and delayed phases (24-120 h) were 96.5% and 80.7%, respectively. Somnolence was observed in 73.7% patients. However, somnolence of grade 2 or higher was observed in only 3.5% of cases. There were no grade 3 or 4 toxicities associated with OLZ.

Conclusions: Preventive use of OLZ combined with standard triplet therapy had promising activity with manageable safety, suggesting that this combination could be an effective standard treatment option for patients with AUC ≥4 mg/mL/min CBDCA combination therapy.

Keywords: Carboplatin; Gynecological cancer; Nausea; Olanzapine; Vomiting.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antiemetics / therapeutic use*
  • Aprepitant / therapeutic use
  • Carboplatin / administration & dosage
  • Carboplatin / adverse effects*
  • Dexamethasone / therapeutic use
  • Female
  • Genital Neoplasms, Female / drug therapy*
  • Granisetron / therapeutic use
  • Humans
  • Middle Aged
  • Nausea / chemically induced
  • Nausea / prevention & control*
  • Olanzapine / adverse effects
  • Olanzapine / therapeutic use*
  • Vomiting / chemically induced
  • Vomiting / prevention & control*

Substances

  • Antiemetics
  • Aprepitant
  • Dexamethasone
  • Carboplatin
  • Olanzapine
  • Granisetron