Efficacy and safety of olanzapine combined with aprepitant, palonosetron, and dexamethasone for preventing nausea and vomiting induced by cisplatin-based chemotherapy in gynecological cancer: KCOG-G1301 phase II trial

Support Care Cancer. 2016 Feb;24(2):675-682. doi: 10.1007/s00520-015-2829-z. Epub 2015 Jul 1.

Abstract

Purpose: Olanzapine is effective in chemotherapy-induced nausea and vomiting (CINV). In patients receiving highly emetogenic chemotherapy (HEC), its efficacy was reported as rescue therapy for breakthrough emesis refractory to triplet therapy (palonosetron, aprepitant, and dexamethasone). However, its preventive effects with triplet therapy for CINV are unknown. This study aimed to investigate efficacy and safety of preventive use of olanzapine with triplet therapy for CINV of HEC.

Methods: This study is a prospective multicenter study conducted by Kansai Clinical Oncology Group. Forty chemo-naïve gynecological cancer patients receiving HEC with cisplatin (≥50 mg/m(2)) were enrolled. Oral olanzapine (5 mg) was administered with triplet therapy a day prior to cisplatin administration and on days 1-5. The primary endpoint was complete response (no vomiting and no rescue) rate for the overall phase (0-120 h post-chemotherapy). Secondary endpoints were complete response rate for acute phase (0-24 h post-chemotherapy) and delayed phase (24-120 h post-chemotherapy) and complete control (no vomiting, no rescue, and no significant nausea) rate and total control (no vomiting, no rescue, and no nausea) rate for each phase. These endpoints were evaluated during the first cycle of chemotherapy.

Results: Complete response rates for acute, delayed, and overall phases were 97.5, 95.0, and 92.5 %, respectively. Complete control rates were 92.5, 87.5, and 82.5 %, respectively. Total control rates were 87.5, 67.5, and 67.5 %, respectively. There were no grade 3 or 4 adverse events.

Conclusions: Preventive use of olanzapine combined with triplet therapy gives better results than those from previously reported studies of triplet therapy.

Keywords: Antiemetic therapy; Chemotherapy-induced nausea and vomiting; Cisplatin; Highly-emetogenic chemotherapy; Olanzapine.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antiemetics / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Aprepitant
  • Benzodiazepines / administration & dosage
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Dexamethasone / administration & dosage
  • Female
  • Genital Neoplasms, Female / drug therapy*
  • Humans
  • Isoquinolines / administration & dosage
  • Male
  • Middle Aged
  • Morpholines / administration & dosage
  • Nausea / chemically induced
  • Nausea / drug therapy
  • Nausea / prevention & control*
  • Olanzapine
  • Palonosetron
  • Prospective Studies
  • Quinuclidines / administration & dosage
  • Serotonin Antagonists / administration & dosage*
  • Vomiting / chemically induced
  • Vomiting / drug therapy
  • Vomiting / prevention & control*

Substances

  • Antiemetics
  • Isoquinolines
  • Morpholines
  • Quinuclidines
  • Serotonin Antagonists
  • Benzodiazepines
  • Aprepitant
  • Palonosetron
  • Dexamethasone
  • Olanzapine
  • Cisplatin