Nakagaki, M., Barras, M., Curley, C., Butler, J.P., & Kennedy, G.A. (2017). A randomized trial of olanzapine versus palonosetron versus infused ondansetron for the treatment of breakthrough chemotherapy-induced nausea and vomiting in patients undergoing hematopoietic stem cell transplantation. Supportive Care in Cancer, 25, 607–613.

DOI Link

Study Purpose

To compare the effectiveness of infused ondansetron, olanzapine, and palonosetron for the treatment of breakthrough chemotherapy-induced nausea and vomiting (CINV) in recipients of hematopoietic stem cell transplantation (HSCT)

Intervention Characteristics/Basic Study Process

All patients received CINV prophylaxis of ondansetron 8 mg IV TID and aprepitant 165 mg PO (one dose). The aprepitant was given on the same day that the patients received high-dose cyclophosphamide or melphalan. All patients were able to take metoclopramide 10 mg PO or IV or lorazepam 1 mg sublingual for breakthrough CINV. Patients who required more than one dose of rescue antiemetics per day or had emesis or moderate/severe nausea (visual analog scale [VAS] ≥ 30 mm) were randomized into one of three treatment arms. 
  • Arm 1: Ondansetron 32 mg IV daily over 24 hours
  • Arm 2: Olanzapine 10 mg PO wafer daily plus ondansetron 8 mg IV TID
  • Arm 3: Palonosetron 0.25 mg IV (one dose) (did not receive ondansetron for three days)
Steroids could be administered for hypersensitivity to blood products or medications but could not be used as antiemetics. All other supportive medications were given per standard treatment protocol.

Sample Characteristics

  • N = 62   
  • AGE = 20–68
  • MALES: 62.9%, FEMALES: 37.1%
  • CURRENT TREATMENT: Chemotherapy, combination radiation and chemotherapy
  • KEY DISEASE CHARACTERISTICS: Recipients of allogeneic or autologous HSCT

Setting

  • SITE: Not stated/unknown   
  • SETTING TYPE: Not specified    
  • LOCATION: Australia

Phase of Care and Clinical Applications

  • PHASE OF CARE: Active antitumor treatment
  • APPLICATIONS: Elder care

Study Design

Randomized, open-label, prospective study

Measurement Instruments/Methods

  • Patients documented the number of emesis events and severity of nausea, which was measured with a 100 mm VAS ranging from 0 (no nausea) to 100 (worst possible nausea).
  • After patients were randomized into a treatment arm, data were collected at 24 hours and 48 hours postinitiation of treatment. Patients were asked to score the overall intensity and frequency of nausea for the previous 24 hours. 
  • Rescue antiemetic doses were obtained from the medication record.

Results

Primary end points were defined as no emesis, no use of rescue antiemetics, and reduction in nausea severity of 50% or more compared to nausea severity at the time of randomization. The secondary end point was defined as a nausea score reduction of 50% or more compared to nausea severity at the time of randomization. Six percent of patients receiving ondansetron, 45% of patients receiving olanzapine, and 18% of patients receiving palonosetron achieved the primary end point at 24 hours. Six percent of patients receiving ondansetron, 64% percent of patients receiving olanzapine, and 18% of patients receiving palonosetron achieved the primary end point at 48 hours. Olanzapine was significantly more effective than ondansetron at 24 and 48 hours (p = 0.01 and 0.0002). Olanzapine was significantly more effective than palonosetron at 48 hours (p = 0.005). For the secondary end point, olanzapine was significantly more effective than ondansetron at 24 and 48 hours (p = 0.0009 and p = 0.048) but was not significantly different than palonosetron at either time point. Palonosetron was significantly more effective than ondansetron at 24 hours (p =  0.008).

Conclusions

Olanzapine is an effective treatment for breakthrough CINV after an allogeneic or autologous hematopoietic stem cell transplantation when used with standard prophylaxis of ondansetron and aprepitant.

Limitations

  • Small sample (< 100)
  • Risk of bias (no blinding)

 

Nursing Implications

For the treatment of breakthrough CINV in recipients of HSCT receiving prophylactic ondansetron and aprepitant, olanzapine is superior to palonosteron and ondansetron. This is an indication to include this as a part of patients' antiemetic regimens.