Mizukami, N., Yamauchi, M., Koike, K., Watanabe, A., Ichihara, K., Masumori, N., & Yamakage, M. (2014). Olanzapine for the prevention of chemotherapy-induced nausea and vomiting in patients receiving highly or moderately emetogenic chemotherapy: A randomized, double-blind, placebo-controlled study. Journal of Pain and Symptom Management, 47(3), 542–550.

DOI Link

Study Purpose

To determine whether adding olanzapine to current standard antiemetic therapy could reduce the frequency of chemotherapy-induced nausea and vomiting (CINV) and improve patients’ quality of life (QOL) during chemotherapy

Intervention Characteristics/Basic Study Process

Olanzapine 5 mg/day PO on days 0–5 versus a placebo in addition to 5-HT3RA (either granisetron, ondansetron, ramosetron, or palonosetron), dexamethasone (9.9 mg IV on day 1 followed by 6.6 mg IV on days 2–4), and NK1RA (aprepitant 125 mg orally on day 1 followed by 80 mg aprepitant orally on days 2 and 3 as a rescue drug for CINV). 10 mg of metoclopramide was administered intravenously as needed. Patients could use the rescue drug up to three times a day. The different 5-HT3 receptor antagonists used were administered as follows: granisetron 3–6 mg/day on days 1–3; ondansetron 4 mg/day on days 1–2; ramosetron 0.6 mg/day on days 1–3; and palonosetron 0.75 mg/day on day 1.

Sample Characteristics

  • N = 44 
  • MEAN AGE = 63 years (olanzapine group), 55 years (control group), non-significant difference p = .06
  • MALES: 50%, FEMALES: 50%
  • KEY DISEASE CHARACTERISTICS: Cancer patients receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC) with an Eastern Cooperative Oncology performance status of 0–2.
  • OTHER KEY SAMPLE CHARACTERISTICS: Patients had not experienced NVR in the 24 hours before the start of the trial, had not scheduled to receive concurrent abdominal radiation therapy, had no history of DM, were not receiving other antipsychotic agents, and were not hypersensitive to olanzapine.

Setting

  • SITE: Multi-site  
  • SETTING TYPE: Inpatient  
  • LOCATION: Sapporo, Hokkaido, Japan

Phase of Care and Clinical Applications

  • PHASE OF CARE: Active antitumor treatment

Study Design

Randomized, double-blind, placebo-controlled trial

Measurement Instruments/Methods

  • Primary endpoint: Total control (no vomiting, no use of rescue medications, and maximum nausea of < 5/100 mm)
  • Secondary endpoint: Functional Living Index–Emesis (FILE) questionnaire scores on days 0 and 6
  • Additional: QOL (FLIE), amount of diet intake during CTx, satisfaction, complete response (no vomiting, no use of rescue medication), complete control (complete response + nausea < 25 mm/100 mm), and Visual Analog Scale

Results

The olanzapine group achieved better total control (59% overall, 86% in the acute phase, and 64% in the delayed phase) than the control group (23% overall, 55% in the acute phase, and 23% in the delayed phase). The olanzapine group also achieved better complete protection and complete response except for acute phase complete response (p < .05). Furthermore, the olanzapine group experienced better QOL (p < .01), and the olanzapine group indicated that CINV did not affect their daily activities whereas 36% of the control group reported influence of CINV on daily life activities. There were significant differences between the VAS for nausea and satisfaction scores for additional medication. Most of the olanzapine group patients (91%) wished to receive same protocol for future chemotherapy. Dietary intake was better maintained by the olanzapine group with a significant difference on day 2 and days 4–6.

Conclusions

The addition of 5 mg/day of oral olanzapine to standard therapy can reduce the frequency of CINV and improve QOL for patients receiving highly or moderately emetogenic chemotherapy.

Limitations

  • Small sample (< 100)
  • Baseline sample/group differences of import
  • Risk of bias (sample characteristics)
  • Other limitations/explanation: Age of the olanzapine group was higher than the control (which could have influenced less development of CINV), and other risk factors of the CINV were not taken into consideration. MEC group also received NK1, which is not a standard antiemetic. Combination of palonosetron and olanzapine need to be investigated further, with stratification of emetogenicity of chemotherapy regimen, and the use of first and second generation 5-HT3RA between the two groups (as palonosetron 0.75mg was used in the study).

Nursing Implications

The addition of olanzapine to standard antiemetics, such as 5-HT3RA, steroids, and NK1RA, could achieve better control of CINV, especially for the delayed phase, with additional benefit in terms of QOL and less change in dietary intake. However, caution needs to be exercised in interpreting the result as the study allowed NK1 for the MEC, had age difference between the olanzapine and control group, and did not take risk factors of CINV into consideration, and the palonosetron dose of 0.75mg was higher than antiemetic recommendations.