Recommended for Practice

Olanzapine

for Chemotherapy-Induced Nausea and Vomiting—Adult

Olanzapine is an antipsychotic used in the treatment of schizophrenia and bipolar disorder. It also has been evaluated as an adjunctive medication for the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) in patients with cancer.

Systematic Review/Meta-Analysis

Chiu, L., Chow, R., Popovic, M., Navari, R.M., Shumway, N.M., Chiu, N., . . . DeAngelis, C. (2016). Efficacy of olanzapine for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting (CINV): A systematic review and meta-analysis. Supportive Care in Cancer, 24, 2381–2392. 

Purpose

STUDY PURPOSE: To evaluate the effectiveness of olanzapine compared to other antiemetic regimens for preventative and breakthrough chemotherapy-induced nausea and vomiting (CINV). A secondary objective is to evaluate the effectiveness of 5 mg compared to 10 mg olanzapine for the prevention of CINV.

TYPE OF STUDY: Meta-analysis and systematic review

Search Strategy

DATABASES USED: Ovid MEDLINE, EMBASE, EMBASE Classic, and Cochrane Central Registrar of Controlled Trials
 
INCLUSION CRITERIA: Randomized controlled trials that evaluated olanzapine with other antiemetics for the prevention or treatment of either breakthrough emesis or nausea between 1946–2015
 
EXCLUSION CRITERIA: None stated

Literature Evaluated

TOTAL REFERENCES RETRIEVED: Not stated
 
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: No evaluation method stated

Sample Characteristics

  • FINAL NUMBER STUDIES INCLUDED = 13 total studies, 10 for prevention and 3 for breakthrough CINV
  • TOTAL PATIENTS INCLUDED IN REVIEW = 1,082 patients for prevention and 308 patients for breakthrough
  • SAMPLE RANGE ACROSS STUDIES: Prevention studies: 19–241 patients; breakthrough studies: 106–109 patients
  • KEY SAMPLE CHARACTERISTICS: Prevention studies: Six studies included patients with HEC, four with both HEC and MEC, and no studies with only MEC. Breakthrough studies: Two studies included patients with MEC, and one study included HEC.

Phase of Care and Clinical Applications

PHASE OF CARE: Active antitumor treatment
 
APPLICATIONS: Elder care

Results

Efficacy of Acute Phase: Olanzapine was statistically superior to non-olanzapine regimens for emesis (RR = 1.10, 95% CI [1.03, 1.17]) but not nausea. The 10 mg olanzapine was statistically superior to a non-olanzapine regimen for emesis and nausea.

Efficacy of Delayed Phase: Olanzapine was statistically superior to standard antiemetic regimens for emesis (RR = 1.31, 95% CI [1.14, 1.52]) and for nausea (RR = 1.50, 95% CI [1.15, 1.97]). The 10 mg olanzapine was statistically superior to a non-olanzapine regimen for emesis (RR = 1.31, 95% CI [1.11, 1.54]) and nausea (RR = 1.50, 95% CI [1.15, 1.97]).

Efficacy Overall: Olanzapine was statistically superior to standard anti-emetic regimens for emesis (RR = 1.41, 95% CI [1.18, 1.68]) and for nausea (RR 1.53, 95% CI [1.18, 1.97]). Olanzapine 5 mg and 10 mg were both statistically superior for emesis, and 10 mg strength was superior for nausea. No studies were available for nausea with 5 mg.

Efficacy of Breakthrough: Only emesis (not nausea) was available for analysis, and olanzapine showed superiority (RR = 2.09, 95% CI [1.63, 2.68]) to non-olanzapine regimens.

Conclusions

Olanzapine is effective in treating emesis at all time points and is effective in treating nausea in the delayed phase. More studies are needed to determine the most effective dosing.

Limitations

  • Limited number of studies included
  • Low sample sizes
  • A secondary objective was to evaluate the effectiveness of 5 mg compared to 10 mg, but no results were found to answer this objective (5 mg and 10 mg were compared only to non-olanzapine regimens).

Nursing Implications

Olanzapine should be used as an adjunct medication for the treatment of acute chemotherapy related vomiting, breakthrough vomiting, and delayed CINV.

Print

Chow, R., Chiu, L., Navari, R., Passik, S., Chiu, N., Popovic, M., . . . DeAngelis, C. (2015). Efficacy and safety of olanzapine for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) as reported in phase I and II studies: A systematic review. Supportive Care in Cancer, 24, 1001–1008. 

Purpose

STUDY PURPOSE: To summarize evidence from phase I and II trials in which olanzapine was used for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV)

TYPE OF STUDY: Systematic review

Search Strategy

DATABASES USED: MEDLINE, EMBASE, and the Cochrane Collaboration
 
KEYWORDS: Nausea and vomiting, vomiting and chemotherapy, nausea and chemotherapy, and olanzapine and CINV
 
INCLUSION CRITERIA: Phase I and II trials reporting on use of olanzapine for CINV reporting on CINV outcomes; single-arm uncontrolled trials 
 
EXCLUSION CRITERIA: Not specified

Literature Evaluated

TOTAL REFERENCES RETRIEVED: 356
 
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: No quality evaluation was described

Sample Characteristics

  • FINAL NUMBER STUDIES INCLUDED = 7 
  • TOTAL PATIENTS INCLUDED IN REVIEW = 201
  • SAMPLE RANGE ACROSS STUDIES: 3–40 patients
  • KEY SAMPLE CHARACTERISTICS: Multiple tumor types across studies; highly and moderately emetogenic chemotherapy regimens

Phase of Care and Clinical Applications

PHASE OF CARE: Active antitumor treatment

Results

The rate of complete control (no emesis, no rescue medication, and no significant nausea) was only identified in one study. Complete response rates were reported in three studies, and they ranged from 75%–100% in the acute phase and 72%–92.5% in the overall phase. In four trials, olanzapine was used as an adjunct with other antiemetics. One study was a retrospective chart review.

Conclusions

The findings of this study suggest that olanzapine can be beneficial in preventing CINV.

Limitations

  • The sample sizes of the studies were small.
  • No information was provided regarding the use of any other antiemetics. 
  • How a study using a retrospective chart review constitutes as a phase I or II study for inclusion was unclear.

Nursing Implications

The potential role of olanzapine in the prevention and management of CINV is unclear. This review provides limited evidence of the effects of olanzapine for CINV. Future studies need to compare olanzapine as an adjuvant to recommended antiemetics or olanzapine as a single agent compared to regimens with clear efficacy for the prevention of CINV.

Print

Wang, X.F., Feng, Y., Chen, Y., Gao, B.L., & Han, B.H. (2014). A meta-analysis of olanzapine for the prevention of chemotherapy-induced nausea and vomiting. Scientific Reports, 4, 4813. 

Purpose

STUDY PURPOSE: To determine the effectiveness of olanzapine in the prevention of chemotherapy-induced nausea and vomiting (CINV) after moderately to highly emetogenic chemotherapy
 
TYPE OF STUDY: Meta-analysis and systematic review

Search Strategy

DATABASES USED: MEDLINE, PubMed, The China National Knowledge Infrastructure, Wanfang Data, and the Weipu Periodical Database  
 
KEYWORDS: Olanzapine, CINV, chemotherapy-induced nausea and vomiting, nausea, and vomiting 
 
INCLUSION CRITERIA: Randomized controlled trials; olanzapine use in CINV; blinded studies; published studies; cost-effective studies; published in English or Chinese; date range 1990 through October 2013
 
EXCLUSION CRITERIA: Studies that were not cost-effective; repetition with former research; retrospective studies; use in patients with incomplete bowel obstruction; and use for breakthrough emesis

Literature Evaluated

TOTAL REFERENCES RETRIEVED: Thirteen relevant articles
 
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: A flow diagram of the search strategy was developed by the investigators and used to select relevant articles. Both English and Chinese literature were searched.

Sample Characteristics

  • FINAL NUMBER STUDIES INCLUDED = 6 
  • TOTAL PATIENTS INCLUDED IN REVIEW = 726
  • KEY SAMPLE CHARACTERISTICS: All studies defined complete response as no vomiting or use of rescue medications. Five studies compared standard antiemetic regimens without olanzapine to standard antiemetic regimens with olanzapine.

Phase of Care and Clinical Applications

PHASE OF CARE: Active antitumor treatment
 
APPLICATIONS: Elder care, palliative care

Results

Five out of six studies demonstrated an increase in complete response in patients receiving standard antiemetic regimens plus olanzapine on day 1 of chemotherapy (odds ratio [OR] = 1.95, 95%; confidence interval [CI] = 1.17–3.23; p = 0.01). Five out of six studies showed a cumulative delay in vomiting (OR = 2.65, 95%; CI = 1.36–5.15; p = 0.004). Overall complete response relative risk was improved (4.07, 95%; CI = 1.59–10.43). Also note the following: delayed-phase antinausea effects in olanzapine-containing antiemetic regimens (OR = 2.79, 95%; CI = 1.76–4.43; p = 0.0001); antinausea effects in the overall phase (OR = 3.40, 95% CI = 2.32–5.00; p = 0.00001); and no superiority in the acute phase (RR = 1.34, 95%; CI = 0.77–2.34; p = 0.30).

Conclusions

Complete response is more likely in patients who received antiemetic regimens containing olanzapine compared to patients who did not receive olanzapine. Olanzapine is more effective in delayed CINV than acute.

Limitations

  • Small sample
  • Differences in what drugs were included in standard antiemetic regimens in each study
  • One study used aprepitant in the standard antiemetic regimen.

Nursing Implications

Olanzapine may add CINV control when added to a standard antiemetic regimen during the delayed phase.

Print

Yoodee, J., Permsuwan, U., & Nimworapan, M. (2017). Efficacy and safety of olanzapine for the prevention of chemotherapy-induced nausea and vomiting: A systematic review and meta-analysis. Critical Reviews in Oncology/Hematology, 112, 113–125.

Purpose

STUDY PURPOSE: The primary aim of this systematic review was to compare the efficacy and safety of olanzapine with standard antiemetics.

TYPE OF STUDY: Systematic review/meta-analysis

Search Strategy

DATABASES USED: MEDLINE, EMBASE, SCOPUS, Cochran Central Register of Controlled Trials

YEARS INCLUDED: Inception to July 15, 2016

INCLUSION CRITERIA: The studies of interest were those that reported either olanzapine as add-on treatment (dexamethasone plus 5-HT3 antagonist, with or without NK1 antagonist) or olanzapine monotherapy compared to standard treatment. 

EXCLUSION CRITERIA: Duplicate data and non-English language studies.

Literature Evaluated

TOTAL REFERENCES RETRIEVED: 573

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Two independent reviewers

Sample Characteristics

FINAL NUMBER STUDIES INCLUDED: 16 studies however, only 9 were pooled for statistical analysis because 1 was an observational study, and 6 clinical trials did not have a comparison group. 

TOTAL PATIENTS INCLUDED IN REVIEW 1,308 (in the 9 studies included in analysis) 

SAMPLE RANGE ACROSS STUDIES: 17-380

KEY SAMPLE CHARACTERISTICS: Multiple tumor types, focused on patients receiving olanzapine.

Phase of Care and Clinical Applications

PHASE OF CARE: Active anti-tumor treatment

Results

The results of the combined studies included in the meta-analysis showed that CR (defined as no emesis and no rescue drugs) was achieved more frequently for delayed CINV (RR = 1.77, 95% CI [1.07, 1.49]) and overall CINV (RR = 1.32; 95% CI [1.08, 1.62]). Olanzapine was not superior to traditional antiemetic therapy for acute CINV. The most frequently occurring adverse events were drowsiness and constipation.

Limitations

  • Limited number of studies included
  • High heterogeneity
  • Multiple measures used to determine the presence of nausea and vomiting.

Nursing Implications

Nurses caring for patients with delayed CINV can consider the use of olanzapine, but also must recognize the common occurring drowsiness and constipation with the use of the medication.

Print

Research Evidence Summaries

Abe, M., Hirashima, Y., Kasamatsu, Y., Kado, N., Komeda, S., Kuji, S., . . . Ito, K. (2015). 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. Supportive Care in Cancer, 24, 675–682. 

Study Purpose

To investigate the effects of olanzapine as an adjunct to triplet antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy

Intervention Characteristics/Basic Study Process

All patients in the trial were receiving triplet therapy in accordance with Japanese guidelines and 5 mg olanzapine one day prior to cisplatin administration then once daily on days 1–5 at bedtime. Metoclopramide was used as rescue therapy for breakthrough emesis. Patients were hospitalized during treatment.

Sample Characteristics

  • N = 40
  • MEDIAN AGE = 57 years (range 25–76 years)
  • FEMALES: 100%
  • KEY DISEASE CHARACTERISTICS: All had cervical, endometrial, or vulval cancer at varied stages. 50% experienced emesis during pregnancy, and 32.5% had a history of motion sickness. Most received cisplatin at a dose of 50mg/m2 and 95% had multiagent regimens.

Setting

  • SITE: Multi-site  
  • SETTING TYPE: Inpatient    
  • LOCATION: Japan

Phase of Care and Clinical Applications

  • PHASE OF CARE: Active antitumor treatment

Study Design

Prospective trial

Measurement Instruments/Methods

  • Patient diary for daily self-reported symptoms
  • Eleven-point Numeric Rating Scale (NRS) for nausea
  • Complete response defined as no vomiting, no rescue therapy and no significant nausea
  • Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Results

There were no grade 3 or 4 adverse events. In the overall phase (acute and delayed phases), the complete response rate was 92.5% with 97.5% in the acute phase and 95% in the delayed phase. The rate for no nausea was 87.5% in the acute phase and 67.5% in the delayed phase. The authors provided a comparison of this study's results with those of a collaborative group trial using triplet therapy. This comparison showed that the addition of olanzapine was associated with better response rates across all phases and higher rates of nausea control. The adverse effects reported were low-grade and included constipation, dry mouth, and dizziness.

Conclusions

The addition of olanzapine to triplet antiemetic therapy in patients receiving highly emetogenic chemotherapy was associated with high rates of complete CINV control across all phases and relatively low rates of nausea during the acute phase.

Limitations

  • Small sample (< 100)
  • Risk of bias (no control group)
  • Risk of bias (no blinding)
  • Risk of bias (no random assignment)
  • Other limitations/explanation: The results were complete control and no significant nausea, but these were not defined and the level of no significant nausea was not clear. The way in which the numeric scale data were used was not clear (i.e., was this the average, worst, or least scores recorded by the patient).

Nursing Implications

Triplet drug therapy to prevent CINV is recommended and is effective with highly emetogenic chemotherapy. However, even with this approach, the control and prevention of nausea is challenging. The findings of this study suggest the addition of olanzapine to triplet therapy may improve nausea control and overall CINV prevention with no severe adverse effects. This study has several limitations, but provides promising results. Additional, well-designed research testing the impact of olanzapine for CINV prevention is warranted.

Print

Babu, G., Saldanha, S.C., Kuntegowdanahalli Chinnagiriyappa, L., Jacob, L.A., Mallekavu, S.B., Dasappa, L., . . . Arroju, V. (2016). The efficacy, safety, and cost benefit of olanzapine versus aprepitant in highly emetogenic chemotherapy: A pilot study from South India. Chemotherapy Research and Practice, 2016, 3439707. 

Study Purpose

To compare the efficacy, safety, and cost of olanzapine-based triplet antiemetics compared to the use of aprepitant as part of antiemetics in chemotherapy-naïve patients receiving highly emetogenic chemotherapy

Intervention Characteristics/Basic Study Process

The olanzapine group received 10 mg olanzapine orally (PO), 0.25 mg palonosetron intravenously (IV), and 20 mg dexamethasone IV on day 1; and then 5 mg olanzapine PO and 4 mg dexamethasone PO on days 2–4. The aprepitant group was given 125 mg aprepitant PO, 0.25 mg palonosetron IV, and 12 mg dexamethasone IV on day 1; 80 mg aprepitant PO on days 2 and 3; and 4 mg dexamethasone PO on days 2–4. Patients were asked to record the intensity of nausea, the use of rescue medication, and vomiting daily in a diary. Patients were contacted daily for reminders to record symptoms.

Sample Characteristics

  • N = 100   
  • MEAN AGE = 43.6 years
  • MALES: 30%, FEMALES: 70%
  • CURRENT TREATMENT: Chemotherapy
  • KEY DISEASE CHARACTERISTICS: Patients had various tumor types, and the majority were breast cancer.
  • OTHER KEY SAMPLE CHARACTERISTICS: The study included patients receiving various types of highly emetogenic chemotherapy, and all received six cycles.

Setting

  • SITE: Single site   
  • SETTING TYPE: Outpatient    
  • LOCATION: India

Phase of Care and Clinical Applications

PHASE OF CARE: Active antitumor treatment

Study Design

  • Prospective, two-group, non-randomized trial

Measurement Instruments/Methods

  • Visual analog scale (VAS) for nausea intensity 
  • CTC
  • Complete response defined as no emesis and no rescue medication
  • Complete response recorded for acute, delayed, and overall periods

Results

No significant differences existed between groups in complete response rates or nausea severity. No grade 3 or 4 toxicities existed. Adverse events associated with olanzapine were sedation and dizziness in less than 10% of patients.

Conclusions

Olanzapine-based triplet antiemetic therapy was as effective as aprepitant-based triplet antiemetics in this study.

Limitations

  • Risk of bias (no blinding)
  • Risk of bias (no random assignment)
  • No information provided on timing of measurements analyzed or trends over time
  • No information on rescue medications used

Nursing Implications

Findings suggest that the use of olanzapine in substitution for an NK1 in a triplet antiemetic regimen was effective. The study is limited by its lack of random assignment to study groups, but the groups were well matched on most demographic and other treatment variables. Olanzapine is much less expensive than an NK1 and may be a good alternative for patients who have limited financial resources or insurance coverage for antiemetics.

Print

Chiu, L., Chiu, N., Chow, R., Zhang, L., Pasetka, M., Stinson, J., . . . DeAngelis, C. (2016). Olanzapine for the prophylaxis and rescue of chemotherapy induced nausea and vomiting (CINV): A retrospective study. Annals of Palliative Medicine, 5, 172–178.

Study Purpose

Evaluate the safety and efficacy of olanzapine for prevention and rescue of CINV

Intervention Characteristics/Basic Study Process

Medical records of adult patients who received one or more doses of olanzapine for prophylaxis of CINV or treatment of breakthrough CINV were reviewed. Routinely patients are phoned by a pharmacist or research assistant 72 hours after each chemotherapy cycle and an assessment of CINV is documented in the electronic record. Patients were on various chemotherapy and antiemetic regimens.

Sample Characteristics

  • N: 170   
  • AGE: Median = 51 years (range = 20-85)
  • MALES: 16.5%  
  • FEMALES: 83.5%
  • CURRENT TREATMENT: Chemotherapy
  • KEY DISEASE CHARACTERISTICS: Various tumor types–breast was most common (57%)

Setting

  • SITE: Single site   
  • SETTING TYPE: Outpatient    
  • LOCATION: Canada

Study Design

Retrospective descriptive

Results

Olanzapine was used for breakthrough in 154 patients over 193 treatment cycles. 88.1% of patients reported that it improved nausea, and 21.8% reported it improved vomiting. Twenty patients had been given olanzapine for prophylaxis. Among these 100% reported it improved nausea, and 35% said it improved vomiting. Analysis showed that olanzapine effects were not related to cycle, emetogenicity of the chemotherapy, or antiemetic regimen used. Side effects observed were sedation with continuation of olanzapine (29.5%).

Conclusions

Olanzapine was shown to have been effective as a rescue medication for CINV and may be effective for CINV prophylaxis.

Limitations

  • Baseline sample/group differences of import         
  • Risk of bias (no control group)
  • Risk of bias (no blinding)
  • Risk of bias (no random assignment)
  • Measurement/methods not well described
  • Measurement validity/reliability questionable
  • Other limitations/explanation: No subgroup analysis based on emetogenicity of chemotherapy and antiemetic regimen–these factors could confound results seen. No standard approach to measurement or reporting of CINV symptoms.

Nursing Implications

Olanzapine can be effective as a rescue medication for CINV and as part of a CINV prophylaxis regimen.

Print

Liu, J., Tan, L., Zhang, H., Li, H., Liu, X., Yan, Z., . . . Zhang, D. (2015). QoL evaluation of olanzapine for chemotherapy-induced nausea and vomiting comparing with 5-HT3 receptor antagonist. European Journal of Cancer Care, 24, 436–443. 

Study Purpose

To evaluate the effect of olanzapine on quality of life (QOL) during chemotherapy compared with a 5HT3 receptor antagonist

Intervention Characteristics/Basic Study Process

Patients receiving multiple different chemotherapy regimens were randomized to one of two groups. Group one received olanzapine 10 mg PO, azasetron 10mg IV, and dexamethasone 10 mg IV, followed by olanzapine 10 mg PO on days 2-5. The control group received azasetron 10 mg IV and dexamethasone 10 mg IV, followed by dexamethasone 10 mg IV on days 2-5. Use of breakthrough antiemetics was permitted based on clinical circumstances. It is not reported whether patients received one cycle only. Patients were not all chemotherapy naive, but this was not controlled in the sample description.

Sample Characteristics

  • N = 229  
  • AGE = 18-74 years
  • MALES: 65%-72%, FEMALES: 43%-49%
  • KEY DISEASE CHARACTERISTICS: lung, breast, colorectal, lymphoma, ovarian, stomach, esophageal, teratoma, thymus, oropharyngeal, cervical, gingival, melanoma, and glioblastoma. All patients were receiving moderately or highly emetogenic chemotherapy.
  • OTHER KEY SAMPLE CHARACTERISTICS: normal CBC, LFTs, metabolic profile, normal cardiac function, EKG, performance status of 2 or better, no nausea preceding 24 hours. Multiple exclusion criteria.

Setting

  • SITE: Single site    
  • SETTING TYPE: Not specified    
  • LOCATION: Harbin Medical University, China

Phase of Care and Clinical Applications

  • PHASE OF CARE: Active antitumor treatment

Study Design

  • Randomized trial using random digits

Measurement Instruments/Methods

  • EORTC-QLQ C30 was measured on day 0 and 6. CINV was measured with Common Toxicity Criteria.

Results

There was no significant difference in acute CINV, but delayed CINV showed complete response rates of 76.85% in the olanzapine group and 46.2% in the 5HT3 group (p < 0.05). CINV was also better controlled in five days post chemotherapy, with 85.95% in the olanzapine arm and 67.59% in the control arm. Not all patients completed QOL. Global health status, emotional functioning, social functioning, fatigue, CINV, and insomnia were improved in the olanzapine group. Pain and dyspnea improved in both groups.

Conclusions

CINV influences QOL for patients undergoing chemotherapy. Although olanzapine did not change CINV in the acute phase, it showed significance in the delayed CINV group. This demonstrated improvements in global health status, fatigue, and insomnia. 5HT3 antagonists were effective against acute CINV but not effective in delayed CINV.

Limitations

  • Risk of bias (no blinding)
  • Other limitations/explanation: The authors did not identify any limitations. All data comparisons were not identified. Description of prior treatments for patients were not listed. No subgroup analysis was completed between those receiving MEC and HEC regimens. No information was provided regarding use of other antiemetics as allowed in the study protocol

Nursing Implications

Olanazapine offers another option for treatment of CINV. Other symptoms may also be controlled with this medication, such as insomnia, appetite loss, fatigue, and global health status. Nurses can consider this when standard medications are ineffective.

Print

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.

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.

Print

Mukhopadhyay, S., Kwatra, G., Pamela, A.K., & Badyal, D. (2017). Role of olanzapine in chemotherapy-induced nausea and vomiting on platinum-based chemotherapy patients: A randomized controlled study. Supportive Care in Cancer, 25, 145–154. 

Study Purpose

To evaluate the efficacy of olanzapine in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving platinum-based chemotherapy and prophylactic palonosetron and dexamethasone

Intervention Characteristics/Basic Study Process

The authors defined moderately emetogenic chemotherapy (MEC) as cisplatin less than 50 mg/m2, carboplatin, and oxaliplatin. Highly emetogenic chemotherapy (HEC) was defined as cisplatin 50 mg/m2​ or greater. On day 1 of MEC or HEC, all patients received palonosetron 0.25 mg IV and dexamethasone 30–60 minutes prior to chemotherapy administration. Patients receiving MEC received 8 mg of dexamethasone IV, and patients receiving HEC received 16 mg of dexamethasone IV. Patients receiving MEC received 8 mg dexamethasone PO daily on days 2 and 3, and patients receiving HEC received 8 mg dexamethasone PO BID on days 2–4. Patients in the test group received the above regimen and olanzapine 10 mg PO on day 1 prior to chemothearpy and then on days 2–5. For all patients, metoclopramide 10–20 mg PO or IV was allowed for rescue medication per the treating clinicians.

Sample Characteristics

  • N = 100   
  • MEAN AGE = Control group: 55.04 years (SD = 1.5); test group: 53.66 years (SD = 1.55)
  • MALES: 58%, FEMALES: 42%
  • CURRENT TREATMENT: Chemotherapy
  • KEY DISEASE CHARACTERISTICS: Head and neck cancer, cervical cancer, esophageal cancer, ovarian cancer

Setting

  • SITE: Single site   
  • SETTING TYPE: Not specified
  • LOCATION: Hospital in northwest India

Phase of Care and Clinical Applications

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

Study Design

This was a randomized, controlled, assessor-blind study.

Measurement Instruments/Methods

Patients recorded the frequency and time of emetic episodes and the frequency and time of rescue antiemetics for the first five days. Patients also used the Multinational Association for Supportive Care in Cancer (MASCC) Antiemesis Tool (MAT) to record the control of nausea and vomiting and intensity of symptoms from days 1–5. Patients also recorded any adverse effects on days 1, 3, and 8–10 and as needed, as well as the duration and severity of the adverse effect. A trained nurse assessed all patients between day 8–10. At this time, the patients' overall quality of life was assessed using the European Organization for Research and Treatment of Cancer Core Quality of Life (EORTC QLQ-C30), version 3, questionnaire.

Results

Complete response was defined as no emesis and no rescue medications on days 1–5. Complete control was defined as no emetic episodes, no rescue medications, and no moderate or severe nausea on days 1–5. Nausea in the delayed phase was significantly less in the test group patients (p < 0.0001). Complete response was significantly higher in the test groups for delayed emesis and overall (p < 0.0001 and p < 0.0001). Complete control was significantly higher in the test groups for delayed emesis and overall (p < 0.0001 and p < 0.0001). Failure was defined as at least one antiemetic episode or use of rescue antiemetics on days 1–5. Failure was higher in the control group for delayed emesis and overall (p = 0.007 and p = 0.0038).

Conclusions

For patients receiving platinum-based chemotherapy, olanzapine is an effective addition for the prevention of CINV. The only side effect listed is more sedation.

Limitations

Findings not generalizable

Nursing Implications

Olanazpine is effective for the prevention of CINV in this sample with few adverse effects. It may not be generalizable, but more studies are supporting its use.

Print

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.

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.

Print

Navari, R.M., Nagy, C.K., Le-Rademacher, J., & Loprinzi, C.L. (2016). Olanzapine versus fosaprepitant for the prevention of concurrent chemotherapy radiotherapy-induced nausea and vomiting. The Journal of Community and Supportive Oncology, 14, 141–147. 

Study Purpose

To compare the effectiveness of an olanzapine-based triple-drug antiemetic regimen with a fosaprepitant-based triple-drug regimen

Intervention Characteristics/Basic Study Process

Patients were randomized to either olanzapine, palonosetron, and dexamethasone (OPD) or fosaprepitant, palonosetron, and dexamethasone (FPD) before the first course of chemotherapy. The OPD regimen was palonosetron 0.25 mg and dexamethasone 20 mg IV prior to chemotherapy and 10 mg PO olanzapine on days 1–4. The FPD regimen was 12 mg dexamethasone, 0.25 mg palonosetron and 150 mg fosaprepitant IV prior to chemotherapy, followed by oral dexamethasone 4 mg twice daily on days 2–3. Patients were allowed to take rescue medication. All patients received a placebo to ensure that the medication provided looked identical to the patient. Daily episodes of vomiting, symptom intensity, and use of rescue therapy were recorded by the patient in a diary for five days.

Sample Characteristics

  • N = 101   
  • MEDIAN AGE = 62 years
  • AGE RANGE = 52–76 years
  • MALES: 78.2%, FEMALES: 21.8%
  • CURRENT TREATMENT: Combination radiation and chemotherapy
  • KEY DISEASE CHARACTERISTICS: Patients with locally advanced head and neck or esophageal cancer receiving HEC and daily radiotherapy

Setting

  • SITE: Multi-site   
  • SETTING TYPE: Outpatient    
  • LOCATION: United States

Phase of Care and Clinical Applications

PHASE OF CARE: Active antitumor treatment

Study Design

  • Single-blind, placebo-controlled, randomized trial

Measurement Instruments/Methods

  • MD Anderson Symptom Inventory (MDASI) mean of daily MDASI scores was used in analysis
  • Visual analog scale (VAS) for nausea severity
  • Complete response defined as no emesis and no use of rescue medication

Results

No difference existed between groups in complete response for the acute period. For the delayed and overall periods, those on the olanzapine regimen showed a CR rate of 76% compared to 74% in the comparison group. Twelve percent of the OPD group required rescue during the acute phase, and 12% required rescue medication during the delayed period. In the FPD group, 10% required rescue during the delayed phase, and 26% required rescue medication in the acute period. The percentage of patients with no nausea was higher in the OPD group in all phases (p < 0.01). Patients on olanzapine had more drowsiness that was resolved by day 3–4.

Conclusions

Findings suggest that both the standard triple-drug antiemetic regimen and the olanzapine-based regimen were effective in controlling vomiting. As a greater proportion of those receiving olanzapine had no nausea, the olanzapine regimen may provide greater nausea control.

Nursing Implications

This study showed that both antiemetic regimens were similar in terms of control of emesis and need for rescue medications, and that nausea was better controlled with olanzapine. Nausea has been more difficult to control with currently used antiemetic regimens. These results suggest that olanzapine-based regimens may provide better nausea control. Olanzapine is also generally much less expensive than NK1s, providing a good treatment alternative at a lower cost.

Print

Navari, R.M., Qin, R., Ruddy, K.J., Liu, H., Powell, S.F., Bajaj, M., . . . Loprinzi, C.L. (2016). Olanzapine for the prevention of chemotherapy-induced nausea and vomiting. New England Journal of Medicine, 375, 134–142. 

Study Purpose

To evaluate olanzapine for chemotherapy-induced nausea and vomiting (CINV) prophylaxis in patients receiving highly emetogenic chemotherapy (HEC) and to evaluate potential toxic effects

Intervention Characteristics/Basic Study Process

Patients were stratified according to gender, chemotherapy regimen, and the specific 5HT3 used. All patients were on triplet antiemetic regimens. In addition, patients received 10 mg oral olanzapine daily or placebo on days 1–4. Patients were to complete daily records of vomiting, nausea severity, and use of rescue therapy.

Sample Characteristics

  • N = 369   
  • MEDIAN AGE = 57 years
  • MALES: 27.6%, FEMALES: 72.4%
  • KEY DISEASE CHARACTERISTICS: Most had breast cancer, and 12% had lung cancer.
  • OTHER KEY SAMPLE CHARACTERISTICS: All patients were chemotherapy-naïve, 35% were on cisplatin-based regimens, and 64% were on anthracycline and cyclophosphamide.

Setting

  • SITE: Multi-site   
  • SETTING TYPE: Outpatient    
  • LOCATION: United States

Phase of Care and Clinical Applications

PHASE OF CARE: Active antitumor treatment

Study Design

  • Double-blind, placebo-controlled, randomized controlled trial

Measurement Instruments/Methods

  • Visual analog scale (VAS) for nausea severity
  • Complete response rated in acute and delayed phase
  • Use of rescue medications

Results

During the acute phase, 73.8% on olanzapine had no nausea compared to 45.3% on placebo (p < 0.001), and in the delayed phase, 42.4% on olanzapine and 25.4% on placebo had no nausea (p = 0.001). The complete response rate with olanzapine in the acute phase was 85.7% compared to 64.6% with placebo (p < 0.001). In the delayed phase, complete response was 66.9% with olanzapine and 53.4% with placebo (p = 0.007). Those on olanzapine had significantly more sedation on day 2, which then resolved in the following days.

Conclusions

The addition of olanzapine as an adjunct to standard triplet antiemetic regimens for patients receiving HEC was more effective than placebo for CINV control.

Nursing Implications

Findings suggest that the use of olanzapine as an adjunct to usual triplet therapy for CINV control was effective in improving complete response rates and nausea, although complete response rates reported here are not higher than those often reported with standard triplet therapy. Nausea was also improved with olanzapine, although almost half the participants still had nausea in the delayed phase. Clinicians can consider the addition of olanzapine to standard antiemetic regimens for individuals at high risk for CINV or those who may have had inadequate CINV control in previous chemotherapy cycles. Ongoing research is still needed to achieve greater nausea control.

Print

Sato, J., Kashiwaba, M., Komatsu, H., Ishida, K., Nihei, S., & Kudo, K. (2016). Effect of olanzapine for breast cancer patients resistant to triplet antiemetic therapy with nausea due to anthracycline-containing adjuvant chemotherapy. Japanese Journal of Clinical Oncology, 46, 415–420. 

Study Purpose

To determine the effectiveness and safety of adding olanzapine to triple antiemetic therapy with aprepitant, palonosetron, and dexamethasone as highly emetic anthracycline-containing adjuvant chemotherapy for patients with primary breast cancer

Intervention Characteristics/Basic Study Process

Forty-five patients with breast cancer who experienced greater than grade 1 nausea or any vomiting after the first cycle of chemotherapy using both epirubicin and cyclophosphamide were included. Low-dose olanzapine (2.5 mg per day) was administered orally from the first day of chemotherapy for four days, and the number of episodes of vomiting, scale of nausea, dietary intake, and somnolence were compared with the symptoms after the first cycle.

Sample Characteristics

  • N = 45   
  • MEAN AGE = 49.7 (SD = 13 years)
  • FEMALES: 100%
  • CURRENT TREATMENT: Chemotherapy
  • KEY DISEASE CHARACTERISTICS: Patients with breast cancer receiving 5-flourouracil, epirubicin, and cyclophosfamide (FEC) or epirubicin and cyclophosphamide (EC) therapy in an adjuvant or neoadjuvant setting

Setting

  • SITE: Single site   
  • SETTING TYPE: Inpatient    
  • LOCATION: Iwate Medical University Hospital

Phase of Care and Clinical Applications

  • PHASE OF CARE: Active antitumor treatment

Study Design

  • Nonrandomized, prospective, phase-II trial without placebo control

Measurement Instruments/Methods

  • Common Terminology Criteria for Adverse Events
  • Clopper-Pearson method
  • Excel statistics
  • Cochran-Armitage test
  • Paired t-test or Dunnett t-test

Results

The nausea was significantly improved by adding olanzapine (p < 0.05). The mean nausea scale and dietary intake were improved by adding olanzapine.

Conclusions

Adding low-dose olanzapine for patients with insufficient nausea relief with triplet antiemetic therapy consisting of palonosetron, a steroid, and aprepitant can be effective and is tolerable.

Limitations

  • Small sample (< 100)
  • Risk of bias (no control group)
  • Risk of bias (no blinding)
  • Risk of bias (no appropriate attentional control condition)
  • Key sample group differences that could influence results

 

Nursing Implications

Patients with breast cancer with highly emetogenic regimens containing both cyclophosphamide and anthracycline treated with triple therapy for resistant nausea could benefit from the addition of low-dose olanzapine.

Print

Sorooshian, H., & Vo, L. (2015). A modified olanzapine regimen for the prevention of chemotherapy-induced nausea and vomiting. The Journal of Community and Supportive Oncology, 13, 388–391. 

Study Purpose

To compare regimens using fosaprepitant and olanzapine for chemotherapy-induced nausea and vomiting (CINV) prevention

Intervention Characteristics/Basic Study Process

Patients on regimens for the prevention of CINV who were receiving highly emetogenic chemotherapy (HEC) received either a medication regimen of fosaprepitant, ondansetron, and dexamethasone, or a regimen of olanzapine, ondansetron, and dexamethasone. Those on the olanzapine regimen only received dexamethasone on day 1. Both groups had additional rescue medication as needed. All patients were assessed within 24–72 hours for CINV via follow-up phone calls, with results documented in the electronic medical record.

Sample Characteristics

  • N = 148
  • MEAN AGE = 58.47 years
  • AGE RANGE = 21–81 years
  • MALES: 53%, FEMALES: 47%
  • CURRENT TREATMENT: Chemotherapy, combination radiation and chemotherapy
  • KEY DISEASE CHARACTERISTICS: All were receiving HEC. Tumor types were not reported.
  • OTHER KEY SAMPLE CHARACTERISTICS: Of the patients, 38.5% were also receiving radiation therapy.

Setting

  • SITE: Multi-site
  • SETTING TYPE: Not specified
  • LOCATION: California

Phase of Care and Clinical Applications

  • PHASE OF CARE: Active antitumor treatment

Study Design

  • Retrospective cohort noninferiority design

Measurement Instruments/Methods

Complete response defined as no emesis after cycle 1. A difference of 15% complete response (CR) rate was used as the limit for noninferiority testing.

Results

The difference in the CR rate between groups was 8.9% in the acute phase, 12.9% in the delayed phase, and 8.6% overall. Statistical analysis showed that results in the olanzapine group were not inferior based on the difference level specified. Comparison of wholesale acquisition costs showed that the olanzapine regimen was less than 4% of the cost of the regimen using fosaprepitant ($8.58 versus $265.59).

Conclusions

The olanzapine regimen tested here was associated with less than a 15% difference in CR rate compared to a regimen containing fosaprepitant.

Limitations

  • Risk of bias (no blinding)
  • Risk of bias (no random assignment)
  • Measurement validity/reliability questionable
  • How CINV was assessed and documented is not described.
  • No subgroup analysis for those receiving concomitant radiation therapy
  • No information is provided regarding the use of breakthrough medication and any associated costs.
  • No information regarding nausea severity

Nursing Implications

This study showed that a regimen based on olanzapine was not inferior to one with fosaprepitant among patients receiving HEC if a less than 15% difference in CR rate is clinically acceptable. Individuals on the olanzapine had a higher prevalence of delayed phase CINV, though those in the olanzapine regimen also did not receive dexamethasone after day 1. The fosaprepitant regimen was much more expensive than the olanzapine regimen, so it may be a good alternative for patients with limited coverage or financial resources. Additional studies are needed to identify the most cost-effective regimens for CINV prevention, and this work needs to also provide greater focus on the prevention of nausea.

Print

Tan, L., Liu, J., Liu, X., Chen, J., Yan, Z., Yang, H., & Zhang, D. (2009). Clinical research of olanzapine for prevention of chemotherapy-induced nausea and vomiting. Journal of Experimental & Clinical Cancer Research, 28, 131.

Study Purpose

To evaluate the efficacy and safety of olanzapine compared with 5-hydroxtryptamine3 (5-HT3) receptor antagonists for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC) and to evaluate the impact of olanzapine on quality of life (QOL) of those receiving chemotherapy

Intervention Characteristics/Basic Study Process

Patients were randomized into the test group or the control group. On day 1, the test group received 10 mg oral olanzapine, 10 mg IV azasetron, and 10 mg IV dexamethasone; the control group received 10 mg IV azasetron and 10 mg IV dexamethasone. On days 2–5, the test group received 10 mg oral olanzapine and the control group received 10 mg IV dexamethasone. Patients were permitted to take other antiemetic therapy for nausea or emesis based on clinical circumstances. Assessments occurred on days 1–5 post-treatment, and QOL was measure on day 6.

Sample Characteristics

  • The study consisted of 229 participants.
  • Men in the test group had a mean age of 54 ± 9.23; women in the test group had a mean age of 48.25 ± 12.7. Men in the control group had a mean age of 54.5 ± 10.33; women in the control group had a mean age of 49.58 ± 12.12.
  • The test group was 40.5% female and 59.5% male. The control group was 40% was female and 60% male.
  • Cancer diagnoses were breast (24%), lung (23%), colorectal (13%), lymphoma (10%), stomach (9%), esophageal (5%), ovarian (5%), teratoma (2%), thymus (2%), cervical (1%), gingival (1%), glioblastoma (1%), laryngeal (1%), malignant melanoma (1%), and oropharyngeal (1%),
  • Chemotherapy agents were cisplatin (44%), oxaliplatin (23%), epirubicin (18%), adriamycin (8%), carboplatin (6%), and dacarbazine (1%).

Setting

The setting was not identified.

Phase of Care and Clinical Applications

All patients were in active treatment.

Study Design

This was a randomized controlled trial.

Measurement Instruments/Methods

  • The Common Terminology Criteria for Adverse Events, version 3 (CTAE v.3) observation table was used to grade CINV.
  • The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) was used to evaluate quality of life.

Results

  • No significant difference was noted between both groups for complete response (CR) for acute periods with HEC or MEC.
  • Respective improvement in CR occurred in the test group for delayed nausea and vomiting with HEC (39%) and MEC (25%). The whole period of nausea improved 41% with HEC and 27% with MEC (p < 0.05).
  • The olanzapine regimen protected more than two-thirds of patients from emesis after receiving HEC and MEC, thus avoiding the use of rescue therapy 2–4 days after chemotherapy.

Conclusions

Olanzapine can improve the CR of delayed nausea and vomiting and QOL in patients receiving HEC and MEC.

Limitations

  • The study was not blinded. The test group received oral medication, which the control group did not receive.
  • Other antiemetic therapies were used as needed and not monitored or factored into the analysis.
  • Validity and reliability of the measurement tools was not included.
  • Drug safety and toxicity were not defined or monitored.
  • Reporting of statistical results was unclear; the authors reported two values with each measurement (e.g., \"complete response for delayed nausea and vomiting in patients with HEC improved 39%, 22%\") without explanation of what these two measurements correspond to.
  • Discrepeancies were reported with the QOL measurements.

Nursing Implications

Olanzapine may be effective in preventing delayed CINV in patients receiving HEC or MEC, but results should be used cautiously because of poor statistical evaluation and reporting.

Print

Wang, X., Wang, L., Wang, H., & Zhang, H. (2015). Effectiveness of olanzapine combined with ondansetron in prevention of chemotherapy-induced nausea and vomiting of non-small cell lung cancer. Cell Biochemistry and Biophysics, 72, 471–473. 

Study Purpose

To compare the effects of ondansetron and olanzapine to ondansetron alone for management of chemotherapy-induced nausea and vomiting (CINV)

Intervention Characteristics/Basic Study Process

All patients received 8 mg IV ondansetron 30 minutes before chemotherapy. Patients in the experimental group also received 10 mg olanzapine for eight days. CINV was evaluated after one chemotherapy cycle.

Sample Characteristics

  • N = 84   
  • MEDIAN AGE = 60 years
  • AGE RANGE = 39–76 years
  • MALES: 72.6%, FEMALES: 37.4%
  • CURRENT TREATMENT: Chemotherapy
  • KEY DISEASE CHARACTERISTICS: All had non-small cell lung cancer and were receiving a cisplatin-gemcitabine regimen.
  • OTHER KEY SAMPLE CHARACTERISTICS: All were chemotherapy-naive.

Setting

  • SETTING TYPE: Outpatient    
  • LOCATION: China

Phase of Care and Clinical Applications

PHASE OF CARE: Active antitumor treatment

Study Design

Randomized, two-group trial

Measurement Instruments/Methods

World Health Organization toxicity grading criteria

Results

The incidence of vomiting in the acute phase was 33.33% in the olanzapine group and 54.76% in the control group (p < 0.05). The incidence of delayed CINV was 16.67% with olanzapine and 47.62% in the control group (p < 0.01).

Conclusions

The use of olanzapine as part of an antiemetic regimen was associated with a lower incidence of vomiting in the acute and delayed phases.

Limitations

  • Small sample (< 100)
  • Risk of bias (no blinding)
  • Measurement validity/reliability questionable
  • Typical antiemetic regimens were not employed. CINV was measured only in terms of vomiting, rather than control of nausea as well.

Nursing Implications

This study adds to the body of evidence demonstrating the potential role of olanzapine for control of CINV. Olanzapine may have particular benefit for control in the delayed phase. Nurses need to evaluate the patterns of CINV in patients receiving chemotherapy and can identify patients who may benefit from the use of olanzapine along with other antiemetic agents.

Print

Guideline / Expert Opinion

Frame, D.G. (2010). Best practice management of CINV in oncology patients: I. Physiology and treatment of CINV. Multiple neurotransmitters and receptors and the need for combination therapeutic approaches. Journal of Supportive Oncology, 8(2, Suppl. 1), 5–9.

Results Provided in the Reference

  • This article reviewed the neurotransmitter and receptor systems involved with chemotherapy-induced nausea and vomiting (CINV) and a brief history of development of antiemetic therapies. CINV classifications was defined as follows.
    • Acute—occurring and resolving within 24 hours of chemotherapy
    • Delayed—occurring more than 24 hours after chemotherapy administration
    • Breakthrough—occurring despite antiemetic therapy
    • Refractory—unmanageable with current antiemetics
    • Anticipatory—conditioned response after prior inadequately controlled CINV.
  • The article stated that anticipatory CINV is the most common kind.
  • The article reviewed the mechanism of action and current knowledge regarding common antiemetic regimens and noted that given the physiology involved, optimal treatment requires a combination of therapies targeting multiple systems.

Guidelines & Recommendations

  • Dexamethasone in combination with 5-HT3 receptor antagonists is recommended (unless contraindicated or not tolerated). The author noted that this is too often not included.
  • In delayed emesis, metoclopramide has been shown to be equivalent to ondansetron in controlling delayed CINV. Metoclopramide is also associated with extrapyramidal symptoms.
  • Differences among 5-HT3 receptor antagonists were noted.
    • Among first generation drugs, overall efficacy of the agents are similar.
    • Palonosetron is a second generation drug with a longer half-life, which appears to be associated with some preventive benefits.
    • Results of studies indicate that without some combination therapy, these drugs alone will fail in 40%–50% of patients.
    • The author noted that some individuals have a genetic tendency to metabolize these drugs differently and those with ultra-rapid metabolism have less therapeutic benefit. Palonosetron appears to have a smaller effect in this area.
  • The effects of 2 mg per day of oral granisetron and 3.1 mg per day via epidermal patch appear to be similar.
  • The addition of aprepitant (a neurokinin 1 [NK1] antagonist) to 5-HT3 receptor antagonists and dexamethasone has demonstrated success. A larger benefit has been found for women than for men. The current approved regimen for aprepitant is a three-day regimen; however, ongoing studies are under way to determine if additional doses are helpful. When using aprepitant, the dexamethasone dosage should be reduced. A potential interaction between aprepitant and chemotherapeutic agents such as ifosfamide have been noted. In one study, the combination was associated with increased neurotoxicity.
  • Olanzapine is an antipsychotic that blocks multiple neurotransmitters involved in CINV. Trials of olanzapine in combination with granisetron plus dexamethasone and palonosetron plus dexamethasone have demonstrated effectiveness in preventing CINV.

Nursing Implications

This article demonstrated the importance of combination therapy for prevention and management of CINV. The author provides a good overview of relevant physiology, mechanism of action of current agents, and current regimens used. The article points to the need for additional research with the use of olanzapine for CINV.

Print

National Comprehensive Cancer Network. (2016). NCCN Clinical Practice Guidelines in Oncology: Antiemesis [v.2.2016]. Retrieved from http://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf

Purpose & Patient Population

PURPOSE: To provide guidance in the prevention and management of nausea and vomiting in patients with cancer
 
TYPES OF PATIENTS ADDRESSED: It is unclear if recommendations are intended to apply to pediatric as well as to adult patients

Type of Resource/Evidence-Based Process

RESOURCE TYPE: Evidence-based guideline

PROCESS OF DEVELOPMENT: Expert panel reviews selected evidence from literature to update guidelines.   
 
DATABASES USED: PubMed
 
INCLUSION CRITERIA: Clinical trials, guidelines, systematic reviews, meta-analysis, English language
 
EXCLUSION CRITERIA: Not specified

Phase of Care and Clinical Applications

PHASE OF CARE: Multiple phases of care

Results Provided in the Reference

One hundred seventy-one articles were retrieved via aPubMed search. No information was provided regarding which articles were selected as relevant to these guidelines, and no discussion of any method used for rating the quality of included evidence exists.

Guidelines & Recommendations

For high emetic risk (HEC) and moderate risk (MEC), recommendations include a standard triple drug antiemetic regimen, a NEPA-containing regimen, or a olanzapine-based triple drug regimen in which olanzapine is used in place of an NK1 and no dexamethasone is given after day 1.
 
For breakthrough treatment, recommendations suggest olanzapine, benzodiazepine, cannabinoid, phenothiazine, 5HT3, dexamethasone, haloperidol, metoclopramide, or a scopolamine transdermal patch. Recommendations include using a regimen for higher level emetogenicity prior to subsequent cycles or changing between aprepitant-based and olanzapine-based regimens.
 
For anticipatory CINV, recommendations suggests relaxation, hypnosis, guided imagery, music therapy, acupuncture, acupressure, or anxiolytics.

Limitations

Limited database used. Recommendations are a combination of evidence- and consensus-based suggestions, and most nonpharmacologic interventions are by consensus.

Nursing Implications

Provides multiple evidence- and consensus-based recommendations for prophylaxis and the management of nausea and vomiting due to chemotherapy or radiation therapy. Recommendations provide a list of chemotherapy agents, including oral agents and categorization as to emetic potential.

Print

Wickham, R. (2010). Best practice management of CINV in oncology patients: II. Antiemetic guidelines and rationale for use. Journal of Supportive Oncology, 8(2, Suppl. 1), 10–15.

Type of Resource/Evidence-Based Process

The search strategy was not applicable or stated.

Results Provided in the Reference

This article discussed underlying shared principles in chemotherapy-induced nausea and vomiting (CINV) guidelines from the American Society of Clinical Oncology (ASCO), the Multinational Association for Supportive Care in Cancer (MASCC), and the National Comprehensive Cancer Network (NCCN).

  • Common goals among these guidelines are to prevent CINV and to identify the risk period for CINV asscociated with at least four days of moderate- and high-intensity emetogenic treatments.
  • The guidelines report that oral and IV formulations of 5-HT3 receptor antagonists are equally effective.
  • Selection of an antiemetic regimen should be based on the emetic risk of the chemotherapy being used as well as patient factors and experience.
  • Prophylactic antiemetics should be used when the risk of CINV is 10% or more.
  • A table of chemotherapeutic medications by emetogenic risk was provided. The author noted that such risk assignment does not provide for moving up the CINV risk ladder according to differing patient experience. Current guidelines are similar in terms of antiemetic regimens but only outline this for the first course of chemotherapy.
  • The article provided a brief review of current specific antiemetic recommendations provided in guidelines. Substantial differences exist between physician and nursing assignment of patient risk for delayed CINV, and limited evidence exists regarding the best approaches for breakthrough CINV.

Guidelines & Recommendations

Currently recommended agents for breakthrough CINV are prochlorperazine, metoclopramide with or without diphenhydramine, haloperidol, dexamethasone, dronabinol nabilone, lorazepam, alternating 5-HT3 receptor antagonists, olanzapine, and promethazine. The author noted that guidelines are useful, but guideline adherence can only go to a certain extent in preventing CINV, particularly with delayed symptoms, multiple-day chemotherapeutic regimens, high-dose chemotherapy, breakthrough CINV, and refractory CINV.

Nursing Implications

CINV guidelines are a good clinical tool to help clinicians implement evidence-based practice; however, their use needs to be accompanied by accurate patient assessments throughout the period of CINV risk. A standard guideline may not fit the needs of all patients and recommendations need to be viewed as a starting point for individualized patient care. More study and attention needs to be given to issues of delayed, breakthrough, and refractory CINV. This article is expert opinion-based and does not provide evidence for all information provided.

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