Olanzapine for the Treatment of Advanced Cancer–Related Chronic Nausea and/or Vomiting: A Randomized Pilot Trial | Oncology | JAMA Oncology | JAMA Network
[Skip to Navigation]
Sign In
Visual Abstract. Olanzapine for the Treatment of Advanced Cancer–Related Chronic Nausea and/or Vomiting
Olanzapine for the Treatment of Advanced Cancer–Related Chronic Nausea and/or Vomiting
Figure 1.  CONSORT Diagram
CONSORT Diagram

Data regarding eligibility assessment were not collected. All entered patients received the appropriate randomly assigned intervention, and no patients were lost to follow-up. All patients were included in the analyses.

aOne patient stopped the study medication on day 5 owing to nausea, which was allowed by the protocol.

Figure 2.  Plots of Daily Data Over Time
Plots of Daily Data Over Time

Plots with 95% CIs, regarding daily data during the study period for numeric rating score (NRS) for nausea (A), the number of emetogenic episodes per day (B), the number of rescue antiemetic doses per day (C), and NRS for well-being (D). In some plots, lower scores are better, while higher scores are better in others; in all situations, the olanzapine arm had more favorable results. The provided P values are from the Wilcoxon test in which change from baseline to day 7 was tested between arms.

Table.  Protocol-Derived Data at Baseline and for the 24 Hours After the First and Last Study Doses of Olanzapine
Protocol-Derived Data at Baseline and for the 24 Hours After the First and Last Study Doses of Olanzapine
1.
Delgado-Guay  MO, Parsons  HA, Li  Z, Palmer  LJ, Bruera  E.  Symptom distress, interventions, and outcomes of intensive care unit cancer patients referred to a palliative care consult team.   Cancer. 2009;115(2):437-445. doi:10.1002/cncr.24017PubMedGoogle ScholarCrossref
2.
Digges  M, Hussein  A, Wilcock  A,  et al.  Pharmacovigilance in hospice/palliative care: net effect of haloperidol for nausea or vomiting.   J Palliat Med. 2018;21(1):37-43. doi:10.1089/jpm.2017.0159PubMedGoogle ScholarCrossref
3.
Gupta  M, Davis  M, LeGrand  S, Walsh  D, Lagman  R.  Nausea and vomiting in advanced cancer: the Cleveland Clinic protocol.   J Support Oncol. 2013;11(1):8-13. doi:10.1016/j.jpainsymman.2012.10.042PubMedGoogle Scholar
4.
Bruera  E, Moyano  JR, Sala  R,  et al.  Dexamethasone in addition to metoclopramide for chronic nausea in patients with advanced cancer: a randomized controlled trial.   J Pain Symptom Manage. 2004;28(4):381-388. doi:10.1016/j.jpainsymman.2004.01.009PubMedGoogle ScholarCrossref
5.
Jackson  WC, Tavernier  L.  Olanzapine for intractable nausea in palliative care patients.   J Palliat Med. 2003;6(2):251-255. doi:10.1089/109662103764978506PubMedGoogle ScholarCrossref
6.
Licup  N.  Olanzapine for nausea and vomiting.   Am J Hosp Palliat Care. 2010;27(6):432-434. doi:10.1177/1049909110369532PubMedGoogle ScholarCrossref
7.
Passik  SD, Kirsh  KL, Theobald  DE,  et al.  A retrospective chart review of the use of olanzapine for the prevention of delayed emesis in cancer patients.   J Pain Symptom Manage. 2003;25(5):485-488. doi:10.1016/S0885-3924(03)00078-2PubMedGoogle ScholarCrossref
8.
Passik  SD, Lundberg  J, Kirsh  KL,  et al.  A pilot exploration of the antiemetic activity of olanzapine for the relief of nausea in patients with advanced cancer and pain.   J Pain Symptom Manage. 2002;23(6):526-532. doi:10.1016/S0885-3924(02)00391-3PubMedGoogle ScholarCrossref
9.
Pirl  WF, Roth  AJ.  Remission of chemotherapy-induced emesis with concurrent olanzapine treatment: a case report.   Psychooncology. 2000;9(1):84-87. doi:10.1002/(SICI)1099-1611(200001/02)9:1<84::AID-PON440>3.0.CO;2-TPubMedGoogle ScholarCrossref
10.
Srivastava  M, Brito-Dellan  N, Davis  MP, Leach  M, Lagman  R.  Olanzapine as an antiemetic in refractory nausea and vomiting in advanced cancer.   J Pain Symptom Manage. 2003;25(6):578-582. doi:10.1016/S0885-3924(03)00143-XPubMedGoogle ScholarCrossref
11.
Kaneishi  K, Kawabata  M, Morita  T.  Olanzapine for the relief of nausea in patients with advanced cancer and incomplete bowel obstruction.   J Pain Symptom Manage. 2012;44(4):604-607. doi:10.1016/j.jpainsymman.2011.10.023PubMedGoogle ScholarCrossref
12.
Harder  S, Groenvold  M, Isaksen  J,  et al.  Antiemetic use of olanzapine in patients with advanced cancer: results from an open-label multicenter study.   Support Care Cancer. 2019;27(8):2849-2856. doi:10.1007/s00520-018-4593-3PubMedGoogle ScholarCrossref
13.
MacKintosh  D.  Olanzapine in the management of difficult to control nausea and vomiting in a palliative care population: a case series.   J Palliat Med. 2016;19(1):87-90. doi:10.1089/jpm.2015.0224PubMedGoogle ScholarCrossref
14.
Navari  RM, Brenner  MC.  Treatment of cancer-related anorexia with olanzapine and megestrol acetate: a randomized trial.   Support Care Cancer. 2010;18(8):951-956. doi:10.1007/s00520-009-0739-7PubMedGoogle ScholarCrossref
15.
Navari  RM, Qin  R, Ruddy  KJ,  et al.  Olanzapine for the prevention of chemotherapy-induced nausea and vomiting.   N Engl J Med. 2016;375(2):134-142. doi:10.1056/NEJMoa1515725PubMedGoogle ScholarCrossref
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    1 Comment for this article
    EXPAND ALL
    Olanzapine for the treatment of advanced cancer-related chronic nausea and/or vomiting
    Tomoyuki Kawada, MD | Nippon Medical School
    Navari et al. conducted a double-blind randomized clinical trial (RCT) to evaluate the utility of olanzapine 5 mg for treating chronic nausea/vomiting in outpatients with advanced cancer (1). They had no chemotherapy or radiotherapy in the prior 14 days. Olanzapine was effective in controlling nausea and emesis and in improving other symptoms and quality-of-life parameters. In addition, there was no excess sedation or any other adverse events in this study. I have some comments regarding this study.

    Harder et al. investigated the antiemetic effect and tolerability of olanzapine 10 mg in 40 patients with advanced cancer not receiving chemotherapy
    or irradiation (2). Thirty-six patients experienced some degree of improvement, although the dose of olanzapine was reduced in three patients due to adverse events. They recommended RCT with use of 5 or 2.5 mg olanzapine to evaluate whether it is effective and tolerable as an antiemetic drug in patients with advanced cancer. I suppose that Navari et al. reported a subsequent outcome to check the change in adverse effect by low dose of olanzapine.

    Regarding the efficacy of olanzapine for the prevention of chemotherapy-induced nausea and vomiting, Navari had conducted double-blind RCT, and olanzapine 10 mg significantly improved nausea prevention (3). Although there were no grade 5 toxic effects, some patients receiving olanzapine had increased sedation. I suspect that lower dose of olanzapine might have different effects on nausea prevention and sedation. On this point, Hashimoto et al. conducted a double-blind RCT to evaluate the efficacy of olanzapine 5 mg combined with standard antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting caused by cisplatin-based chemotherapy (4), which might also be intended to prevent sedation. A complete response, which was defined as absence of vomiting and no use of rescue medications in the delayed phase (24-120 h), was 79% [95% CI 75-83] in the olanzapine group and 66% [95% CI 61-71] in the placebo group. They concluded that olanzapine 5 mg combined with aprepitant, palonosetron, and dexamethasone could be an effective antiemetic therapy in patients with cisplatin-based chemotherapy.

    Anyway, efficacy of low dose olanzapine therapy for the prevention of nausea/vomiting should be further evaluated by RCT.


    References
    1. Navari RM, Pywell CM, Le-Rademacher JG, et al. Olanzapine for the treatment of advanced cancer-related chronic nausea and/or vomiting: A randomized pilot trial. JAMA Oncol. 2020 Jun 1;6(6):895-899.
    2. Harder S, Groenvold M, Isaksen J, et al. Antiemetic use of olanzapine in patients with advanced cancer: results from an open-label multicenter study. Support Care Cancer. 2019 Aug;27(8):2849-2856.
    3. Navari RM, Qin R, Ruddy KJ, et al. Olanzapine for the prevention of chemotherapy-induced nausea and vomiting. N Engl J Med. 2016 Jul 14;375(2):134-42.
    4. Hashimoto H, Abe M, Tokuyama O, et al. Olanzapine 5 mg plus standard antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting (J-FORCE): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 Feb;21(2):242-249.
    CONFLICT OF INTEREST: None Reported
    READ MORE
    Brief Report
    May 7, 2020

    Olanzapine for the Treatment of Advanced Cancer–Related Chronic Nausea and/or Vomiting: A Randomized Pilot Trial

    Author Affiliations
    • 1Comprehensive Cancer Center, University of Alabama at Birmingham
    • 2Mayo Clinic, Rochester, Minnesota
    • 3Washington University School of Medicine, St Louis, Missouri
    • 4Indiana University School of Medicine, Indianapolis
    JAMA Oncol. 2020;6(6):895-899. doi:10.1001/jamaoncol.2020.1052
    Key Points

    Question  Does olanzapine decrease nausea/vomiting, independent of chemotherapy, in patients with advanced cancer?

    Findings  In this small, double-blinded, randomized, placebo-controlled clinical trial, olanzapine treatment demonstrated a statistically significant decrease in nausea and vomiting and was well tolerated.

    Meaning  While olanzapine looks as promising as any other drug for decreasing nausea and/or vomiting in patients with advanced cancer, the small sample size begs for additional testing.

    Abstract

    Importance  Nausea and vomiting, unrelated to chemotherapy, can be substantial symptoms in patients with advanced cancer.

    Objective  To evaluate the utility of olanzapine for treating chronic nausea/vomiting, unrelated to chemotherapy, in patients with advanced cancer.

    Design, Setting, and Participants  This study is a double-line, placebo-controlled, randomized clinical trial conducted from July 2017 through April 2019, with analysis conducted in 2019. Eligible participants were outpatients with advanced cancer who had persistent nausea/vomiting without having had chemotherapy or radiotherapy in the prior 14 days. Chronic nausea was present for at least 1 week (worst daily nausea numeric rating scores needed to be greater than 3 on a 0-10 scale).

    Interventions  Patients received olanzapine (5 mg) or a placebo, orally, daily for 7 days.

    Main Outcomes and Measures  Patient-reported outcomes were used for study end points. Data were collected at baseline and daily for 7 more days. The primary study end point (the change in nausea numeric rating scores from baseline to the last treatment day) and the study hypothesis were both identified prior to data collection.

    Results  A total of 30 patients (15 per arm) were enrolled; these included 16 women and 14 men who had a mean (range) age of 63 (39-79) years. Baseline median nausea scores, in all patients, were 9 out of 10 (range, 8-10). After 1 day and 1 week, the median nausea scores in the placebo arm were 9 out of 10 (range, 8-10) on both days, compared with the olanzapine arm scores of 2 out of 10 (range, 2-3) after day 1 and 1 out of 10 (range, 0-3) after 1 week. After 1 week of treatment, the reduction in nausea scores in the olanzapine arm was 8 points (95% CI, 7-8) higher than that of the placebo arm. The primary 2-sided end point P value was <.001. Correspondingly, patients in the olanzapine arm reported less emesis, less use of other antiemetic drugs, better appetite, less sedation, less fatigue, and better well-being. One patient, on the placebo, stopped treatment early owing to lack of perceived benefit. No patients receiving olanzapine reported excess sedation or any other adverse event.

    Conclusions and Relevance  Olanzapine, at 5 mg/d, appeared to be effective in controlling nausea and emesis and in improving other symptoms and quality-of-life parameters in the study population.

    Trial Registration  ClinicalTrials.gov Identifier: NCT03137121

    Introduction

    Chronic nausea is a particularly distressing, multifactorial symptom reported to be present in many patients with advanced cancer. There is very limited information from randomized clinical trials evaluating effective palliative options for this problem.1-4

    Case reports, small retrospectively evaluated series, and a prospective pilot exploration support that olanzapine may be effective for the relief of nausea/vomiting, unrelated to chemotherapy, in patients with advanced cancer.5-11 On that basis, it was hypothesized that olanzapine would be an effective treatment of chronic nausea/vomiting in patients with advanced cancer, leading to the conduct of the currently reported trial.

    Methods

    Adult patients with malignant disease in an advanced, incurable stage were considered for this trial. They could not have had received chemotherapy or radiotherapy during the preceding 14 days or antipsychotic medications within the previous 30 days, nor had either of these planned for the duration of the study. Each eligible patient had chronic nausea that had been present for at least 1 week (worst daily score of >3 on a 0-10 numeric rating score). All patients provided written informed consent approved by internal review boards from each participating institution, per US federal guidelines. The trial was approved by the institutional review boards of all participating institutions (Mayo Clinic, University of Indiana, University of Alabama at Birmingham, and Washington University). The trial protocol is provided in Supplement 1.

    Protocol patients were randomized to receive olanzapine (5 mg/d, orally, days 1-7) or a placebo. All clinicians interacting with patients and all patients were blinded (eAppendix in Supplement 2). Patients were permitted to use alternative antiemetics (any rescue therapy as determined by the patient’s clinician) if persistent nausea and/or emesis or retching had not remitted with the assigned study treatment.

    Patients had a baseline evaluation that included assessment of symptom intensity for appetite, nausea, fatigue, sedation, and pain, all measured on a numeric rating score. For each of these symptoms, patients were asked to circle the one number (0-10, from none to a substantial amount of each item) that best described the way they felt over the preceding 24 hours. The number of vomiting episodes in the preceding 24 hours was also recorded. Well-being was recorded on a 0 to 10 numeric rating score (0 indicated the worst possible; 10, best possible).

    For 7 days, at approximately the same time each day, patients were asked to report the intensity of appetite, nausea, fatigue, sedation, and pain, as well as overall well-being, using numeric rating scores; additionally, they reported the number of vomiting episodes in the previous 24 hours and also reported the use of the daily dose of the study drug in a medication log and the use of any rescue medications for nausea/vomiting. To facilitate patient completion of the patient-reported outcome tools, a nurse/research coordinator contacted each patient every day to remind participants to complete study materials and to query about toxic effects.

    The primary objective of this trial was to estimate the effect of olanzapine vs placebo on chronic nausea and vomiting. The selected primary end point was the change in nausea scores from baseline to the last treatment day using a numeric rating score. Nausea, appetite, fatigue, sedation, pain, and well-being numeric rating scores were summarized by median and range separately by treatment arm. The number of emesis episodes at each time point and change scores from baseline to 24 hours and to 7 days after treatment initiation were also summarized by median and range separately by treatment arm. The score changes from baseline to 7 days after treatment were compared between arms using the Wilcoxon rank sum test. All provided P values are from exact 2-sided Wilcoxon rank sum tests, with values less than .05 considered significant. The difference in nausea score changes and the change in the number of emesis episodes, from baseline to the last treatment day, between the 2 arms were estimated with 95% CIs using the Hodges-Lehmann method. The repeated measurements of all numeric rating score domains, doses of alternative antiemetic drugs, and vomiting over time were plotted by treatment arms. Statistical analyses were performed with R, version 3.6.2 (R Project for Statistical Computing). This study followed the Consolidated Standards of Reporting Trials (CONSORT) reporting guideline.

    Results

    A total of 30 outpatients, 16 women and 14 men with a mean (range) age of 63 (39-79) years, were enrolled in the study from 3 institutions (University of Alabama at Birmingham, Washington University, and Indiana University) from July 2017 through April 2019. A CONSORT diagram is depicted in Figure 1. The eTable in Supplement 2 summarizes the on-study patient demographic information.

    One patient, who was on the placebo arm, withdrew from the study on day 5 owing to persistent nausea/vomiting. As the patient’s symptoms persisted without improvement at the time of study withdrawal, the patient’s symptom scores from the last visit were carried forward for the last 2 study days.

    The Table provides the baseline and outcome data for this trial. Race/ethnicity information was obtained by study coordinators as part of standard procedure. Figure 2 illustrates daily data at baseline and during the study period for nausea numeric rating scores (A), the number of emesis episodes per day (B), the number of rescue antiemetic doses per day (C), and well-being numeric rating scores (D). After 1 week of treatment, the reduction in nausea scores in the olanzapine arm was 8 points (95% CI, 7-8) higher than that of the placebo arm (P < .001).

    When the study was completed, a question arose as to how long the perceived benefit from olanzapine might last. While the protocol was only designed as a 7-day study, at the end of the 7 days, the protocol code was broken and patients on olanzapine were allowed to receive olanzapine as a prescription medication from their attending clinician. Months after the protocol was completed, the protocol patients’ clinicians were contacted to inquire about how the patients did following study participation. The results of this inquiry revealed that all the patients on olanzapine continued on it at 5 mg/d, with continued efficacy and no toxic effects attributed to the olanzapine. Of the 14 patients who were initially receiving a placebo, all were offered olanzapine at 5 mg/d; 13 began olanzapine treatment, while 1 patient declined owing to disease progression and inability to take oral medications. All these patients reported marked efficacy and few or no toxic effects. All patients continued olanzapine for 3 to 12 weeks, with reasons for discontinuing olanzapine, in both groups, being disease progression, an inability to take oral medications, or death.

    Discussion

    This trial supports the prestudy hypothesis that olanzapine is effective for the treatment of chronic nausea and vomiting in patients with advanced cancer. The magnitude of benefit observed in this trial, regarding nausea/vomiting, is in line with what has been reported in 3 other pilot reports.8,12,13

    The patient-reported data support that the 5 mg daily olanzapine dose was well tolerated. The improvement in appetite is not surprising, as the appetite-enhancing properties of this drug are well known.14 With olanzapine being associated with undesired sedation in some situations,15 it is interesting to note that there was decreased sedation and improved fatigue in the olanzapine arm. Potential explanations for this are that a relatively low dose of olanzapine was given and also that patients receiving olanzapine had a decrease in the use of other antiemetic medications, which may have caused a sedating effect in the placebo arm.

    Limitations

    The small sample size in the current trial is clearly a study limitation. Further data regarding the utility of olanzapine for controlling nausea and vomiting in patients with advanced cancer are welcomed.

    Conclusions

    The data from this trial support that olanzapine substantially decreases nausea/vomiting associated with advanced cancer and is relatively well tolerated. No other drug studied in this situation has been reported to decrease nausea/vomiting more than was observed in this study.

    Back to top
    Article Information

    Accepted for Publication: March 6, 2020.

    Corresponding Author: Charles L. Loprinzi, MD, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (cloprinzi@mayo.edu).

    Published Online: May 7, 2020. doi:10.1001/jamaoncol.2020.1052

    Author Contributions: Drs Navari and Le-Rademacher had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All of the information and materials in the manuscript are original.

    Study concept and design: Navari, Le-Rademacher, Albany, Loprinzi.

    Acquisition, analysis, or interpretation of data: All authors.

    Drafting of the manuscript: Navari, Le-Rademacher, Albany, Loprinzi.

    Critical revision of the manuscript for important intellectual content: All authors.

    Statistical analysis: Navari, Le-Rademacher, Dodge.

    Obtained funding: Navari.

    Administrative, technical, or material support: Navari, White.

    Study supervision: Navari, Loprinzi.

    Conflict of Interest Disclosures: Dr Le-Rademacher reported receiving grants from Mayo Clinic during the conduct of the study. Dr Albany reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Loprinzi reported receiving grants from the National Cancer Institute during the conduct of the study, and personal fees from PledPharma, Disarm Therapeutics, Asahi Kasei, Metys Pharmaceuticals, OnQuality Pharmaceuticals, Mitsubishi Tanabe Pharma, and NKMax outside the submitted work. No other disclosures were reported.

    Funding/Support: This work was supported by the National Cancer Institute of the National Institutes of Health under the award No. UG1CA189823 to the Alliance for Clinical Trials in Oncology NCI Community Oncology Research Program Research Base (Jan C. Buckner, MD, contact PI). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

    Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and decision to submit the manuscript for publication. The funder had no role in the preparation, review, or approval of the manuscript, except the Alliance for Clinical Trials in Oncology manuscript review team read the manuscript, made suggestions on citing the grant award that funded the study, and made some editorial suggestions to make the manuscript read better.

    Data Sharing Statement: See Supplement 3.

    References
    1.
    Delgado-Guay  MO, Parsons  HA, Li  Z, Palmer  LJ, Bruera  E.  Symptom distress, interventions, and outcomes of intensive care unit cancer patients referred to a palliative care consult team.   Cancer. 2009;115(2):437-445. doi:10.1002/cncr.24017PubMedGoogle ScholarCrossref
    2.
    Digges  M, Hussein  A, Wilcock  A,  et al.  Pharmacovigilance in hospice/palliative care: net effect of haloperidol for nausea or vomiting.   J Palliat Med. 2018;21(1):37-43. doi:10.1089/jpm.2017.0159PubMedGoogle ScholarCrossref
    3.
    Gupta  M, Davis  M, LeGrand  S, Walsh  D, Lagman  R.  Nausea and vomiting in advanced cancer: the Cleveland Clinic protocol.   J Support Oncol. 2013;11(1):8-13. doi:10.1016/j.jpainsymman.2012.10.042PubMedGoogle Scholar
    4.
    Bruera  E, Moyano  JR, Sala  R,  et al.  Dexamethasone in addition to metoclopramide for chronic nausea in patients with advanced cancer: a randomized controlled trial.   J Pain Symptom Manage. 2004;28(4):381-388. doi:10.1016/j.jpainsymman.2004.01.009PubMedGoogle ScholarCrossref
    5.
    Jackson  WC, Tavernier  L.  Olanzapine for intractable nausea in palliative care patients.   J Palliat Med. 2003;6(2):251-255. doi:10.1089/109662103764978506PubMedGoogle ScholarCrossref
    6.
    Licup  N.  Olanzapine for nausea and vomiting.   Am J Hosp Palliat Care. 2010;27(6):432-434. doi:10.1177/1049909110369532PubMedGoogle ScholarCrossref
    7.
    Passik  SD, Kirsh  KL, Theobald  DE,  et al.  A retrospective chart review of the use of olanzapine for the prevention of delayed emesis in cancer patients.   J Pain Symptom Manage. 2003;25(5):485-488. doi:10.1016/S0885-3924(03)00078-2PubMedGoogle ScholarCrossref
    8.
    Passik  SD, Lundberg  J, Kirsh  KL,  et al.  A pilot exploration of the antiemetic activity of olanzapine for the relief of nausea in patients with advanced cancer and pain.   J Pain Symptom Manage. 2002;23(6):526-532. doi:10.1016/S0885-3924(02)00391-3PubMedGoogle ScholarCrossref
    9.
    Pirl  WF, Roth  AJ.  Remission of chemotherapy-induced emesis with concurrent olanzapine treatment: a case report.   Psychooncology. 2000;9(1):84-87. doi:10.1002/(SICI)1099-1611(200001/02)9:1<84::AID-PON440>3.0.CO;2-TPubMedGoogle ScholarCrossref
    10.
    Srivastava  M, Brito-Dellan  N, Davis  MP, Leach  M, Lagman  R.  Olanzapine as an antiemetic in refractory nausea and vomiting in advanced cancer.   J Pain Symptom Manage. 2003;25(6):578-582. doi:10.1016/S0885-3924(03)00143-XPubMedGoogle ScholarCrossref
    11.
    Kaneishi  K, Kawabata  M, Morita  T.  Olanzapine for the relief of nausea in patients with advanced cancer and incomplete bowel obstruction.   J Pain Symptom Manage. 2012;44(4):604-607. doi:10.1016/j.jpainsymman.2011.10.023PubMedGoogle ScholarCrossref
    12.
    Harder  S, Groenvold  M, Isaksen  J,  et al.  Antiemetic use of olanzapine in patients with advanced cancer: results from an open-label multicenter study.   Support Care Cancer. 2019;27(8):2849-2856. doi:10.1007/s00520-018-4593-3PubMedGoogle ScholarCrossref
    13.
    MacKintosh  D.  Olanzapine in the management of difficult to control nausea and vomiting in a palliative care population: a case series.   J Palliat Med. 2016;19(1):87-90. doi:10.1089/jpm.2015.0224PubMedGoogle ScholarCrossref
    14.
    Navari  RM, Brenner  MC.  Treatment of cancer-related anorexia with olanzapine and megestrol acetate: a randomized trial.   Support Care Cancer. 2010;18(8):951-956. doi:10.1007/s00520-009-0739-7PubMedGoogle ScholarCrossref
    15.
    Navari  RM, Qin  R, Ruddy  KJ,  et al.  Olanzapine for the prevention of chemotherapy-induced nausea and vomiting.   N Engl J Med. 2016;375(2):134-142. doi:10.1056/NEJMoa1515725PubMedGoogle ScholarCrossref
    ×