olanzapine and Nausea

Several regimens have been introduced in clinical practice in the last twenty years to treat chemotherapy-induced nausea and vomiting (CINV). However, direct comparative data remain insufficient, as many new regimes lack head-to-head comparisons. In this study, through an indirect comparison, we overcome this limit by providing the most up-to-date estimate of the efficacy and safety of all combinations used for HEC-induced nausea and vomiting.. We retrieved randomized controlled trials (RCTs) published in Pubmed, Embase, and Cochrane Library until June, 30th 2022. We included phase II-III RCTs, including adults with any cancer receiving HEC, and compared different antiemetic regimes to prevent CINV. The primary outcome was the overall complete response (defined as the absence of vomiting and of the use of rescue drugs from 0 to 120 hrs since chemotherapy); secondary outcomes were acute (absence of vomiting and use of rescue medicine 0-24 hrs after chemotherapy) and delayed (24-120 hrs) response and adverse events.. A total of 53 RCTs enrolling 22 228 patients were included. We classified the different antiemetic regimes into 21 different groups. Overall, 3- or 4-drug regimens containing a combination of dexamethasone, 5HT3 antagonists, mirtazapine or olanzapine with or without NK antagonists, yielded the highest probability to be the most effective regimen in terms of complete response. Regimens containing a combination of dexamethasone and 5-HT3 antagonist have the lowest probability of being the most effective regimen in terms of complete, acute, and delayed response.. In our network meta-analysis, 4-drug regimens with olanzapine displayed the highest probability of efficacy in terms of complete response. A 3-drug regimen with olanzapine represents a valid option in a limited resource context.

Topics: Adult; Antiemetics; Antineoplastic Agents; Dexamethasone; Humans; Nausea; Network Meta-Analysis; Olanzapine; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) remain the most distressing event in patients receiving highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC). This meta-analysis was conducted to evaluate the efficacy and safety of olanzapine containing regimen in preventing CINV in children on HEC and MEC. We searched PubMed, Embase, and Cochrane central register of controlled trials electronic databases to identify randomized clinical trials that compared 2 groups who either got olanzapine (olanzapine group) or placebo/no olanzapine (control group) for the prevention of CINV in children. The primary outcome was to determine the efficacy of olanzapine (complete response). The secondary outcomes were nausea control, the need for rescue medications, and adverse events of olanzapine. Three randomized clinical trials (n=394 patients) were included in this meta-analysis (olanzapine group, n=194, and placebo/control group, n=200). The pooled analysis of this meta-analysis found that olanzapine had a higher complete response in all phases of emesis in the HEC group and only in the acute phase in HEC/MEC groups compared with the control group. Olanzapine had higher nausea control in all phases of HEC but no nausea control in HEC/MEC. Olanzapine also reduced the need for rescue medications. A significant number of patients in the olanzapine group experienced somnolence (grades 1 and 2), but none of the participants discontinued the study due to side effects. In conclusion, this meta-analysis showed that olanzapine significantly prevented CINV in HEC. There was also a lesser need for rescue medications in the olanzapine group. Somnolence was higher in the olanzapine group, but it was clinically insignificant.

Topics: Antiemetics; Antineoplastic Agents; Child; Humans; Nausea; Neoplasms; Olanzapine; Randomized Controlled Trials as Topic; Sleepiness; Vomiting

Topics: Antiemetics; Antineoplastic Agents; Benzodiazepines; Humans; Nausea; Network Meta-Analysis; Olanzapine; Vomiting

Olanzapine is an effective antipsychotic drug used in psychiatry to treat psychoses, especially schizophrenia and schizoaffective disorders. It belongs to the 2nd generation antipsychotics, its mechanism of action ranks among multireceptor antagonists (MARTA); it affects the dopamine, serotonin, adrenaline, histamine, and muscarinic systems. The broad pharmacodynamic profile of olanzapine provides for a broad indication spectrum with a better adverse effect profile compared to conventional antipsychotics. It can be used in a number of situations to benefit cancer patients in palliative care as well as in the terminal stages of the disease.. The review article presents possible indications for olanzapine in oncological palliative care. Apart from dealing with delirium and anxiety, indications for the use of antipsychotics in palliative medicine include the management of nausea, vomiting and loss of appetite. Olanzapine is an effective antiemetic in cancer patients with tumor-induced nausea and in antiemetic regimens for chemotherapy-induced nausea and vomiting. Olanzapine is an effective treatment for delirium, as effective as haloperidol, but with a lower toxicity profile. It increases appetite and can be used with advantage in patients with anorexia and weight loss. It is possible to use its anxiolytic and mood-stabilizing effects; in many situations, it can serve well as a co-analgesic, especially in the so-called total pain. It is proven to increase the quality of life of patients with advanced cancer.. Due to its effect, simple dosage and a good safety profile, olanzapine is a useful drug for the routine clinical practice of an oncologist - a non-psychiatrist.

Topics: Antiemetics; Antipsychotic Agents; Delirium; Humans; Nausea; Neoplasms; Olanzapine; Palliative Care; Quality of Life; Vomiting

Pharmacological interventions for disordered and problem gambling have been employed in clinical practice. Despite the availability of several reviews of the efficacy of pharmacological interventions for disordered or problem gambling, few have employed systematic search strategies or compared different categories of pharmacological interventions. Systematic reviews of high-quality evidence are therefore essential to provide guidance regarding the efficacy of different pharmacological interventions for disordered or problem gambling.. The primary aims of the review were to: (1) examine the efficacy of major categories of pharmacological-only interventions (antidepressants, opioid antagonists, mood stabilisers, atypical antipsychotics) for disordered or problem gambling, relative to placebo control conditions; and (2) examine the efficacy of these major categories relative to each other.  SEARCH METHODS: We searched the Cochrane Common Mental Disorders Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase, and PsycINFO (all years to 11 January 2022).. We included randomised trials evaluating a pharmacological intervention for the treatment of disordered or problem gambling. Eligible control conditions included placebo control groups or comparisons with another category of pharmacological intervention.. We used standard methodological procedures, including systematic extraction of included study characteristics and results and risk of bias assessment. Our primary outcome was reduction in gambling symptom severity. Our secondary outcomes were reduction in gambling expenditure, gambling frequency, time spent gambling, depressive symptoms, anxiety symptoms, and functional impairment; and responder status. We evaluated treatment effects for continuous and dichotomous outcomes using standardised mean difference (SMD) and risk ratios (RR), respectively, employing random-effects meta-analyses. A minimum of two independent treatment effects were required for a meta-analysis to be conducted (with only meta-analytic findings reported in this abstract).. We included 17 studies in the review (n = 1193 randomised) that reported outcome data scheduled for end of treatment. Length of treatment ranged from 7 to 96 weeks.  Antidepressants: Six studies (n = 268) evaluated antidepressants, with very low to low certainty evidence suggesting that antidepressants were no more effective than placebo at post-treatment: gambling symptom severity (SMD -0.32, 95% CI -0.74 to 0.09, n = 225), gambling expenditure (SMD -0.27, 95% CI -0.60 to 0.06, n = 144), depressive symptoms (SMD -0.19, 95% CI -0.60 to 0.23, n = 90), functional impairment (SMD -0.15, 95% CI -0.53 to 0.22, n = 110), and responder status (RR 1.24, 95% CI 0.93 to 1.66, n = 268). Opioid antagonists: Four studies (n = 562) evaluated opioid antagonists, with very low to low certainty evidence showing a medium beneficial effect of treatment on gambling symptom severity relative to placebo at post-treatment (SMD -0.46, 95% CI -0.74 to -0.19, n = 259), but no difference between groups in responder status (RR 1.65, 95% CI 0.86 to 3.14, n = 562). Mood stabilisers: Two studies (n = 71) evaluated mood stabilisers (including anticonvulsants), with very low certainty evidence suggesting that mood stabilisers were no more effective than placebo at post-treatment: gambling symptom severity (SMD -0.92, 95% CI -2.24 to 0.39, n = 71), depressive symptoms (SMD -0.15, 95% CI -1.14 to 0.83, n = 71), and anxiety symptoms (SMD -0.17, 95% CI -0.64 to 0.30, n = 71). Atypical antipsychotics:Two studies (n = 63) evaluated the atypical antipsychotic olanzapine, with very low certainty evidence showing a medium beneficial effect of treatment on gambling symptom severity relative to placebo at post-treatment (SMD -0.59, 95% CI -1.10 to -0.08, n = 63). Comparative effectiveness: Two studies (n = 62) compared antidepressants with opioid antagonists, with very low certainty evidence indicating that antidepressants were no more effective than opioid antagonists on depressive symptoms (SMD 0.22, 95% CI -0.29 to 0.72, n = 62) or anxiety symptoms (SMD 0.21, 95% CI -0.29 to 0.72, n = 62) at post-treatment. Two studies (n = 58) compared antidepressants with mood stabilisers (including anticonvulsants), with very low certainty evidence indicating that antidepressants were no more effective than mood stabilisers on depressive symptoms (SMD 0.02, 95% CI -0.53 to 0.56, n = 58) or anxiety symptoms (SMD 0.16, 95% CI -0.39 to 0.70, n = 58) at post-treatment. Tolerability and adverse events: Several com. This review provides preliminary support for the use of opioid antagonists (naltrexone, nalmefene) and atypical antipsychotics (olanzapine) to produce short-term improvements in gambling symptom severity, although a lack of available evidence precludes a conclusion regarding the degree to which these pharmacological agents can improve other gambling or psychological functioning indices. In contrast, the findings are inconclusive with regard to the effects of mood stabilisers (including anticonvulsants) in the treatment of disordered or problem gambling, and there is limited evidence to support the efficacy of antidepressants. However, these conclusions are based on very low to low certainty evidence characterised by a small number of included studies, high risk of bias, modest pooled sample sizes, imprecise estimates, moderate between-study heterogeneity, and exclusion of participants with psychiatric comorbidities. Moreover, there were insufficient studies to conduct meta-analyses on many outcome measures; to compare efficacy across and within major categories of interventions; to explore dosage effects; or to examine effects beyond post-treatment. These limitations suggest that, despite recommendations related to the administration of opioid antagonists in the treatment of disordered or problem gambling, pharmacological interventions should be administered with caution and with careful consideration of patient needs. A larger and more methodologically rigorous evidence base with longer-term evaluation periods is required before definitive conclusions can be drawn about the effectiveness and durability of pharmacological treatments for disordered or problem gambling.

Topics: Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Gambling; Headache; Humans; Naltrexone; Narcotic Antagonists; Nausea; Olanzapine

Common treatment methods for malignant tumors include surgery, chemotherapy, radiotherapy, immunotherapy, targeted therapy, etc., among which chemotherapy plays an important role. However, chemotherapy brings corresponding side effects while killing tumor cells, and nausea and vomiting are the most common adverse reactions induced by chemotherapy. It not only affects the patient's appetite, resulting in malnutrition and electrolyte disturbances, but also reduces the patient's compliance with treatment, which further aggravates the disease. Thus, it is important to quickly prevent and cure nausea and vomiting induced by chemotherapy (CINV). In addition, with the continuous development of medicine, more and more antiemetic drugs have been developed. At present, the most common antiemetic agents for chemotherapy-induced nausea and vomiting are NK-1R antagonists, 5-HT3R antagonists, and dexamethasone. Surprisingly, olanzapine, often used as a psychotropic drug, has been found to be an effective antiemetic and is similar to other regimens on the safety of medicine. However, although there are numerous studies on the antiemetic effects of olanzapine, its comprehensive application remains unclear. Therefore, this review will elaborate the antiemetic effect of olanzapine in terms of the antiemetic mechanism and the safety, economic cost, dose, administration time, and drug delivery aspects.

Topics: Antiemetics; Antineoplastic Agents; Humans; Nausea; Olanzapine; Pharmaceutical Preparations; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is a serious side effect of chemotherapy that negatively impacts the quality of life of oncological patients and is associated with the emetogenic risk specific to administered chemotherapy. Current practice guidelines on the use of antiemetics in CINV include the option of adding olanzapine to antiemetic regimens in the management of adult CINV. The use of olanzapine in pediatric CINV has been restricted to children with poor CINV control. Research on the use of olanzapine in pediatric CINV has been limited. The aim of this review was to evaluate current evidence on the effective and safe antiemetic use of olanzapine in pediatric CINV of any type following chemotherapy of any emetogenicity. Ovid MEDLINE, Embase, CENTRAL databases were searched for any literature on the use of olanzapine in pediatric CINV published from 2015 to 2022. Studies that reported on the olanzapine-containing antiemetic regimen in peadiatric CINV control specifically were included. Search restrictions were placed on research published in English. The search generated 43 records that were assessed for eligibility. Out of 10 identified eligible studies a third were RCT. Findings of this review suggest that adding olanzapine to antiemetic regimen in pediatric CINV control is a worthwhile consideration. Further research is needed to establish the efficacy and safety of antiemetic olanzapine use in pediatric CINV.

Topics: Adult; Antiemetics; Antineoplastic Agents; Child; Humans; Nausea; Olanzapine; Quality of Life; Vomiting

Olanzapine has been found to have antiemetic properties due to its ability to inhibit multiple serotonergic, dopaminergic, alpha-1 adrenergic and histamine receptors. In 2016, a meta-analysis of 10 randomized controlled trials (RCTs) on olanzapine in the prophylactic setting found olanzapine to be more efficacious than other standard antiemetics in the prophylactic setting. However, since the review, many clinical trials using olanzapine for chemotherapy-induced nausea and vomiting (CINV) have been published-in many cases, contending that further trials would further help elucidate the efficacy of olanzapine for CINV given the continued paucity of literature. The primary aim of this study is to conduct a secondary, cumulative meta-analysis to assess the impact of the most recent trials on the published effect estimate of olanzapine and ultimately determine whether trials published since 2016 have significantly changed the summary estimate.. As reported previously, a literature search was conducted up until 2015, of Ovid Medline, Embase and the Cochrane Central Register of Controlled Trials; 10 RCTs with a total of over 1,000 patients were included, that compared olanzapine to other antiemetics in the prophylactic setting, which reported on at least one of two endpoints-no emesis and no nausea. The Mantel-Haenszel, random-effects analysis model was used to compute cumulative risk ratios (RR) and their accompanying 95% confidence intervals (CIs).. For the endpoint of emetic control, the cumulative meta-analysis shows that the summary effect did not change noticeably with the inclusion of the most recent trials. In the acute phase, the RR shifted from 1.07 before 2011 to 1.10 after 2015, even after the inclusion of 7 trials. Similar small changes were noted in the delayed and overall phases. For the endpoint of nausea control, the cumulative meta-analysis does show a significant visual change in summary effect, except for nausea control in the acute phase. In the delayed phase, the RR shifts from 1.58 before 2011 to 1.50 after 2015. In the overall phase, the RR shifts from 1.642 before 2011 to 1.53 after 2015.. Olanzapine's efficacy for the prophylaxis of CINV has been sufficiently documented, with respect to emetic control. There is, however, more limited data supporting its efficacy with respect to nausea control.

Topics: Antiemetics; Antineoplastic Agents; Humans; Nausea; Olanzapine; Vomiting

The aim of this study is to rigorously review the efficacy and safety of olanzapine in defined hematology oncology settings including (1) the setting of highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC) settings (2) at 5 mg and 10 mg doses, and (3) for response rates for use in the acute, delayed, and overall settings post-MEC and HEC.. Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched through April 23, 2020. The primary efficacy endpoints were the rate of complete response, in the acute (0-24 h post-chemotherapy), delayed (24-120 h post-chemotherapy), and overall (0-120 h post-chemotherapy) phases. The secondary efficacy endpoints were the rates of no nausea and no emesis, for each phase. Safety endpoints were the rate of no serious adverse events (i.e., no grade 3 or 4 toxicities), as assessed by Common Terminology Criteria for Adverse Events (CTCAE) criteria. The Mantel-Haenszel, random-effects analysis model was used to compute risk ratios and accompanying 95% confidence intervals for each endpoint. For endpoints that statistically favored one arm, absolute risk differences were computed to assess whether there is a 10% or greater difference, used as the threshold for clinical significance by MASCC/ESMO. Fragility indices were also calculated for each statistically significant endpoint, to quantitatively assess the robustness of the summary estimate. A cumulative meta-analysis was conducted for each efficacy meta-analysis with more than 5 studies, also using the Mantel-Haenszel random-effects analysis model.. Three studies reported on olanzapine for the rescue of breakthrough chemotherapy-induced nausea and vomiting (CINV); 22 studies reported on olanzapine in the prophylactic setting. For studies reporting on HEC patients, olanzapine-containing regimens were statistically and clinically superior in seven of nine efficacy endpoints in the prophylaxis setting. When olanzapine is administered at a 10-mg dose, it is statistically and clinically superior to control patients in eight of nine endpoints among adults. Olanzapine may be effective in the MEC setting and when administered at 5-mg doses, but the paucity of data leads to notable uncertainty.. Further RCTs are needed in the setting of MEC patients and administration of olanzapine at a lower 5-mg dose, which may be given to reduce the sedative effect of olanzapine at 10 mg.

Topics: Adolescent; Adult; Aged; Antiemetics; Antineoplastic Agents; Humans; Middle Aged; Nausea; Olanzapine; Vomiting; Young Adult

Olanzapine, neurokinin-1-receptor-antagonists (NK-1-RA), and thalidomide added to palonosetron + dexamethasone (PALO-DEX) have been evaluated in separate studies as prophylaxis for chemotherapy-induced nausea and vomiting (CINV) due to highly emetogenic chemotherapy (HEC). We conducted a Bayesian network meta-analysis to compare the prophylactic efficacy of these agents in combination with PALO-DEX.. PubMed, Medline/Ovid, Embase, and Clinicaltrials.gov were searched from inception through 22 Mar 2018. Study quality was assessed using the Cochrane methodology. A Bayesian network meta-analysis using random-effects models was used to asses complete response (CR) and rate of no nausea (RNN) in acute, delayed, and overall phases and were expressed as odds ratios (OR) and 95% credible interval (95% CrI). Ranking probabilities of treatments were calculated using the surface under the cumulative ranking curve (SUCRA) to identify the probability of a given treatment as the best option against the worst option.. Nine RCTs involving two thousand nine hundred fifty-nine patients were included. The olanzapine-based regimen showed greater CR in the acute, delayed, and overall-phases versus the PALO-DEX regimen (OR = 3.97, 95% CrI = 1.02-19.13; OR = 5.62, 95% CrI = 1.66-28.58; OR = 4.79, 95% CrI = 1.40-24.02, respectively). Additionally, it showed greater RNN than the NK-1-RA-based and the PALO-DEX regimens in the delayed phase only (OR = 2.90, 95% CrI = 1.34-5.15; OR = 4.53, 95% CrI = 1.89-10.55, respectively). Olanzapine-, NK-1-RA-, and thalidomide-based regimens did not differ in CR in the three phases. SUCRA probabilities ranked the olanzapine-based regimen as the best option in terms of CR and RNN, while ranking the NK-1-RA-based regimens as the second best option in terms of CR throughout the three phases.. Based on the data included in the analyses, there is insufficient evidence to support adding thalidomide or NK-1-RA to PALO-DEX in preventing CINV induced by HEC. However, adding olanzapine to PALO-DEX achieves better CR and RNN. Olanzapine side-effects and the absence of direct comparisons explain why some guidelines are cautious in suggesting the use of olanzapine.

Topics: Antiemetics; Antineoplastic Agents; Bayes Theorem; Dexamethasone; Drug Therapy, Combination; Humans; Induction Chemotherapy; Nausea; Network Meta-Analysis; Neurokinin-1 Receptor Antagonists; Olanzapine; Palonosetron; Randomized Controlled Trials as Topic; Thalidomide; Vomiting

We performed a pooled analysis to evaluate the efficacy and adverse events (AEs) of olanzapine combined with dexamethasone plus 5-hydroxytryptamine type 3 receptor antagonist (5-HT3 RA) compared with 5-HT3 RA plus dexamethasone for the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) in high and moderate emetogenic chemotherapy based on randomised controlled trials (RCTs). PubMed, EMBASE, Web of Science, the Cochrane Library, China Biomedical Literature database (CBM), WanFang Database, China National Knowledge Infrastructure (CNKI), and Chinese Science and Technology Periodical Database (VIP) (from their inception to April 2019) were searched to capture relevant articles. Relative risk with 95% confidence intervals for CINV and AEs were all extracted or calculated. Eleven studies with 1107 cancer patients were involved in this review. The pooled RR of delayed CINV (RR 0.50, 95% CI 0.38 to 0.66; p<0.01) were significantly decreased in the olanzapine group. The occurrence of insomnia was also statistically decreased, as was the rate of acute CINV (RR 0.60, 95% CI 0.48 to 0.75; p<0.01). However, only the percentages of CINV III and CINV IV were significantly decreased in the acute and delayed phases. Subgroup analysis demonstrated that the efficacy was not statistically significantly different between 5 mg and 10 mg olanzapine. Olanzapine significantly decreased the occurrence of CINV III and IV and insomnia in high and moderately emetogenic chemotherapy. Compared with 10 mg per day, 5 mg oral olanzapine may be more appropriate for patients with cancer.

Topics: Antiemetics; Antineoplastic Agents; Dexamethasone; Humans; Nausea; Olanzapine; Randomized Controlled Trials as Topic; Serotonin 5-HT3 Receptor Antagonists; Vomiting

Olanzapine is an atypical antipsychotic that has affinity for many central nervous system receptors. Its efficacy is supported by several studies in the prevention and treatment of chemotherapy-induced nausea and vomiting. No recommendations exist on the antiemetic use of olanzapine in the palliative care setting. The aim of this work is to complete the initial work of Fonte et al. published in 2015, to determine whether the literature supports the use of olanzapine as an antiemetic in palliative situations and, in practice, to propose a therapeutic schema adapted to the palliative setting.. Systematic review of the literature according to the PRISMA criteria. We searched the PubMed, Cochrane, RefDoc, EMBase databases and the gray literature databases. The bibliographic search was conducted between November 2016 and August 2017.. Thirteen articles were included: 2 case studies, 3 case series, 3 retrospective studies, 2 prospective studies, 2 literature reviews. All studies concluded on the efficacy of olanzapine as an antiemetic in the palliative care setting. No serious adverse effects were reported. Based on the data from the literature review, we propose a therapeutic scheme adapted to the palliative care context.. Action of olanzapine on many receptors and its tolerance profile make it an interesting antiemetic treatment in palliative medicine. But to date, studies are scarce and have a low statistical power. Further investigation is therefore needed to determine the benefit of this treatment in palliative care patients, compared to usual treatments.

Topics: Antiemetics; Antipsychotic Agents; Humans; Nausea; Olanzapine; Palliative Medicine; Vomiting

Olanzapine has become a major drug in the management of chemotherapy-induced nausea and vomiting as a prophylactic agent. In addition, a recent randomized trial has demonstrated its benefits in treating nausea and vomiting associated with advanced cancer. The added benefit to olanzapine is that it also stimulates appetite. As a result, since it treats multiple symptoms associated with advanced cancer, it is likely to become the antiemetic of choice in palliative care at least in the USA. The added benefit of treating insomnia and the avoidance of benzodiazepines should place olanzapine in at the top of the list of drugs to use for patients who do complain of insomnia. There is no good evidence that it potentiates the respiratory depression of opioids unlike benzodiazepines. The evidence is weak that olanzapine in as an adjuvant analgesic. Hopefully, future trials will explore this in greater depth. The benefits of adding olanzapine to potent opioids are that it may reduce craving, drug cues, and opioid misuse. Other symptoms like anxiety and depression may be addressed by the addition of olanzapine to standard antidepressants.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Antipsychotic Agents; Drug Monitoring; Humans; Nausea; Neoplasms; Olanzapine; Palliative Care; Postoperative Complications; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Vomiting

It is important to control chemotherapy-induced nausea and vomiting (CINV) to maintain dose intensity and patients' quality of life. The National Comprehensive Cancer Network guidelines suggest combination therapy of antiemetic agents. The growing number of antiemetic regimens, and in particular the growing use of regimens containing antagonists to the Nk-1 receptor (NK1RAs) and the antipsychotic drug olanzapine (OLZ), call for the re-evaluation of the optimal regimen for CINV. This study assessed the efficacy and safety of antiemetic regimens for highly emetogenic chemotherapy, using Bayesian network meta-analysis.. Randomized trials that compared different antiemetic regimens were included. We strictly followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The main outcomes were the odds ratio (OR) for overall complete response (absence of vomiting). We conducted network meta-analysis within a Bayesian model to combine the direct and indirect evidence. Safety was assessed from the trial description. All statistical tests were two-sided.. We systematically reviewed 27 randomized control trials (13,356 participants), which compared 12 different antiemetic regimens: serotonin-3 receptor antagonist (5HT3), 5HT3 + dexamethasone (Dex), palonosetron (PAL), PAL + Dex, PAL at 0.75 mg (PAL0.75), PAL0.75 + Dex, NK1RA + 5HT3 + Dex, NK1RA + PAL + Dex, an oral combination of netupitant and palonosetron (NEPA) + Dex, OLZ + 5HT3 + Dex, OLZ + PAL + Dex, and OLZ + NK1RA + 5HT3 + Dex. An NK1RA + 5HT3 + Dex regimen and an NK1RA + palonosetron + Dex regimen gave a higher complete response (CR) rate than the reference regimen, 5HT3 + Dex (OR, 1.75; 95% credibility interval [95% CrI], 1.56-1.97, and OR, 2.25; 95% CrI, 1.66-3.03, respectively). A regimen containing NEPA was more effective in producing CR than conventional regimens without NEPA or olanzapine. Further analysis, based on the surface under the cumulative ranking probability curve, indicated that olanzapine-containing regimens were the most effective in producing CR.. Our meta-analysis supports the conclusion that olanzapine-containing regimens are the most effective for CINV of highly emetogenic chemotherapy. We confirmed that NK1RA + PAL + Dex is the most effective of conventional regimens. Substituting olanzapine for an Nk-1 receptor antagonist may offer a less costly and more effective alternative for patients.. Nausea and vomiting during chemotherapy often pose difficulties for patients and doctors, making it hard to continue the proper therapy and to maintain the quality of life. This article gives insights into the optimal choice of medicine to treat nausea during chemotherapy. The findings reported here provide readers with a robust efficacy ranking of antinausea medicine, which can be used as a reference for the best possible treatment. Furthermore, the 70% less costly drug, olanzapine, is suggested to be equally effective to aprepitant in reducing nausea and vomiting. The possibility of offering a cost-effective treatment to a wider range of the population is discussed.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cost-Benefit Analysis; Drug Costs; Humans; Nausea; Neoplasms; Network Meta-Analysis; Olanzapine; Practice Guidelines as Topic; Quality of Life; Randomized Controlled Trials as Topic; Vomiting

The current antiemetic prophylaxis for patients treated with highly emetogenic chemotherapy (HEC) included the olanzapine-based triplet and neurokinin-1 receptor antagonists (NK-1RAs)-based triplet. However, which one shows better antiemetic effect remained unclear.. We systematically reviewed 43 trials, involving 16,609 patients with HEC, which compared the following antiemetics at therapeutic dose range for the treatment of chemotherapy-induced nausea and vomiting: olanzapine, aprepitant, casopitant, fosaprepitant, netupitant, and rolapitant. The main outcomes were the proportion of patients who achieved no nausea, complete response (CR), and drug-related adverse events. A Bayesian network meta-analysis was performed.. Olanzapine-based triple regimens showed significantly better no-nausea rate in overall phase and delayed phase than aprepitant-based triplet (odds ratios 3.18, 3.00, respectively), casopitant-based triplet (3.78, 4.12, respectively), fosaprepitant-based triplet (3.08, 4.10, respectively), rolapitant-based triplet (3.45, 3.20, respectively), and conventional duplex regimens (4.66, 4.38, respectively). CRs of olanzapine-based triplet were roughly equal to different NK-1RAs-based triplet but better than the conventional duplet. Moreover, no significant drug-related adverse events were observed in olanzapine-based triple regimens when compared with NK-1RAs-based triple regimens and duplex regimens. Additionally, the costs of olanzapine-based regimens were obviously much lower than the NK-1RA-based regimens.. Olanzapine-based triplet stood out in terms of nausea control and drug price but represented no significant difference of CRs in comparison with NK-1RAs-based triplet. Olanzapine-based triple regimens should be an optional antiemetic choice for patients with HEC, especially those suffering from delayed phase nausea.. According to the results of this study, olanzapine-based triple antiemetic regimens were superior in both overall and delayed-phase nausea control when compared with various neurokinin-1 receptor antagonists-based triple regimens in patients with highly emetogenic chemotherapy (HEC). Olanzapine-based triplet was outstanding in terms of nausea control and drug price. For cancer patients with HEC, especially those suffering from delayed-phase nausea, olanzapine-based triple regimens should be an optional antiemetic choice.

Topics: Humans; Nausea; Network Meta-Analysis; Neurokinin-1 Receptor Antagonists; Olanzapine; Vomiting

Olanzapine as an antiemetic represents a new use of an antipsychotic drug. People with cancer may experience nausea and vomiting whilst receiving chemotherapy or radiotherapy, or whilst in the palliative phase of illness.. To assess the efficacy and safety of olanzapine when used as an antiemetic in the prevention and treatment of nausea and vomiting related to cancer in adults.. We searched CENTRAL, MEDLINE and Embase for published data on 20th September 2017, as well as ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform for unpublished trials. We checked reference lists, and contacted experts in the field and study authors.. We included randomised controlled trials (RCTs) of olanzapine versus any comparator with or without adjunct therapies for the prevention or treatment, or both, of nausea or vomiting in people with cancer aged 18 years or older, in any setting, of any duration, with at least 10 participants per treatment arm.. We used standard Cochrane methodology. We used GRADE to assess quality of evidence for each main outcome. We extracted data for absence of nausea or vomiting and frequency of serious adverse events as primary outcomes. We extracted data for patient perception of treatment, other adverse events, somnolence and fatigue, attrition, nausea or vomiting severity, breakthrough nausea and vomiting, rescue antiemetic use, and nausea and vomiting as secondary outcomes at specified time points.. We included 14 RCTs (1917 participants) from high-, middle- and low-income countries, representing over 24 different cancers. Thirteen studies were in chemotherapy-induced nausea and vomiting. Oral olanzapine was administered during highly emetogenic (HEC) or moderately emetogenic (MEC) chemotherapy (12 studies); chemoradiotherapy (one study); or palliation (one study). Eight studies await classification and 13 are ongoing.The main comparison was olanzapine versus placebo/no treatment. Other comparisons were olanzapine versus NK1 antagonist, prokinetic, 5-HT3 antagonist or dexamethasone.We assessed all but one study as having one or more domains that were at high risk of bias. Eight RCTs with fewer than 50 participants per treatment arm, and 10 RCTs with issues related to blinding, were at high risk of bias. We downgraded GRADE assessments due to imprecision, inconsistency and study limitations.Olanzapine versus placebo/no treatmentPrimary outcomesOlanzapine probably doubles the likelihood of no nausea or vomiting during chemotherapy from 25% to 50% (risk ratio (RR) 1.98, 95% confidence interval (CI) 1.59 to 2.47; 561 participants; 3 studies; solid tumours; HEC or MEC therapy; moderate-quality evidence) when added to standard therapy. Number needed to treat for additional beneficial outcome (NNTB) was 5 (95% CI 3.3 - 6.6).It is uncertain if olanzapine increases the risk of serious adverse events (absolute risk difference 0.7% more, 95% CI 0.2 to 5.2) (RR 2.46, 95% CI 0.48 to 12.55; 7 studies, 889 participants, low-quality evidence).Secondary outcomesFour studies reported patient perception of treatment. One study (48 participants) reported no difference in patient preference. Four reported quality of life but data were insufficient for meta-analysis.Olanzapine may increase other adverse events (RR 1.71, 95% CI 0.99 to 2.96; 332 participants; 4 studies; low-quality evidence) and probably increases somnolence and fatigue compared to no treatment or placebo (RR 2.33, 95% CI 1.30 to 4.18; anticipated absolute risk 8.2% more, 95% CI 1.9 to 18.8; 464 participants; 5 studies; moderate-quality evidence). Olanzapine probably does not affect all-cause attrition (RR 0.99, 95% CI 0.57 to 1.73; 943 participants; 8 studies; I² = 0%). We are uncertain if olanzapine increases attrition due to adverse events (RR 3.00, 95% CI 0.13 to 70.16; 422 participants; 6 studies). No participants withdrew due to lack of efficacy.We are uncertain if olanzapine reduces breakthrough nau. There is moderate-quality evidence that oral olanzapine probably increases the likelihood of not being nauseous or vomiting during chemotherapy from 25% to 50% in adults with solid tumours, in addition to standard therapy, compared to placebo or no treatment. There is uncertainty whether it increases serious adverse events. It may increase the likelihood of other adverse events, probably increasing somnolence and fatigue. There is uncertainty about relative benefits and harms of 5 mg versus 10 mg.We identified only RCTs describing oral administration. The findings of this review cannot be extrapolated to provide evidence about the efficacy and safety of any injectable form (intravenous, intramuscular or subcutaneous) of olanzapine.

Topics: Adult; Antiemetics; Antineoplastic Agents; Benzodiazepines; Chemoradiotherapy; Dexamethasone; Disorders of Excessive Somnolence; Fatigue; Humans; Metoclopramide; Nausea; Neoplasms; Olanzapine; Quality of Life; Randomized Controlled Trials as Topic; Vomiting

Olanzapine is an anti-psychotic drug that has been used for preventing and treating Chemotherapy-Induced Nausea and Vomiting (CINV). This study aimed to systematically review and meta-analyze the efficacy and safety of olanzapine for prophylaxis and treatment of CINV.. We conducted a systematic literature search of MEDLINE, EMBASE, SCOPUS, and the Cochrane Central Register of Controlled Trials-CENTRAL up to July 15, 2016. All observational and intervention studies were included, but only the intervention studies were pooled for meta-analysis. The efficacy outcome was the proportion of patients achieving complete response (CR) - no emesis and no rescue therapy, in the acute, delayed, and overall phases. The safety outcomes were the adverse events associated with olanzapine according to Common Terminology Criteria for Adverse Events (CTCAE).. Sixteen studies were eligible: 15 clinical trials and 1 observational study. Nine of the interventional studies were pooled for meta-analysis. The CR of olanzapine was superior to other anti-emetic regimens, in both the delayed and overall phases (RR=1.27, 95% CI 1.07-1.49, RR=1.32, 95% CI 1.08-1.62, respectively). However, olanzapine was not better than standard CINV prophylaxis of the nausea and emesis outcome in the acute phase. Drowsiness and constipation were the most reported adverse events. No grade 3 or 4 adverse events were reported.. Olanzapine is effective and safe at reducing during the delayed and overall phase of the CINV prevention. Other regimens might be added, in cases of CINV during the acute phase of CINV.

Topics: Antiemetics; Antineoplastic Agents; Benzodiazepines; Humans; Nausea; Olanzapine; Vomiting

An expanding array of options for prevention and treatment of chemotherapy-induced nausea and vomiting (CINV), including regimens containing olanzapine or recently approved neurokinin 1 (NK. Up to 80% of patients receiving chemotherapy have CINV. Current practice guidelines recommend that patients treated with highly emetogenic chemotherapy also receive a 3-drug antiemetic regimen initiated on the day of and continued for 3 days after chemotherapy administration, with the most commonly used 3-drug regimen consisting of an NK. Newer therapeutic options for the management of CINV are equivalent to standard-of-care regimens in terms of efficacy and toxicity. While the NK

Topics: Antiemetics; Humans; Nausea; Neurokinin-1 Receptor Antagonists; Olanzapine; Serotonin Antagonists; Vomiting

Nausea and vomiting are frequent and fearful issues both of cancer itself and its treatment, resulting in reduced quality of life, hospitalization and unnecessary medical investigations. Unconventionally, the author discusses the treatment-related and non-treatment-related complaints together, so as to give an integrated approach to this problem. Different types of nausea/vomiting and important causes are explained by discussion of the pathophysiology and clinical symptoms. Different classes of antiemetics are detailed, emphasizing the evolving role of olanzapine in the treatment of both the acute and delayed type of chemotherapy-induced nausea/vomiting. It was no aim of this review to detail all aspects of MASCC and ESMO antiemetic guideline issued in 2016, but the main topics are presented together with other antiemetic strategies.. Mind a daganatos betegségnek, mind az onkológiai kezelésnek gyakori, rettegett velejárója a hányinger, ill. a hányás, mely jelentõsen rontja az életminõséget, hospitalizációt és felesleges vizsgálatokat eredményezhet. A szerzõ – rendhagyó módon – együtt tárgyalja a kemo- és sugárterápiához társuló, valamint a betegség elõrehaladott stádiumában jelentkezõ ezen panaszokat, egységes szemléletet kívánva adni a probléma kezeléséhez. A patofiziológiai alapok áttekintése kapcsán bemutatja a hányinger-hányás különbözõ típusait, gyakorlati szempontokat szem elõtt tartó differenciáldiagnosztikáját, majd részletesen bemutatja a különbözõ hányáscsillapító gyógyszercsoportokat. Kiemeli az elmúlt néhány év vizsgálati eredményei alapján az olanzapin meglepõen jó hatékonyságát mind a kemoterápiához társuló akut, mind a késõi típusú hányinger-hányás megelõzésében, ill. kezelésében. Bár nem törekszik a MASCC és ESMO által 2016-ban kibocsátott új antiemetikus vezérelv teljes körû ismertetésére, ennek összefoglaló ajánlása az egyéb eredetû hányinger-hányás csillapítással együtt bemutatásra kerül.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Diagnosis, Differential; Humans; Hungary; Nausea; Neoplasms; Olanzapine; Palliative Care; Prognosis; Risk Assessment; Severity of Illness Index; Treatment Outcome; Vomiting

The aim of the present study was to evaluate the efficacy of olanzapine for the prevention of chemotherapy-induced nausea and vomiting (CINV).. The literature was searched for randomized controlled trials (RCTs) evaluating the efficacy of olanzapine for the prophylaxis of CINV using PubMed, Embase, Central, as well as clinicaltrials.gov for unpublished studies. The endpoints of the study were the number of patients who achieved a complete response (CR; no emesis and no rescue) and no nausea in the acute, delayed and overall phases. Two authors independently selected studies, assessed the risk of bias and extracted data. The included RCTs were analysed using RevMan 5.3 provided by the Cochrane Collaboration.. Ten RCTs were identified for the meta-analysis. Compared with other antiemetic agents, olanzapine significantly improved the CR in the delayed and overall phases, but did not enhance the CR in the acute phase. For the control of CINV, olanzapine was better than and comparable with aprepitant in the acute phase and delayed phase, respectively. Compared with placebo, treatment with 5 mg and 10 mg olanzapine exhibited similar efficacy in terms of the CR in the delayed and overall phases.. Olanzapine is an excellent alternative for the prophylaxis of CINV. Olanzapine 5 mg per day should be recommended as the initial dose because of equivalent efficacy to a 10 mg dose but a lower potential risk of side effects. Further studies are needed to explore the optimal combination of medicines.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Humans; Morpholines; Nausea; Neoplasms; Olanzapine; Randomized Controlled Trials as Topic; Treatment Outcome; Vomiting

Olanzapine is an atypical antipsychotic drug that inhibits serotonergic, dopaminergic, alpha-1 adrenergic, histaminic, and muscarinic receptors. Several phase I and II trials have been published documenting the use of olanzapine in controlling chemotherapy-induced nausea and vomiting (CINV). This review aims to summarize all phase I and II trials that reported on olanzapine for the prophylaxis of CINV.. A literature search was conducted in Ovid MEDLINE from 1946 to July week 1 2015, Embase Classic and Embase from 1947 to 2015 week 28, and the Cochrane Central Register of Controlled Trials up until June 2015. Phase I and II trials reporting on olanzapine for the prophylaxis for CINV were included if they reported on at least one of four primary endpoints: complete response (CR), complete control (CC), no nausea, and no emesis. Other endpoints of interest included the safety of olanzapine as measured by the M.D. Anderson Symptom Inventory.. Across the seven included studies, there were a total of 201 patients. The CR across four studies was 97.2, 83.1, and 82.8 % for the acute, delayed, and overall phases, respectively. The CC for acute, delayed, and overall phases was 92.5, 87.5, and 82.5 %, respectively. The overall no nausea rate was 92.7, 71.8, and 70.6 % for the acute, delayed, and overall phases, respectively. The overall no emesis rates for the acute, delayed, and overall phases were 100, 94.5, and 90.4 %, respectively. Fatigue, drowsiness, and disturbed sleep were common side effects.. Olanzapine is efficacious and safe when used as a prophylaxis for CINV.

Topics: Antiemetics; Antineoplastic Agents; Antipsychotic Agents; Benzodiazepines; Dyssomnias; Fatigue; Humans; Induction Chemotherapy; Male; Middle Aged; Nausea; Olanzapine; Remission Induction; Sleep Wake Disorders; Vomiting

Olanzapine is a potent antipsychotic medication that inhibits a wide variety of receptors. It has been used in trials for the prophylaxis and rescue of chemotherapy-induced nausea and vomiting (CINV). This study systematically investigates the efficacy of olanzapine in relation to other antiemetics in the prophylaxis and rescue of CINV.. A literature search of Ovid MEDLINE, EMBASE, and CENTRAL was conducted to identify randomized controlled trials (RCTs) comparing olanzapine to other standard antiemetics for either prevention or rescue. The primary endpoints were the percentage of patients achieving no emesis or no nausea, in the acute, delayed, and overall phases.. Ten RCTs in the preventative setting and three RCTs in the breakthrough setting were identified. Subgroup analysis demonstrated a similar degree of benefit from a 5- and 10-mg dose of olanzapine for the no emesis endpoint in the overall phase. In the prophylaxis setting, olanzapine was statistically superior in five of six endpoints and clinically superior in four of six endpoints. In the breakthrough setting, olanzapine was statistically and clinically superior in the only endpoint analyzed: no emesis.. Olanzapine is more efficacious than other standard antiemetics for the rescue of CINV and its inclusion improves control in the prevention setting. Given the possible reduction in side effects, the use of a 5-mg dose of olanzapine should be considered. Future RCTs should compare the 5-mg versus the 10-mg dosages further and report on the efficacy and percentage of patients developing side effects. Further analyses should be done without the influence of corticosteroids.

Topics: Antiemetics; Antineoplastic Agents; Benzodiazepines; Female; Humans; Induction Chemotherapy; Nausea; Olanzapine; Vomiting

The prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) continues to pose a challenge for clinicians. The development of 5-hydroxytryptamine (serotonin) antagonists and neurokinin-1 receptor antagonists (NK1 -RAs) have demonstrated significant improvements in acute and delayed CINV for highly and moderately emetogenic chemotherapy. Delayed and breakthrough CINV, however, continue to be difficult to manage despite available treatment agents. Randomized clinical trial data suggest that olanzapine, a second-generation thienobenzodiazepine, traditionally used in the treatment of manifestations of psychotic disorders, is an effective agent in these clinical settings. The short-term use of olanzapine has a favorable adverse event profile and was not associated with grade 3 or 4 toxicity in a phase III study. Olanzapine is recommended as an option within first-line prophylaxis for CINV in the National Comprehensive Cancer Network (NCCN) guidelines and is an option for treatment of refractory CINV in the Multinational Association of Supportive Care in Cancer/European Society for Medical Oncology and NCCN guidelines.

Topics: Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Benzodiazepines; Cancer Care Facilities; Evidence-Based Medicine; Humans; International Agencies; Nausea; Olanzapine; Practice Guidelines as Topic; Selective Serotonin Reuptake Inhibitors; Serotonin Antagonists; Societies, Hospital; Societies, Medical; Vomiting

The purpose of review is to critically present the evidence supporting the use of olanzapine, an atypical antipsychotic, as an antiemetic for cancer and chemotherapy-induced nausea and vomiting (CINV).. Two phase III clinical studies demonstrated superior efficacy of olanzapine in comparison with the neurokinin-1 receptor antagonists (NK1RA) for substance P (aprepitant, fosaprepitant) in the prevention of nausea after highly emetogenic chemotherapy. Olanzapine is inexpensive and the replacement of NK1RA with olanzapine can reduce the costs of the prevention of CINV. The addition of olanzapine to aprepitant-containing combination regimens for the prevention of CINV was also investigated, and has the potential to further improve the prevention of CINV after highly emetogenic chemotherapy or moderately emetogenic chemotherapy, without substantial increase in costs. In the treatment of uncontrolled ('breakthrough') CINV, olanzapine was more effective than metoclopramide. Existing clinical data also support the use of olanzapine to relieve a cluster of gastrointestinal symptoms in patients with advanced cancer (chronic nausea, vomiting, and anorexia). When used in cancer patients, olanzapine is well tolerated, with sedation being the major dose-limiting side effect.. Existing data from clinical trials justify further research of the role of olanzapine in the prevention of CINV. Olanzapine may be used instead of or in addition to NK1RA in the preventive antiemetic regimens. Olanzapine-containing preventive regimens may provide better nausea control after chemotherapy. When used instead of NK1RA it may also provide substantial reduction in costs of CINV prevention. In patients with advanced cancer, olanzapine was effective against a cluster of gastrointestinal symptoms (nausea, vomiting, and anorexia). The use of olanzapine as an antiemetic for CINV, or to relieve nausea, vomiting, and anorexia in palliative care is currently off-label.

Topics: Antiemetics; Antineoplastic Agents; Benzodiazepines; Clinical Trials, Phase III as Topic; Drug Therapy, Combination; Humans; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Olanzapine; Substance P; Vomiting

Olanzapine is an atypical antipsychotic agent that blocks multiple neuronal receptors involved in the nausea and vomiting pathways. It has therefore been studied for the prevention and treatment of chemotherapy-induced emesis and in patients in palliative care presenting nausea and vomiting refractory to standard antiemetics. Some studies have shown that olanzapine was not inferior to aprepitant in the prophylaxis of highly and moderately emetogenic chemotherapy and that it increased the rate of complete response when added to a combination of a 5-HT3 antagonist, aprepitant and dexamethasone. These studies present so many shortcomings, however, that they do not permit us to draw any firm conclusions. Oral olanzapine showed superior antiemetic efficacy to metoclopramide as rescue treatment to control breakthrough emesis induced by chemotherapy. However, an oral formulation is not appropriate because in patients with vomiting or severe nausea the mere ingestion of an oral drug could induce emesis. Finally, in palliative care olanzapine could control or reduce the intensity of nausea and vomiting refractory to standard antiemetics.

Topics: Antiemetics; Benzodiazepines; Humans; Nausea; Olanzapine; Palliative Care; Vomiting

The role of olanzapine in chemotherapy-induced nausea and vomiting (CINV) is supported from randomized controlled trials and national consensus guidelines such as the National Comprehensive Cancer Network. In contrast, the role of olanzapine in refractory non-CINV is limited to case reports/series, retrospective studies, one pilot study, and one randomized controlled trial in patients with major depressive disorder. We present a case of a 36-year-old man with dyskeratosis congenita and refractory non-CINV over several years in which low-dose olanzapine was effective and tolerable. We aim to contribute to the growing evidence supporting the use of olanzapine for refractory non-CINV. Furthermore, we review and summarize the literature regarding olanzapine in the CINV and non-CINV settings.

Topics: Adult; Antiemetics; Benzodiazepines; Humans; Male; Nausea; Olanzapine; Palliative Care; Vomiting

This review provides background information on chemotherapy-induced nausea and vomiting (CINV) classification and pathophysiology and reviews various antiemetic agents for CINV prophylaxis, including corticosteroids, serotonin receptor antagonists (5-HT3 RAs), tachykinin NK1 receptor antagonists (NK1 RAs), and olanzapine. Other less commonly used agents are briefly discussed. Practical considerations are reviewed as well, including emetogenicity of chemotherapeutic regimens, patient-specific risk factors for CINV, principles of CINV management, health economics outcome research, and quality of life. Available data on the newly FDA-approved antiemetic combination netupitant/palonosetron (NEPA) is also reviewed. Prevention of CINV is an important goal in managing patients with cancer and is especially difficult with respect to nausea and delayed CINV. Corticosteroids are a mainstay of CINV prophylaxis and are usually given in combination with other therapies. The 5-HT3 RA palonosetron has shown increased efficacy over other agents in the same class for prevention of delayed emesis with moderately emetogenic chemotherapy and NK1 RAs improve emesis prevention in combination with 5-HT3 RAs and dexamethasone. Olanzapine has shown efficacy for CINV prophylaxis and the treatment of breakthrough CINV. The new combination therapy, NEPA, has been shown to be efficacious for the prevention of acute, delayed, and overall CINV. Risk factors that have been identified for CINV include gender, age, and alcohol intake. It is important to assess the emetogenicity of chemotherapy regimens as well as the potential impact of patient risk factors in order to provide adequate prophylaxis. Acute and delayed CINV are severe, burdensome side effects of chemotherapy; however, new data on prevention and the discovery of new agents can further improve CINV control.

Topics: Adrenal Cortex Hormones; Antiemetics; Antineoplastic Agents; Benzodiazepines; Drug Combinations; Drug Therapy, Combination; Humans; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Olanzapine; Quality of Life; Risk Factors; Serotonin Antagonists; Vomiting

Olanzapine is an atypical antipsychotic agent of the thiobenzodiazepine class. It blocks multiple neurotransmitter receptors including dopaminergic at D1, D2, D3, D4 brain receptors, serotonergic at 5-HT2a, 5-HT2c, 5-HT3, 5-HT6 receptors, catecholamines at alpha1 adrenergic receptors, acetylcholine at muscarinic receptors, and histamine at H1 receptors. Olanzapine has five times the affinity for 5-HT2 receptors than D2 receptors and has been used to treat schizophrenia and delirium. Olanzapine's activity at multiple receptors, particularly at the D2, 5-HT2c, and 5-HT3 receptors which appear to be involved in nausea and emesis, has prompted its use in the treatment of nausea and vomiting refractory to standard antiemetics. Case reports and formal clinical trials have demonstrated its efficacy in the treatment of chronic nausea, the prevention of chemotherapy-induced nausea and emesis, and the treatment of breakthrough chemotherapy-induced nausea and emesis. Phase II and phase III clinical trials have demonstrated that there is a significant improvement in nausea when olanzapine is added to guideline directed prophylactic antiemetic agents 5-HT3 receptor antagonists and tachykinin NK1 receptor antagonists in patients receiving moderately or highly emetogenic chemotherapy Common side effects of olanzapine when used over a period of months include weight gain as well as an association with the onset of diabetes mellitus, but these effects have not been seen with short term use of daily doses of less than one week.

Topics: Animals; Benzodiazepines; Chronic Disease; Drug-Related Side Effects and Adverse Reactions; Humans; Nausea; Olanzapine; Vomiting

Newer drugs incorporated in prophylactic regimens for chemotherapy-induced nausea and vomiting (CINV) have resulted in significantly reduced rates of this feared complication of cytotoxic chemotherapy. However, both delayed chemotherapy-induced nausea and breakthrough CINV remain difficult areas of management and require novel treatment strategies. Recent randomized trial evidence has suggested that olanzapine, an atypical antipsychotic, may have a role in both the prevention and treatment of CINV. A systematic review was conducted to assess the efficacy of olanzapine in (a) preventing CINV in highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC) and (b) the treatment of breakthrough CINV. The toxicity of olanzapine in this setting was also reviewed.. MEDLINE, Embase and Cochrane Database of Systematic Reviews databases were searched to identify all randomized clinical trials (RCTs) investigating olanzapine in patients receiving chemotherapy.. A total of 488 patients from three trials of CINV prophylaxis and 323 patients from three trials of breakthrough CINV were included. Regimens including olanzapine were associated with significant improvements in CINV prevention with both HEC and MEC. Single agent olanzapine for breakthrough nausea was superior to standard alternative options.. Data from RCTs support the use of an olanzapine containing combination regimen as an option for CINV prophylaxis and single agent olanzapine for the treatment of breakthrough CINV. In the included trials, the short duration of olanzapine appears safe and well tolerated.

Topics: Antiemetics; Antineoplastic Agents; Benzodiazepines; Humans; Nausea; Olanzapine; Randomized Controlled Trials as Topic; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life and is one of the reasons for the discontinuation of treatment. Olanzapine is known as an atypical antipsychotic agent, but it has been reported to be effective in treating refractory CINV due to its broad and potent inhibitory activity at multiple receptors involved in the nausea and vomiting pathways. This study was conducted to assess the efficacy of olanzapine for the prevention of CINV after moderately or highly emetogenic chemotherapy. After a search of Medline (Ovid), PubMed, CNKI, Wanfang and Weipu from 1990 to October 2013, all randomised controlled trials of olanzapine for the prevention of CINV were included in this study. The meta-analysis was performed using RevMan 5.0.19 software. 6 studies involving 726 total patients were included, of which 441 were Chinese oncology patients. We found that for both general populations and Chinese populations, antiemetic regimens including olanzapine are more effective at reducing CINV than regimens that do not include olanzapine, especially in the delayed phase of CINV.

Topics: Antiemetics; Antineoplastic Agents; Benzodiazepines; Humans; Nausea; Odds Ratio; Olanzapine; Treatment Outcome; Vomiting

Olanzapine is frequently prescribed in young children for psychiatric conditions. It may be an option for chemotherapy-induced nausea and vomiting (CINV) control in children. The objective of this review was to describe the safety of olanzapine in children less than 13 years of age to determine if safety concerns would be a barrier to its use for CINV prevention.. Electronic searches were performed in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science and Scopus. All studies in English reporting adverse effects associated with olanzapine use in children younger than 13 years or with a mean/median age less than 13 years were included. Adverse outcomes were synthesized for prospective studies.. A total of 47 studies (17 prospective) involving 387 children aged 0.6-18 years were included; nine described olanzapine poisonings. Weight gain or sedation were reported in 78 % [95 % confidence interval (CI) 63-95] and 48 % (95 % CI 35-67), respectively. Extrapyramidal symptoms or electrocardiogram abnormalities were reported in 9 % (95 % CI 4-21) and 14 % (95 % CI 7-26), respectively. Elevation in liver function tests or blood glucose abnormalities were reported in 7 % (95 % CI 2-20) and 4 % (95 % CI 1-17), respectively. No deaths were attributed to olanzapine.. No studies were identified with a primary focus on evaluating safety, and the adverse effects reported in the included studies were heterogeneous.. Most adverse events associated with olanzapine use in children less than 13 years of age are of minor clinical significance. These findings support the exploration of olanzapine for the prevention of CINV in children in future trials.

Topics: Antipsychotic Agents; Appetite; Benzodiazepines; Child; Child, Preschool; Conscious Sedation; Humans; Infant; Nausea; Olanzapine; Vomiting; Weight Gain

Nausea and vomiting are common adverse events in chemotherapy. In spite of the serious effects on the quality of life and further treatment, they remain overlooked by physicians, and no standard treatment has been developed. Neurokinin-1 (NK-1) receptor antagonists and palonosetron are the major agents in the standard regimen for treating moderately and highly emetogenic chemotherapy-induced nausea and vomiting (CINV). However, NK-1 receptor antagonists first became commercially available at the end of 2013 and palonosetron has not been extensively applied in China. Olanzapine was recommended as a therapy for moderate and severe CINV in antiemesis-clinical practice guidelines in oncology in 2014 for the first time. It is an atypical antipsychotic agent, which can block multiple receptors on neurotransmitters. During more than 10 years, olanzapine has demonstrated significant effects in preventing CINV and treating breakthrough and refractor CINV, which was observed in case reports, precise retrospective studies, and phase I, II and III clinical trials, with no grade 3 to 4 adverse events. In particular, it is superior to aprepitant and dexamethasone in delayed nausea and vomiting. Therefore, this compound is worthy of further investigation.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Dexamethasone; Emetics; Humans; Isoquinolines; Morpholines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Olanzapine; Palonosetron; Quinuclidines; Vomiting

Olanzapine is an atypical antipsychotic agent of the thienobenzodiazepine class. Olanzapine blocks multiple neurotransmitter receptors, including dopaminergic (D(1), D(2), D(3), and D(4)), serotonergic (5-hydroxytryptamine 2A [5-HT(2A)], 5-HT(2C), 5-HT(3), and 5-HT(6)), adrenergic (α(1)), histaminic (H(1)), and muscarinic (M(1), M(2), M(3), and M(4)) receptors. Olanzapine has a high affinity for the 5HT(2A) receptor, which is up to 5 times greater than the dopamine receptor, resulting in less propensity to the development of extrapyramidal side effects. The affinity of olanzapine for multiple receptors has lead to the identification of olanzapine as an important agent in the treatment of delirium, nausea, and vomiting. Olanzapine has been demonstrated to have opioid-sparing properties. Olanzapine is principally metabolized by glucuronidation, with a smaller metabolic contribution from the cytochrome oxidase system. Adverse effects of olanzapine include somnolence, postural hypotension, constipation, dizziness, restlessness, and weight gain. The purpose of this article is to outline the pharmacodynamics, pharmacology, and evidence for the use of olanzapine in palliative care.

Topics: Benzodiazepines; Clinical Trials as Topic; Critical Illness; Dementia; Drug Interactions; Humans; Nausea; Neoplasms; Olanzapine; Pain Management; Palliative Care; Selective Serotonin Reuptake Inhibitors; Vomiting

Nausea and vomiting are often encountered in palliative care patients. Multiple medications are available to provide relief. However, several drug combinations are usually used to treat emesis. Current research has identified several receptors that trigger nausea and vomiting, hence the difficulty of using only 1 medication to provide relief. Olanzapine is a drug approved for treatment of schizophrenia and mania. It blocks multiple neurotransmitters dopaminergic, serotonergic, adrenergic (alpha(1)), histaminergic, and muscarinic receptors. Most of these receptors are also involved in causing emesis. Studies have shown that olanzapine could be used to treat nausea and vomiting with promising results.

Topics: Antiemetics; Antineoplastic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Evidence-Based Medicine; Humans; Nausea; Neoplasms; Olanzapine; Quality of Life; Treatment Outcome; Vomiting

Only a few studies have investigated the effect of antiemetic therapy in patients treated with multiple-day or multiple cycles of chemotherapy. The present review will assess the available data, highlight the current recommendations and draw attention towards the remaining problems in this field of antiemetic treatment.. Evidence-based guidelines recommend a combination of a 5-HT3-receptor antagonist and dexamethasone in the prophylaxis of nausea and vomiting in multiple-day cisplatin-based chemotherapy. In patients treated with multiple cycles of chemotherapy the addition of a NK1-receptor antagonist aprepitant to standard antiemetic therapy has increased the antiemetic effect, and multiple cycle extension studies have demonstrated that this increment in effect is sustained during multiple cycles of chemotherapy. A recent study indicated that the dopamine D2-receptor antagonist metopimazine has some additive effect on delayed symptoms induced by multiple-day chemotherapy.. The development of the NK1-receptor antagonist aprepitant has significantly improved the antiemetic control in patients treated with multiple cycles of chemotherapy. Far too many patients still experience considerable emetic side effects. The effect of aprepitant in multiple-day chemotherapy has yet to be defined. The effect of new antiemetic agents such as palonosetron and olanzapine also needs to be investigated in randomized trials.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Cisplatin; Dexamethasone; Dopamine D2 Receptor Antagonists; Drug Administration Schedule; Humans; Isonipecotic Acids; Isoquinolines; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Olanzapine; Palonosetron; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Vomiting

Patients consider nausea and vomiting among the worst side effects of chemotherapy. This paper reviews the development of antiemetics during the past 12 years, focusing on the neurokinin (NK)1-receptor antagonist, aprepitant, and the new 5-HT3-receptor antagonist palonosetron. Evidence-based recommendations for prophylaxis of chemotherapy-induced nausea and vomiting are given. Antiemetics are effective in prevention of vomiting, but less effective against nausea. Therefore studies with potential new antiemetics, such as olanzapine and ghrelin are awaited with suspense.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Dexamethasone; Drug Interactions; Drug Therapy, Combination; Evidence-Based Medicine; Ghrelin; Glucocorticoids; Granisetron; Humans; Isoquinolines; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Olanzapine; Palonosetron; Peptide Hormones; Practice Guidelines as Topic; Quinuclidines; Serotonin Antagonists; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles and patient risk factors (female gender, younger age, no alcohol consumption, history of motion sickness) are the major risk factors for CINV. The use of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists plus dexamethasone has significantly improved the control of acute CINV, but delayed nausea and vomiting remains a significant clinical problem. Two new agents, palonosetron and aprepitant, have recently been approved for the prevention of both acute and delayed CINV. Palonosetron is a 5-HT3 receptor antagonist with a longer half-life and a higher binding affinity than first-generation 5-HT3 receptor antagonists. Aprepitant is the first agent available in the new drug class of neurokinin-1 receptor (NK-1) antagonists. There are a number of 5-HT3 receptor antagonists and NK-1 receptor antagonists currently in Phase II and III clinical trials. Revised antiemetic guidelines for the prevention of CINV are reviewed. Future studies may consider the use of palonosetron and aprepitant with current and other new agents (olanzapine, gabapentin) in moderately and highly emetogenic chemotherapy, as well as in the clinical settings of multiple-day chemotherapy and bone marrow transplantation.

Topics: Antiemetics; Antineoplastic Agents; Antipsychotic Agents; Aprepitant; Benzodiazepines; Brain; Dexamethasone; Drug Therapy, Combination; Gastrointestinal Tract; Humans; Isoquinolines; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Olanzapine; Palonosetron; Quinuclidines; Randomized Controlled Trials as Topic; Receptors, Neurokinin-1; Receptors, Serotonin, 5-HT3; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Vagus Nerve; Vomiting

The antibody-drug conjugate trastuzumab deruxtecan (T-DXd) has led to a change in the clinical management of breast cancer. Nausea and vomiting are the most common adverse events of T-DXd, which cannot be completely alleviated by standard prophylactic regimens. Olanzapine is particularly effective in preventing delayed nausea caused by chemotherapy. In this study, we will evaluate the efficacy of olanzapine in managing persistent nausea and vomiting during T-DXd treatment.. The ERICA study is a multicentre, placebo-controlled, double-blind, randomised phase II study with the aim to evaluate the antiemetic effects of the prophylactic olanzapine (5 mg orally, on days 1-6) or placebo combined with a 1,5-hydroxytryptamine-3 (5-HT. The study protocol is approved by the West Japan Oncology Group protocol review committee and the SHOWA University Clinical Research Review Board. The study results will be presented at international conferences and published in a peer-reviewed journal.. jRCTs031210410.

Topics: Antiemetics; Antineoplastic Agents; Breast Neoplasms; Clinical Trials, Phase II as Topic; Double-Blind Method; Female; Humans; Immunoconjugates; Multicenter Studies as Topic; Nausea; Olanzapine; Randomized Controlled Trials as Topic; Vomiting

It is unknown whether olanzapine combined with triplet antemetic therapy is effective for all patients undergoing highly emetogenic chemotherapy. A secondary analysis of randomized clinical trials using olanzapine may provide insight into the effectiveness of olanzapine for chemotherapy-induced nausea and vomiting (CINV), including cisplatin.. To examine the add-on effect of olanzapine according to risk factors for CINV.. This preplanned secondary analysis evaluated results of the J-FORCE trial, a large double-blind, placebo-controlled phase 3 randomized clinical trial conducted in Japan from February 9, 2017, to July 18, 2018. Participants were enrolled from 26 participating hospitals across Japan and included patients aged 20 to 75 years who had a malignant tumor and were cisplatin-naive. The efficacy analysis population of the J-FORCE trial was analyzed according to allocation adjustment factors (sex [male or female], age [≥55 years or <55 years], and cisplatin dose [≥70 mg/m2 or <70 mg/m2]) and patient-related risk factors (history of motion sickness, drinking habit [defined as alcoholic drinks consumption in excess of occasional drinking], and history of morning sickness during pregnancy). Statistical analysis was performed from February 18 to April 18, 2020.. Patients were randomized 1:1 to receive 5 mg of olanzapine or placebo combined with standard triplet antiemetic therapy.. The primary end point was complete response (CR, defined as no vomiting and no use of rescue medication) in the delayed phase (24-120 hours after cisplatin-based chemotherapy administration). Secondary end points were CR, complete control, and total control in the acute, delayed, and overall phases for 6 CINV risk factors as well as time to treatment failure. The CR point estimates and 95% CIs of the differences between groups were calculated, and a Mantel-Haenszel test was performed.. Of the 705 patients (mean [SD] age, 63.0 [9.2] years; 471 males [66.8%]) included in the efficacy analysis population; 581 patients (82.4%) were 55 years or older, and 526 (74.6%) were treated with a cisplatin dose of 70 mg/m2 or more. Risk difference (RD) for a CR in the delayed phase was significantly greater in the olanzapine group than the placebo group in males (RD, 12.6% [95% CI, 5.0%-20.1%]; P = .001); in females (RD, 14.5% [95% CI, 2.2%-26.3%]; P = .02); in those 55 years or older (RD, 11.1% [95% CI, 3.9%-18.2%]; P = .003) or younger than 55 years (RD, 23.6% [95% CI, 7.3%-38.3%]; P = .005); for a cisplatin dose of 70 mg/m2 or more (RD, 13.5% [95% CI, 5.9%-21.0%]; P < .001); for those without a history of motion sickness (RD, 13.9% [95% CI, 6.9%-20.6%]; P < .001); for those with a drinking habit (RD, 14.9% [95% CI, 6.1%-23.4%]; P = .001) or without a drinking habit (RD, 12.0% [95% CI, 2.5%-21.3%]; P = .01); and for those with a history of morning sickness during pregnancy (RD, 27.2% [9.7%-42.6%]; P = .002). In other subgroups, a delayed CR was higher in the olanzapine group than the placebo group, although not significantly higher.. Results of this study suggest a benefit of using 5 mg of olanzapine plus triplet antiemetic therapy to counter CINV regardless of the presence or absence of risk factors.. University Hospital Medical Information Network Clinical Trials Registry Identifier: UMIN000024676.

Topics: Antiemetics; Cisplatin; Female; Humans; Male; Middle Aged; Morning Sickness; Motion Sickness; Nausea; Olanzapine; Pregnancy; Vomiting

A protocol was developed to evaluate the value of an NK-1 receptor antagonist for preventing nausea and vomiting resulting from highly emetogenic chemotherapy when an olanzapine-based antiemetogenic regimen was used.. A221602, a prospective double-blind, placebo-controlled clinical trial, was developed to compare 2 -olanzapine-containing antiemetic regimens, one with an NK-1 receptor antagonist (aprepitant or fosaprepitant) and one without. Trial patients had a malignant disease for which they received intravenous highly emetogenic chemotherapy (single day cisplatin ≥ 70 mg/m2 or doxorubicin plus cyclophosphamide on 1 day). Patients on both arms received commonly administered doses of a 5-HT3 receptor antagonist, dexamethasone, and olanzapine. Additionally, patients were randomized to receive an NK-1 receptor antagonist (fosaprepitant 150 mg IV or aprepitant 130 mg IV) or a corresponding placebo. The primary objective was to compare the proportion of patients with no nausea for 5 days following chemotherapy between the 2 study arms. This trial was designed to test for the noninferiority of deleting the NK-1 receptor antagonist, with noninferiority defined as a decrease in freedom from nausea by less than 10%.. A total of 690 patients were entered on this trial, 50% on each arm. The proportion of patients without nausea for the complete 5-day study period was 7.4% lower (upper limit of the one-sided 95% confidence interval was 13.5%) in the arm without an NK-1 receptor antagonist compared with the arm with an NK-1 receptor antagonist.. This trial did not provide sufficient evidence to support that deletion of the NK-1 receptor antagonist was as good as keeping it, as a part of a 4-drug antiemetic regimen for highly emetogenic chemotherapy (ClinicalTrials.gov Identifier: NCT03578081).

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Dexamethasone; Double-Blind Method; Humans; Nausea; Olanzapine; Prospective Studies; Receptors, Neurokinin-1; Vomiting

We aim to investigate the correlation between gene polymorphisms and cisplatin chemotherapy-induced nausea and vomiting (CINV), which was prevented by olanzapine or aprepitant triple antiemetic regimen.. Before chemotherapy, the blood samples of 89 malignant tumor patients who received multi-day chemotherapy with cisplatin were collected for sequencing and typing. As there were duplicate patients enrolled in different chemotherapy cycles, there were a total of 190 cases. The patients were divided into two groups randomly, who received the triple antiemetic regimen of olanzapine or aprepitant combined with 5-HT3RA and dexamethasone. The main evaluation indicators were the total protection (TP) rate in the acute phase (0-24 h), the delayed phase (25-120 h) and the overall phase (0-120 h).. Univariate analysis was performed on genetic loci that reached H-W balance with TP. In the olanzapine group, increased TP in the acute phase was associated with HTR3A rs1176719 non-GG (P < 0.05) genotype etc. Increased TP in the delayed phase was associated with HTR3A rs1176719 non-GG (P < 0.05) genotype etc. In the aprepitant group, increased TP in the acute phase was associated with the MTHFR rs1801131 TT (P < 0.05) genotype etc. Increased TP in the delayed phase was associated with HTR3A rs1062613 CC (P < 0.05) genetype ect. Multivariate Logistic regression analysis showed that HTR3B rs7943062GG (P < 0.05) genotype etc. were correlated with increased TP in the delayed phase. MTHFR rs1801131TT genotype was associated with increased TP in the acute phase (P < 0.05) and delayed phase (P < 0.05).. This study found that gene polymorphisms, including HTR3B (rs1062613, rs1176719, rs2276303), HTR3B (rs45460698, rs7943062), HTR3C (rs6766410), ERCC1 (rs3212986), ERCC4 (rs744154) and MTHFR(rs1801131), may be independent prognostic factors for CINV.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Humans; Nausea; Olanzapine; Polymorphism, Genetic; Vomiting

Clinical observations of cancer patients treated with selinexor have reported high incidence of nausea and anorexia. The study objective was to investigate the adoption of prophylactic olanzapine for the prevention of nausea, vomiting and anorexia in cancer patients receiving selinexor and standard chemotherapy.. We retrospectively reviewed supportive care interventions in patients receiving selinexor and recorded frequency of adverse events (NCI-CTAE). Association between categorical variables were analyzed using Fisher's exact tests; repeated measures analysis was performed to assess weight changes over time.. Of 124 evaluable patients, 83 (66.9%) were female, 93 were white (75.0%), and the most common cancer was ovarian (N = 30, 24.2%). One hundred and four patients (83.9%) received olanzapine, of which 93 (89.4%) were prophylactically treated, the majority (86.5%) receiving low 2.5 mg daily dose. Other anti-emetics included ondansetron in 90 patients (72.6%), dexamethasone prescribed in 50 patients (40.3%) and metoclopramide in 49 patients (39.5%), while aprepitant/fosaprepitant (N = 2, 1.6%) were prescribed infrequently. Cancer patients receiving prophylactic olanzapine (N = 93) compared to patients who never received olanzapine (N = 20) had more Grade 1 + anorexia (31.2% vs 20.0%), less nausea (53.8% vs 70.0%), less vomiting (33.3% vs 40.0%), and increased hyperglycemia (29.0% vs 10.0%), but differences were non-statistically significant. In addition, there was minimal weight loss over time in both groups and no statistically significant differences in weight loss between groups.. Prophylactic olanzapine decreased nausea, vomiting and maintained weight over 3 months but did not prevent anorexia in patients receiving selinexor and chemotherapy. Low dose olanzapine was well tolerated but associated with hyperglycemia.

Topics: Adult; Aged; Anorexia; Antiemetics; Female; Humans; Hydrazines; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Triazoles; Vomiting; Young Adult

In this trial, we evaluated the safety and efficacy of olanzapine in children receiving highly emetogenic chemotherapy.. In this study, patients aged 3 to 18 years were randomly assigned to either the olanzapine group or the placebo group. All patients received intravenous ondansetron and dexamethasone 30 minutes before highly emetogenic chemotherapy, followed by oral ondansetron for 48 hours. Participants in the olanzapine group received olanzapine once daily on days 1 and 2, while those in the control group received a placebo in the same dosage and schedule. The primary objective was: (a) to compare the complete control rates of vomiting in the delayed phase and (b) to compare the complete control rates of vomiting in acute and overall phases. The secondary objective was to evaluate the safety of olanzapine and the need for rescue medications.. A total of 128 patients were randomly assigned either to the olanzapine group (n=63) or the control group (n=65). Complete control of vomiting between olanzapine and placebo group was 73% versus 48% ( P =0.005) in the delayed phase, 60% versus 54% ( P =0.46) in the acute phase, and 48% versus 34% ( P =0.117) in the overall phase, respectively. Grades 1 and 2 sedation was greater in the olanzapine group (46% vs. 14%; P <0.001). A significantly higher proportion of patients in the placebo group required rescue medications for vomiting compared with in the olanzapine group ( P =0.025).. Olanzapine significantly improved complete control of vomiting in the delayed phase. A considerably lesser proportion of patients in the olanzapine group needed rescue medications.

Topics: Antiemetics; Antineoplastic Agents; Child; Dexamethasone; Double-Blind Method; Humans; Nausea; Neoplasms; Olanzapine; Ondansetron; Vomiting

Triple antiemetic therapy with neurokinin-1 receptor antagonist, 5-hydroxytryptamine type 3 receptor antagonist, and dexamethasone has been widely recommended for high emetogenic chemotherapeutic (HEC) agents and regimens, including anthracycline combined with cyclophosphamide (AC). The addition of olanzapine (OLZ) 5 mg or 10 mg to the recommended triple antiemetic therapy has demonstrated superiority in antiemetic efficacy compared with the standard triplet therapy for a cisplatin-based HEC regimen. Although OLZ plus the triple antiemetic treatment may also be effective for patients on an AC-based HEC regimen, no study has investigated its efficacy at a lower dose of 5 mg.. To assess whether 5 mg OLZ, as compared with placebo, in combination with triple combination therapy, significantly improves nausea and vomiting, we are conducting a randomised, parallel-group controlled clinical trial with a total of 500 patients at 15 study centres in Japan. The primary outcome is the complete response rate, defined as no emetic episodes and no use of rescue medication during 120 hours after the initiation of chemotherapy. Treatment group comparison for the primary endpoint will be done by using the Cochran-Mantel-Haenszel test.. The study was approved by the institutional review board of Juntendo University Hospital and relevant approval was obtained from all participating centres. All participants will be required to provide written informed consent. The trial results will be reported at conferences and in peer-reviewed journals.. Japan Registry of Clinical Trials (jRCT) jRCT1031200134; protocol date: 30 July 2020, version: 1.3, approval: 25 August 2020.

Topics: Anthracyclines; Antibiotics, Antineoplastic; Antiemetics; Antineoplastic Agents; Breast Neoplasms; Cyclophosphamide; Double-Blind Method; Female; Humans; Japan; Nausea; Olanzapine; Randomized Controlled Trials as Topic; Serotonin 5-HT3 Receptor Antagonists; Vomiting

Olanzapine has been reported to be an effective antiemetic in patients receiving carboplatin-based chemotherapy. However, the efficacy of a neurokinin-1 receptor antagonist (NK. Data were pooled for 140 patients receiving carboplatin-based chemotherapy from three multicenter, prospective, single-arm, open-label phase II studies that evaluated the efficacy and safety of olanzapine for chemotherapy-induced nausea and vomiting. The propensity score of the co-administration of NK. The complete response rate (without emetic episodes or with no administration of rescue medication) in the overall period (0-120 h post carboplatin administration) was 93.5% in the non-NK. The findings suggest that antiemetic regimens consisting of olanzapine, 5HT

Topics: Carboplatin; Dexamethasone; Humans; Nausea; Neurokinin-1 Receptor Antagonists; Olanzapine; Propensity Score; Prospective Studies; Serotonin 5-HT3 Receptor Antagonists; Vomiting

A prospective randomized controlled trial was conducted to compare 5 mg olanzapine plus standard triple antiemetic therapy for the prevention of nausea and vomiting induced by multiple-day cisplatin chemotherapy.. (1) The primary endpoint CR during OP was 76.0% (45/59) vs 67.0% (41/61) between the quadruple group and triplet group (P = 0.271). The secondary endpoint CR during the AP was significantly higher in the quadruple group than in the triplet group, which was 100.0% (59/59) vs 93.0% (57/61) (P = 0.045). The difference of CR during delayed phase between the groups was especially higher in the quadruple group compared to the triplet group (76.0% (45/59) vs 67.0% (41/61) (P = 0.271)). The rate of patients who achieved total protection in the overall phase was also higher in the quadruple group than the triplet group (28.8% (17/59) vs 23.0% (14/61) (P = 0.463)). During the OP, the incidence of no vomiting in the quadruple group and the triplet group was 93.2% (55/59) vs 80.3% (49/61) (P = 0.038), respectively. (2) Kaplan-Meier curves of time to first emesis were obviously longer in the quadruple group compared with the triplet group (P = 0.031). According to FLIE, no impact of CINV on daily life was defined as total score of questionnaire > 108; this study exhibited identical life quality between two groups. (3) The most common aprepitant- or olanzapine-related AEs included sedation, fatigue, and constipation. The occurrences between two groups were identical.. It may been recommended that 5 mg olanzapine plus tropisetron and dexamethasone, omitting aprepitant triplet regimen as an alternative therapy in prevention CINV induced by multiple-day cisplatin chemotherapy due to the excellent CINV control rate and safety.

Topics: Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Dexamethasone; Humans; Nausea; Olanzapine; Prospective Studies; Quality of Life; Tropisetron; Vomiting

To compare the efficacy and safety of two different dosage levels of olanzapine for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving high emetic risk chemotherapy.. This study was a randomized, double-blind, controlled trial designed to show non-inferiority in the efficacy of olanzapine 5 mg compared to 10 mg in patients treated with high dose cisplatin or doxorubicin/cyclophosphamide. Non-inferiority was defined as a lower margin of the 95% confidence interval (95% CI) that not lower than the margin set at -25%.. A total of 140 patients were randomized to 5 mg group (n=70) or 10 mg group (n=70) of olanzapine. The complete response (CR) rate in the overall phase of olanzapine 5 and 10 mg was 58.6% v 62.9% (95%CI: -20.4, 11.8). The CR rate comparison between olanzapine 5 and 10 mg was 81.4% v 74.3% (95%CI: -6-6, 20.8) and 66.7% v 76.1% (95%CI: -23.5, 6.3) for the acute and delayed phase, respectively. No nausea rates in acute, delayed and overall phase were 70.0% v 68.6% (95%CI: -13.8, 16.6), 45.7% v 48.6% (95%CI: -19.4, 13.6) and 43.5% v 47.9% (95%CI: -19.2, 13.6). The rate of adverse events (AE) including somnolence were not different between the 5 and 10 mg groups.. The two dosage levels of olanzapine were not different in terms of the efficacy and AE in the prophylaxis of CINV.

Topics: Antiemetics; Antineoplastic Agents; Dexamethasone; Emetics; Humans; Nausea; Neurokinin-1 Receptor Antagonists; Olanzapine; Vomiting

To assess adverse events (AEs) and safety of aripiprazole (ARI) and olanzapine (OLA) treatment.. Twenty-four healthy volunteers receiving five daily oral doses of 10 mg ARI and 5 mg OLA in a crossover clinical trial were genotyped for 46 polymorphisms in 14 genes by qPCR. Drug plasma concentrations were measured by high-performance liquid chromatography tandem mass spectrometry. Blood pressure (BP) and 12-lead electrocardiogram were measured in supine position. AEs were also recorded.. ARI decreased diastolic BP on the first day and decreased QTc on the third and fifth day. OLA had a systolic and diastolic BP, heart rate and QTc lowering effect on the first day. Polymorphisms in ADRA2A, COMT, DRD3 and HTR2A genes were significantly associated to these changes. The most frequent adverse drug reactions (ADRs) to ARI were somnolence, headache, insomnia, dizziness, restlessness, palpitations, akathisia and nausea while were somnolence, dizziness, asthenia, constipation, dry mouth, headache and nausea to OLA. Additionally, HTR2A, HTR2C, DRD2, DRD3, OPRM1, UGT1A1 and CYP1A2 polymorphisms had a role in the development of ADRs.. OLA induced more cardiovascular changes; however, more ADRs were registered to ARI. In addition, some polymorphisms may explain the difference in the incidence of these effects among subjects.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Blood Pressure; Dizziness; Electrocardiography; Female; Headache; Heart Rate; Humans; Male; Nausea; Olanzapine; Sleepiness

Lay abstract Methods to prevent chemotherapy-induced nausea and vomiting (CINV) are often not sufficient for patients. Olanzapine, along with other similar drugs (antiemetics), improved control but is often sedating. In this study, a lower dose of olanzapine was compared with the conventional dose. Patients on cancer chemotherapy, which has high occurrence of nausea and vomiting, were given either the low dose or the conventional dose of olanzapine for 3 days, in addition to some other antiemetic agents. Control of nausea and vomiting was reasonably achieved with both doses of olanzapine. The lower dose was significantly less sedating. There were no serious side effects with either doses.

Topics: Anti-Inflammatory Agents; Antiemetics; Antineoplastic Agents; Dexamethasone; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Ondansetron; Prospective Studies; Quality of Life; Vomiting

Olanzapine is an inexpensive and durable agent for the treatment of chemotherapy-induced nausea and vomiting and is also superior to neurokinin-1 receptor antagonists in the control of nausea. This study aimed to investigate the efficacy and safety of a low dose of 5 mg olanzapine plus granisetron and dexamethasone for treatment of carboplatin (CBDCA)-induced nausea and vomiting in patients with thoracic malignancies.. We conducted a prospective, open-label, single-arm, multicenter, phase II trial in four centers in Japan. Registered patients were scheduled to receive area under the curve (AUC) ≥5 mg/mL per minute of CBDCA and had never received moderately to highly emetogenic chemotherapy. Patients received olanzapine 5 mg/day orally after supper for 4 days, in combination with granisetron and dexamethasone. Primary endpoint was complete response (CR; no emesis and no use of rescue medication) rate during the overall phase (0-120 hours).. Between February 2018 and June 2020, 51 patients were enrolled, and 50 patients were evaluated. The CR rates in the overall (0-120 hours), acute (0-24 hours), and delayed phases (24-120 hours) were 94.0%, 100%, and 94.0%, respectively. No grade 3 or higher adverse effects of olanzapine were observed.. Prophylactic antiemetic therapy with a low dose of 5 mg olanzapine plus granisetron and dexamethasone showed durable efficacy with an acceptable safety profile. This three-drug combination appears to be a reasonable treatment approach in patients with thoracic malignancies receiving an AUC ≥5 mg/mL per minute of CBDCA-based regimen. Clinical trial identification number: UMIN000031267.. The results of this phase II trial indicated that the prophylactic administration of low-dose of 5 mg olanzapine combined with granisetron and dexamethasone has promising activity with acceptable safety profile in patients with thoracic malignancy receiving high-dose carboplatin chemotherapy.

Topics: Carboplatin; Dexamethasone; Granisetron; Humans; Japan; Nausea; Olanzapine; Prospective Studies; Thoracic Neoplasms; Vomiting

The efficacy of olanzapine as an antiemetic agent in cancer chemotherapy has been demonstrated. However, few high-quality reports are available on the evaluation of olanzapine's efficacy and safety at a low dose of 5 mg among patients treated with carboplatin regimens. Therefore, in this study, we investigated the efficacy and safety of 5 mg olanzapine for managing nausea and vomiting in cancer patients receiving carboplatin regimens and identified patient-related risk factors for carboplatin regimen-induced nausea and vomiting treated with 5 mg olanzapine.. Data were pooled for 140 patients from three multicenter, prospective, single-arm, open-label phase II studies evaluating the efficacy and safety of olanzapine for managing nausea and vomiting induced by carboplatin-based chemotherapy. Multivariable logistic regression analyses were performed to determine the patient-related risk factors.. Regarding the endpoints of carboplatin regimen-induced nausea and vomiting control, the complete response, complete control, and total control rates during the overall study period were 87.9, 86.4, and 72.9%, respectively. No treatment-related adverse events of grade 3 or higher were observed. The multivariable logistic regression models revealed that only younger age was significantly associated with an increased risk of non-total control. Surprisingly, there was no significant difference in CINV control between the patients treated with or without neurokinin-1 receptor antagonist.. The findings suggest that antiemetic regimens containing low-dose (5 mg) olanzapine could be effective and safe for patients receiving carboplatin-based chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Carboplatin; Female; Humans; Male; Middle Aged; Nausea; Olanzapine; Prospective Studies; Vomiting

To evaluate the efficacy and safety of the addition of olanzapine to ondansetron and dexamethasone for chemotherapy-induced nausea vomiting (CINV) prevention in patients receiving highly emetogenic chemotherapy (HEC).. In this randomized, double-blind, placebo-controlled, crossover study, we randomly assigned chemotherapy-naïve patients receiving HEC to receive olanzapine or placebo in addition to ondansetron and dexamethasone. All subjects were crossed over to another treatment arm on second-cycle chemotherapy. The primary endpoint was complete response (CR) rate defined as no vomiting and no use of rescue drugs.. At the first cycle, there were significantly more patients with CR in the olanzapine group than in the placebo group in overall phase (68.7% vs. 25.0%, p < 0.001), acute phase (0-24 h) (75.0% vs. 31.2%, p < 0.001) and delayed phase (24-120 h) (68.7% vs. 43.7%, p = 0.038). After crossover, there were significantly more patients with CR in the olanzapine group than in the placebo group in overall phase (67.2% vs. 25.0%, p < 0.001), acute phase (71.9% vs. 32.8%, p < 0.001) and delayed phase (67.2% vs. 37.5%, p < 0.001). In crossover analysis, the olanzapine group had significantly lower mean nausea (1.28 vs. 3.05, p < 0.001) and fatigue (3.5 vs. 4.58, p < 0.001) scores but higher mean appetite (2.5 vs. 1.55, p = 0.003) and sleepiness (3.26 vs. 2.2, p < 0.001) scores. There were no grade 3 and 4 anti-emetic-drug-related toxicities. Mean QT interval changes did not different between two groups (-4.30 vs. -1.86, p = 0.69).. The addition of olanzapine to ondansetron and dexamethasone significantly improved CINV prevention and was safe in patients receiving HEC.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Dexamethasone; Double-Blind Method; Female; Humans; Male; Middle Aged; Nausea; Olanzapine; Ondansetron; Treatment Outcome; Vomiting

The aim of this study was to investigate the efficacy and safety of prophylactic administration of 5 mg olanzapine (OLZ) combined with neurokinin 1 receptor antagonist (NK. We conducted a single-arm, multi-institution, phase II study. Gynecological cancer patients scheduled to receive AUC ≥4 mg/mL/min CBDCA were enrolled. All patients received 5 mg OLZ (once daily after supper on days 1-4) combined with NK. Between May 2018 and June 2019, 60 patients were enrolled from 3 institutions in Japan. A total of 57 patients who met the criteria were included in the efficacy and safety analysis. The CR rate for the overall phase was 78.9%. Acute (0-24 h) and delayed phases (24-120 h) were 96.5% and 80.7%, respectively. Somnolence was observed in 73.7% patients. However, somnolence of grade 2 or higher was observed in only 3.5% of cases. There were no grade 3 or 4 toxicities associated with OLZ.. Preventive use of OLZ combined with standard triplet therapy had promising activity with manageable safety, suggesting that this combination could be an effective standard treatment option for patients with AUC ≥4 mg/mL/min CBDCA combination therapy.

Topics: Adult; Aged; Antiemetics; Aprepitant; Carboplatin; Dexamethasone; Female; Genital Neoplasms, Female; Granisetron; Humans; Middle Aged; Nausea; Olanzapine; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) are distressing symptoms. This randomized study evaluated the antiemetic efficacies of standard antiemetic regimen with/without olanzapine.. Eligible patients were chemotherapy-naive Chinese breast cancer patients who were planned for (neo)adjuvant doxorubicin/cyclophosphamide. Antiemetic regimen for all studied population included aprepitant, ondansetron and dexamethasone; patients were randomized to Olanzapine (with olanzapine) or Standard arms (without olanzapine). Patients filled in self-reported diaries and completed visual analogue scales for nausea, as well as Functional Living Index-Emesis questionnaires. Blood profiles including fasting glucose and lipids were monitored.. 120 patients were randomized. In Cycle 1 doxorubicin/cyclophosphamide, the Olanzapine arm had significantly higher rates of "Complete Response" than the Standard arm: 65.0% vs 38.3% in the overall period (p = 0.0035), 70.0% vs 51.7% in the acute period (p = 0.0397) and 92.9% vs 74.2% in the delayed period (p = 0.0254). Olanzapine arm also had significantly higher rates of "No significant nausea" and "No nausea" during all 3 time-frames and better QOL. Similar findings were also revealed throughout multiple cycles. Pre-study abnormalities in glucose and lipids occurred in 39.7% and 34.2% of the studied population respectively; there were no differences in these parameters between the two arms at end-of-study assessment.. The addition of olanzapine to standard aprepitant-based antiemetic regimen provides clinically meaningful improvement in controlling CINV. This was associated with a positive impact on QOL and tolerable toxicity profiles among Chinese breast cancer patients receiving doxorubicin/cyclophosphamide chemotherapy. Further studies on metabolic profiles of breast cancer patients are warranted.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; China; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Humans; Middle Aged; Nausea; Olanzapine; Ondansetron; Vomiting

We assessed the efficacy of aprepitant (APR) or 10 or 5 mg OLN (OLN10 or OLN5) plus ondansetron and dexamethasone for chemotherapy-induced nausea/vomiting (CINV) prophylaxis in patients receiving high-emetogenic chemotherapy (HEC).. Patients who received doxorubicin + cyclophosphamide or cisplatin were given intravenous ondansetron and dexamethasone prior to chemotherapy and oral dexamethasone on days 2-4 and randomized 1:1:1 to receive APR125 on day 1 and APR80 on days 2-3 or OLN10 or OLN5 on days 1-4. Matched placebo controls were used. The primary endpoint was no nausea in ≤ 120 h. Secondary endpoints included CINV severity, complete response (CR) rate, adverse effects (AE), and quality of life.. Of 141 patients, 104 received AC and 37 received cisplatin. The no-nausea rates were 33% (APR), 43.2% (OLN10; p = 0.24), and 37% (OLN5; p = 0.87). Grades 2-4 nausea were experienced by fewer patients for OLN10 than for APR (24-120 h, 8.7% vs. 27.7%, respectively; p = 0.02; overall period, 19.6% vs. 40.4%, respectively; p = 0.03). The median visual analog scale nausea score from 24 to 120 h was significantly lower for OLN10 (2.3) than for APR (1.2, p = 0.03). The degrees of vomiting, CR, and AE were similar between the APR and OLN10 groups. CINV was similar between the OLN5 and APR groups.. Nausea was less severe for OLN10 than for APR in patients receiving HEC, but other measures were similar. CINV prevention efficacy was comparable between OLN5 and APR.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Chemoprevention; Cisplatin; Cyclophosphamide; Dexamethasone; Dose-Response Relationship, Drug; Double-Blind Method; Doxorubicin; Drug Therapy, Combination; Emetics; Female; Humans; Induction Chemotherapy; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Ondansetron; Placebos; Quality of Life; Treatment Outcome; Vomiting; Young Adult

Nausea and vomiting, unrelated to chemotherapy, can be substantial symptoms in patients with advanced cancer.. To evaluate the utility of olanzapine for treating chronic nausea/vomiting, unrelated to chemotherapy, in patients with advanced cancer.. 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).. Patients received olanzapine (5 mg) or a placebo, orally, daily for 7 days.. 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.. 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.. 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.. ClinicalTrials.gov Identifier: NCT03137121.

Topics: Adult; Aged; Antiemetics; Double-Blind Method; Female; Humans; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Pilot Projects; Vomiting

Despite triple antiemetic therapy use for breast cancer patients receiving emetogenic chemotherapy, nausea remains a clinical challenge. We evaluated adding olanzapine (5 mg) to triple therapy on nausea control in patients at high personal risk of chemotherapy-induced nausea and vomiting (CINV).. This multi-centre, placebo-controlled, double-blind trial randomized breast cancer patients scheduled to receive neo/adjuvant chemotherapy with anthracycline-cyclophosphamide or platinum-based chemotherapy to olanzapine (5 mg, days 1-4) or placebo. Primary endpoint was frequency of self-reported significant nausea, repeated for all cycles of chemotherapy. Secondary endpoints included: duration of nausea, overall total control of CINV, Health Related Quality of Life (HRQoL) using FLIE questionnaire, use of rescue mediation and treatment-related adverse events.. 218 eligible patients were randomised to placebo (105) or olanzapine (113). From days 0-5 following each cycle of chemotherapy, 41.3% (95%CI: 36.1-46.7%) of patients in the placebo group reported significant nausea compared to 27.7% (95%CI: 23.2-32.4%) in the olanzapine group (p = 0.001). Across all cycles of chemotherapy, patients receiving olanzapine experienced a statistically significant improvement in HRQoL (p < 0.001). Grade 1/2 sedation was the most commonly side effect reported at 40.8% in the placebo group vs. 54.1% with olanzapine (p < 0.001).. In patients at high personal risk of CINV, the addition of olanzapine 5 mg daily to standard antiemetic therapy significantly improves the control of nausea, HRQoL, with no unexpected toxicities.

Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Double-Blind Method; Female; Humans; Middle Aged; Nausea; Olanzapine; Quality of Life; Standard of Care; Treatment Outcome; Vomiting; Young Adult

Since most of Thai cancer patients receiving high emetogenic chemotherapy do not have access to neurokinin-1 (NK-1) receptor antagonists or palonosetron as recommended by international guidelines for chemotherapy-induced nausea and vomiting (CINV) prevention. We decided to evaluate the efficacy of olanzapine with the real-life practice antiemetic drugs ondansetron and dexamethasone, in prevention of CINV resulting from doxorubicin plus cyclophosphamide regimen in early-stage breast cancer patients.. In this randomized, double-blind, placebo-controlled trial, we compared olanzapine with a placebo in combination with ondansetron and dexamethasone in early-stage breast cancer patients receiving doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2. The intervention group received olanzapine 10 mg orally while the control group received a matching placebo daily on day 1 through day 4. All patients received ondansetron 8 mg and dexamethasone 20 mg intravenously 30 minutes before chemotherapy administration and then dexamethasone 10 mg daily orally from day 1 through day 4. The primary endpoint was no nausea rate in the early period. The secondary endpoints were no nausea rate in the delayed and overall periods and a complete response (no vomiting and no use of rescue drug). Outcomes were determined by patients' self-reported daily records of episodes of vomiting or retching, use of rescue therapy and daily levels of nausea based on a visual-analogue scale from the first cycle of chemotherapy.. A total of 39 female patients were randomized in a 1:1 ratio to receive olanzapine (20 patients) or a matching placebo (19 patients). A significantly greater proportion of patients reported no nausea in the olanzapine group than in the placebo group in both the early period (0-24 hours after chemotherapy) and the overall period (0-120 hours after chemotherapy). Patients who reported no nausea in the early period accounted for 50% and 10.5% in the olanzapine group and in the placebo group respectively (P=0.008). In the overall period, 30.0% and 0% of patients reported no nausea in the olanzapine and placebo groups respectively (P=0.009). In the early period, there was a significantly different complete response rate between two treatment groups; 75.0% in the olanzapine group and 36.8% in the placebo group (P=0.016). Overall treatment-related adverse events were not significantly different between the two study groups except that somnolence was significantly more common in the olanzapine group than in the placebo group.. Olanzapine 10 mg combined with ondansetron and dexamethasone was more effective than a placebo in preventing CINV resulting from doxorubicin plus cyclophosphamide in early-stage breast cancer patients, especially in the first 24 hours after chemotherapy administration. The short duration of olanzapine was safe and well tolerated.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Dexamethasone; Double-Blind Method; Doxorubicin; Female; Humans; Middle Aged; Nausea; Olanzapine; Ondansetron; Treatment Outcome; Vomiting

Data on the efficacy of olanzapine in patients receiving moderately emetogenic chemotherapy (MEC) are limited. This study aimed to evaluate and compare the efficacy of olanzapine versus placebo in controlling nausea and vomiting in patients receiving MEC.. We conducted a randomized, double-blind, placebo-controlled study to determine whether olanzapine can reduce the frequency of chemotherapy-induced nausea and vomiting (CINV) and improve the quality of life (QOL) in patients receiving palonosetron and dexamethasone as prophylaxis for MEC-induced nausea and vomiting. The primary end point was complete response for the acute phase (0-24 hours after chemotherapy). The secondary end points were complete response for the delayed (24-120 hours) and overall phase (0-120 hours), proportion of significant nausea (visual analogue scale ≥ 25 mm), use ofrescue medications, and effect on QOL.. Fifty-six patients were randomized to the olanzapine (n=29) and placebo (n=27) groups. Complete response rates were not significantly different between the olanzapine and placebo groups in the acute (96.5% vs. 88.0%, p=0.326), delayed (69.0% vs. 48.0%, p=0.118), and overall phases (69.0% vs. 48.0%, p=0.118). However, the percentage of patients with significant nausea (17.2% vs. 44.0%, p=0.032) and the use of rescue medications (0.03±0.19 vs. 1.88±2.88, p=0.002) were lower in the olanzapine group than in the placebo. Furthermore, the olanzapine group demonstrated better QOL (p=0.015).. Olanzapine combined with palonosetron and dexamethasone significantly improved QOL and vomiting control among previously untreated patients receiving MEC, although the efficacy was limited to the reduction of the frequency of CINV.

Topics: Administration, Intravenous; Adult; Aged; Antineoplastic Agents; Dexamethasone; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Nausea; Olanzapine; Palonosetron; Quality of Life; Treatment Outcome

The antipsychotic drug olanzapine is effective against chemotherapy-induced nausea and targets multiple receptors known to be involved in the emetic reflex arch. The drug has a mean half-life of 30 h, which allows for a single daily administration and is therefore of interest in patients with advanced cancer suffering from nausea.. To investigate the antiemetic effect and tolerability of olanzapine in patients with advanced cancer not receiving chemotherapy or irradiation.. Patients with advanced cancer (no curable treatment options) with at least "moderate" nausea and/or one emetic episode within the last 24 h were included if they had not received chemotherapy or irradiation (last 2 weeks) and had no reversible causes of nausea/vomiting. Patients were administered 10 mg olanzapine daily for 5 days (the first day subcutaneously and the following 4 days orally). Nausea, vomiting, and adverse effects were assessed daily for 7 days. The primary efficacy parameter was nausea after 24 h.. Forty patients from four centers were included and all evaluable after 24 h. Thirty-six patients experienced some degree of improvement. The mean two-item N/V score (0-100) at baseline was 66 and improved to 21 and 24 after 24 h and 7 days, respectively. During the course of the study, the dose of olanzapine was reduced in three patients due to adverse events. Five patients were withdrawn from the study primarily due to progression of malignant disease or per patient's request.. Olanzapine appears effective and tolerable as an antiemetic in patients with advanced cancer. Future research should examine a lower dose (5 or 2.5 mg), preferably in a randomized controlled trial.

Topics: Adult; Aged; Antiemetics; Antipsychotic Agents; Female; Humans; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Vomiting

This trial is an open-label, single-arm, multicentre phase II trial. Patients who receive CBDCA (AUC ≥4)-based therapy and have never been administered moderate to high emetogenic chemotherapy will be enrolled. All patients will receive OLZ (5 mg oral administration on days 1-4, after supper) in combination with 5-HT. The study protocol was approved by the institutional review board at each of the participating centres. Data will be presented at international conferences and published in peer-reviewed journals.. UMIN000031646.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Carboplatin; Dexamethasone; Drug Therapy, Combination; Female; Genital Neoplasms, Female; Granisetron; Humans; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Olanzapine; Serotonin 5-HT3 Receptor Antagonists; Treatment Outcome; Vomiting

To explore efficacy of short-course olanzapine with or without low-dose dexamethasone for prevention of delayed emesis in gynecologic cancer patients receiving carboplatin/paclitaxel.. This was a prospective study in 81 chemo-naive patients receiving 0.25 mg intravenous palonosetron, 16 mg dexamethasone, and 10 mg oral olanzapine before chemotherapy. On days 2 and 3, patients randomly received 10 mg olanzapine (arm A; n=27), 10 mg olanzapine plus 4 mg dexamethasone (arm B; n=27), or 8 mg dexamethasone (reference arm C; n=27). The primary endpoint was total control (TC; no vomiting, no rescue antiemetics, and no nausea) on days 2-5, using a diary. Secondary endpoints included proportion of patients with no emesis impact on daily life using the Functional Living Index-Emesis (FLIE) questionnaire, and patient's satisfaction with antiemetic coverage.. Fifty-two percent of patients in arm A (. In this exploratory study with a small sample size, we did not find any clue about better control of delayed emesis with either olanzapine regimen in gynecologic cancer patients treated with carboplatin/paclitaxel and receiving the same prophylaxis for acute emesis.

Topics: Adult; Aged; Carboplatin; Dexamethasone; Drug-Related Side Effects and Adverse Reactions; Female; Genital Neoplasms, Female; Humans; Italy; Middle Aged; Nausea; Olanzapine; Paclitaxel; Palonosetron; Surveys and Questionnaires; Vomiting

The purpose of the study was to compare efficacy and toxicity of olanzapine (OLN; a higher-cost drug) and haloperidol (HAL; a lower-cost drug) in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients who receive highly emetogenic chemotherapy (HEC).. In a randomized, phase II trial, patients were randomly assigned to receive either OLN 10 mg orally on days 1 to 4 or HAL 1 mg orally on day 1 and 0.5 mg twice daily on days 2 to 4. Both groups received ondansetron 16 mg and dexamethasone 12 mg intravenously on day 1. Patients recorded their nausea using the Edmonton Symptom Assessment Scale (ESAS) and recorded daily episodes of vomiting from day 1 to day 5. The primary end point was complete nausea prevention (CNP; ie, ESAS of 0). Secondary end point was complete emesis prevention (CEP).. Sixty-five patients were randomly assigned, and 64 received their allocated treatment (n = 32 in each arm). There was no difference in CNP during the overall period (days 1 to 5) between OLN and HAL (68.7%. In this study, HAL had comparable efficacy to OLN in the management of CINV, which suggests that it is the higher-value option in patients who receive HEC in resource-scarce countries.

Topics: Administration, Intravenous; Administration, Oral; Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Drug Administration Schedule; Female; Haloperidol; Humans; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Ondansetron; Random Allocation; Treatment Outcome; Vomiting; Young Adult

There remains an unmet clinical need for the control of chemotherapy-induced nausea and vomiting (CINV), particularly in the prevention of nausea and the delayed phase control. We evaluated the efficacy and safety of antiemetic therapy with olanzapine, a neurokinin-1 receptor antagonist, a 5-hydroxytryptamine-3 (5-HT. Chemotherapy-naïve patients with lung cancer who received carboplatin-containing chemotherapy were enrolled in this phase-II study. Patients received olanzapine, aprepitant, a 5-HT. Thirty-three patients received olanzapine-containing antiemetic therapy. The overall complete response rate was 93.3% (95% confidence interval, 80.4-98.3%). The frequency of nausea was 15.2% in the delayed phase and 18.2% in the overall phase. Somnolence was observed in 16 patients.. Adding olanzapine to antiemetic therapy with aprepitant, a 5-HT

Topics: Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Carboplatin; Dexamethasone; Drug Therapy, Combination; Female; Humans; Lung Neoplasms; Male; Middle Aged; Nausea; Olanzapine; Prospective Studies; Vomiting

This is an open-label, single-arm, multicentre, phase II trial. Patients who receive CBDCA-based therapies (AUC ≥5) and have never been administered moderate to high emetogenic chemotherapy will be enrolled. All patients will receive a combination of GRN, DEX and OLZ. The primary endpoint is complete response (CR) rate, defined as the absence of emetic episodes and no use of rescue medication for 120 hours after the initiation of CBDCA. Forty-eight patients are required based on our hypothesis that this regimen can improve CR rate from 65% (null hypothesis) to 80% (alternative hypothesis) with a one-sided type I error of 0.1 and a power of 0.8. We set the target sample size at 50 considering dropouts.. The study protocol was approved by the institutional review board at each of the participating centres. Data will be presented at international conferences and published in peer-reviewed journals.. UMIN000031267.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Carboplatin; Female; Humans; Male; Middle Aged; Nausea; Olanzapine; Thoracic Neoplasms; Vomiting; Young Adult

Background To determine the feasibility and efficacy of olanzapine, which is approved by the Pharmaceuticals and Medical Devices Agency as multi acting receptor targeted antipsychotic agent of the thienobenzodiazepine class, for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients undergoing continuous five-day chemotherapy. Patients and methods This study was a prospective dose escalation study at a single center (UMIN ID: UMIN000015386). Patients received a combination of adriamycin and ifosfamide (AI) or a combination of bleomycin, etoposide, and cisplatin (BEP). On days 1-5, all patients received intravenous granisetron (1 mg) and intravenous dexamethasone sodium phosphate (24 mg). Olanzapine was administrated on day-1 to day5 at bedtime. The dose of olanzapine followed a dose-escalation scheme, with monitoring of safety and tolerability at each dose. A 3 + 3 cohort design was used, with three to six patients per cohort. Results Nine patients were enrolled (three for each cohort). No patients experienced dose-limiting toxicity (DLT). The most frequent adverse events were dry mouth and constipation. In each cohort, the maximum severity of nausea was Grade 2, and no patients experienced a vomiting episode. Conclusion A 2.5 mg/day dosage of olanzapine is sufficient to prevent from CINV in Japanese patients receiving continuous five-day chemotherapy. A dose of 10 mg/day, which is recommended by international CINV guidelines, is also tolerated. If CINV is not controlled by an initial dose of 2.5 mg/day of olanzapine, dosage escalation is encouraged. Future studies should compare olanzapine with aprepitant.

Topics: Adult; Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antipsychotic Agents; Bleomycin; Cisplatin; Doxorubicin; Etoposide; Female; Humans; Ifosfamide; Male; Middle Aged; Nausea; Olanzapine; Vomiting; Young Adult

Background The role of olanzapine in the treatment of chemotherapy-induced nausea and vomiting (CINV) in addition to the antiemetic therapeutic combination with aprepitant, setrons, and corticosteroids has not been well defined. Objective To investigate the effectiveness of the addition of olanzapine to a standard triplet therapy for the prevention of CINV in patients who experienced CINV during their first chemotherapy course, despite receiving a well-managed prevention protocol. Setting One comprehensive cancer centre in France. Method In a retrospective study with comparator, patients with a high risk of emesis were assigned to two groups during two different 6-month periods, before and after the introduction of olanzapine in clinical practice, respectively. In the olanzapine group, the antiemetic protocol for the second course of chemotherapy was reinforced by the addition of olanzapine at 5 mg/day from day 1 to 5 in contrast with the control group. Main outcome measure The proportion of patients who experienced neither nausea nor emesis during the delayed phase (24-120 h). Results The 25 patients in each group exhibited comparable characteristics and emetic chemotherapy level. During the first course, no significant difference was observed. During the second course, nausea and vomiting were ameliorated in 12 patients in the olanzapine group and 4 patients in the control group (p < 0.05). Nausea (12 vs. 4, p < 0.05) and vomiting (18 vs. 11, p < 0.05) also significantly improved. In the OLZ group, no adverse event was linked to olanzapine use. Conclusion The addition of olanzapine was observed to effectively restore CINV prevention in patients who did not respond to standard antiemetic therapy.

Topics: Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Drug Resistance; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Nausea; Olanzapine; Retrospective Studies; Serotonin Antagonists; Vomiting; Young Adult

Evidence supports olanzapine for prophylaxis of chemotherapy-induced nausea/vomiting (CINV) for highly emetogenic chemotherapy; however, most studies focus on solid malignancies and single-day regimens. A randomized, double-blinded, placebo-controlled trial was conducted to compare the addition of olanzapine to triplet therapy (fosaprepitant, ondansetron, dexamethasone [FOND-O]) versus triplet therapy alone (FOND) in preventing CINV in hematology patients receiving single-day and multiple-day highly emetogenic chemotherapy and hematopoietic cell transplant (HCT) regimens (NCT02635984). The primary objective of this study was to compare complete response (CR; no emesis and minimal nausea, <25 mm on a 100-mm visual analog scale) during the overall assessment period (chemotherapy days plus 5 days after). Secondary objectives were the number of emesis, number of rescue medications, percent achieving minimal nausea, and percent achieving complete protection (CP; no emesis, rescue antiemetic, or significant nausea), all of which are reported as acute (chemotherapy days), delayed (5 days after chemotherapy), and overall phases. Olanzapine 10 mg or matching placebo were given on each chemotherapy day and 3 days after. Adults with hematologic malignancy receiving HCT regimens of melphalan, BEAM (carmustine, etoposide, cytarabine, melphalan), busulfan (Bu)/cyclophosphamide (Cy), Bu/fludarabine (Flu), Bu/melphalan, FluCy, FluCy-total body irradiation (TBI), etoposide-TBI, and ICE (ifosfamide, carboplatin, etoposide) or 7+3 chemotherapy regimens were included. An estimated 98 patients were required using alpha = .05 and 80% power. No significant differences existed in baseline characteristics between FOND-O (n = 51) and FOND (n = 50) arms. Mean duration of olanzapine was 7.7 days (range, 4 to 11). Discontinuation for possible adverse events occurred in 3 placebo and 0 olanzapine patients. CR was significantly higher for FOND-O in overall (55% versus 26%, P = .003) and delayed (60.8% versus 30%, P = .001) but not acute (P = .13) phases. Significantly more patients receiving FOND-O achieved no more than minimal nausea in overall (P = .001) and delayed phases (P = .0002), as well as fewer overall mean emesis counts (P = .005). CP rates were not different in any assessment phase (P ≥ .05 each). Within the HCT subgroup (n = 64), the CR, CP, and no significant nausea rates were significantly better for FONDO-O in overall and delayed phases (all P < .05). Analysis within th

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Induction Chemotherapy; Male; Melphalan; Middle Aged; Morpholines; Nausea; Olanzapine; Ondansetron; Podophyllotoxin; Vomiting

The Guidelines of the Japan Society of Clinical Oncology recommend standard triple antiemetic therapy with aprepitant, a 5-hydroxytryptamine type 3 receptor antagonist and dexamethasone for patients receiving highly emetogenic chemotherapy. Recently, a Phase III study demonstrated the significance of adding of olanzapine (10 mg) to standard triple antiemetic therapy. Olanzapine is associated with somnolence, and we have previously conducted a randomized Phase II study to evaluate the efficacy and safety of 10 mg and 5 mg olanzapine. Lower dose of olanzapine reduced the incidence of somnolence. Therefore, we conducted a randomized, double blind, placebo-controlled, Phase III study to evaluate the efficacy of olanzapine (5 mg) combined with standard triple antiemetic therapy for cisplatin-based highly emetogenic chemotherapy. This study initiated in Feb 2017. A total of 690 patients are planned to be enrolled over a period of 2 years. This study has been registered at the UMIN Clinical Trials Registry as UMIN000024676.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Benzodiazepines; Cisplatin; Double-Blind Method; Emetics; Female; Humans; Male; Middle Aged; Nausea; Olanzapine; Vomiting; Young Adult

The three-drug combination of a 5-hydroxytryptamine type 3 receptor antagonist, a neurokinin 1 receptor antagonist and dexamethasone is recommended for patients receiving highly emetogenic chemotherapy. However, standard antiemetic therapy is not completely effective in all patients.. We conducted an open-label, single-center, single-arm Phase II study to evaluate the efficacy of olanzapine in combination with standard antiemetic therapy in preventing chemotherapy-induced nausea and vomiting in patients with thoracic malignancy receiving their first cycle of cisplatin-based chemotherapy. Patients received 5 mg oral olanzapine on Days 1-5 in combination with standard antiemetic therapy. The primary endpoint was complete response (no vomiting and no use of rescue therapy) during the overall Phase (0-120 h post-chemotherapy).. Twenty-three men and seven women were enrolled between May and October 2015. The median age was 64 years (range: 36-75 years). The most common chemotherapy regimen was 75 mg/m2 cisplatin and 500 mg/m2 pemetrexed, which was administered to 14 patients. Complete response rates in acute (0-24 h post-chemotherapy), delayed (24-120 h post-chemotherapy) and overall phases were 100%, 83% and 83% (90% confidence interval: 70-92%; 95% confidence interval: 66-93%), respectively. There were no Grade 3 or Grade 4 adverse events. Although four patients (13%) experienced Grade 1 somnolence, no patients discontinued olanzapine.. The addition of 5 mg oral olanzapine to standard antiemetic therapy demonstrates promising efficacy in preventing cisplatin-based chemotherapy-induced nausea and vomiting and an acceptable safety profile in patients with thoracic malignancy.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Cisplatin; Dexamethasone; Female; Humans; Isoquinolines; Male; Middle Aged; Morpholines; Nausea; Olanzapine; Palonosetron; Quinuclidines; Thoracic Neoplasms; Vomiting

Chemotherapy-induced nausea-vomiting (CINV) compromises the quality of life of patients with cancer. We present data on the effectiveness of olanzapine after failure of aprepitant in patients receiving highly emetogenic chemotherapy (HEC). A single-center prospective study was conducted, where patients ≥ 18 years who failed aprepitant, palonosetron, dexamethasone (APD) received olanzapine, palonosetron and dexamethasone (OPD) in the subsequent cycle of HEC. Failure of APD was defined as occurrence of ≥ grade 2 acute and/or delayed nausea ± vomiting. Response rates were compared with what was achieved in their previous cycle with the use of APD in the acute (0-24 h), delayed (24-120 h) and overall (0-120 h) periods after the start of HEC. Impact on life was assessed using the MD Anderson Symptom Inventory (MDASI). Fifty-five patients failed APD and received OPD in the subsequent cycle; 54 were evaluable for response. Complete response rate for OPD versus APD is 80 versus 20% (acute period), 90 versus 18% (delayed period) and 74 versus 5% (overall period), and no nausea rate for OPD versus APD is 57 versus 13% (acute), 59 versus 15% (delayed) and 48 versus 0% (overall period), p < 0.001 for all comparisons. MDASI scores showed significant improvement after switching to OPD. A mild increase in drowsiness noted in patients receiving OPD did not affect daily life in most patients. In patients receiving HEC and failing CINV prophylaxis with APD, switching to OPD regimen in the subsequent cycle greatly improves control of vomiting, increases "no nausea" rates and significantly reduces symptom severity scores.

Topics: Adolescent; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Humans; Middle Aged; Morpholines; Nausea; Olanzapine; Prospective Studies; Treatment Failure; Vomiting; Young Adult

Even with the use of modern antiemetic drugs, chemotherapy-induced nausea and vomiting (CINV) is still a cause of great distress to the patients. Olanzapine, primarily marketed as an antipsychotic, was found to reduce nausea and vomiting in some chemotherapy patients. But it was never tested in Indian population with a diverse genetic background. The present study aims to evaluate the role of olanzapine in CINV in patients receiving platinum-based chemotherapy.. The study was a randomized, controlled, assessor-blinded study on 100 chemotherapy-naïve consenting patients receiving any one from cisplatin, carboplatin or oxaliplatin. The control group (n = 50) received palonosetron and dexamethasone in the approved therapeutic dose from the day 1 of chemotherapy. The test group (n = 50) received additional olanzapine 10 mg/day from day 1 for five consecutive days. CINV and quality of life (QoL) were assessed.. Vomiting was significantly less among the olanzapine-treated patients. Control of delayed emesis was significantly better in this group (complete response among 96 vs. 42 % in the control group, p value <0.0001). Incidence and severity of nausea was significantly less in this group. Failure of anti-CINV measure was 4 % in this group compared to 26 % of the patients of the control group during overall days 1-5. Though sedation was more in these olanzapine-treated patients, there was no dose-limiting adverse event. Quality of life was also better among the olanzapine-treated patients.. Olanzapine was found to be effective as add-on in the control of CINV.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Benzodiazepines; Dexamethasone; Female; Humans; Isoquinolines; Male; Middle Aged; Nausea; Olanzapine; Organoplatinum Compounds; Palonosetron; Quality of Life; Quinuclidines; Vomiting

The primary aim of this study was to compare the effectiveness of olanzapine, palonosetron and ondansetron infusion (standard of care) for the treatment of breakthrough chemotherapy-induced nausea and vomiting (CINV) in patients undergoing hematopoietic stem cell transplantation (HSCT).. It was a randomized open-label prospective study. Sixty-two patients were randomized to receive either ondansetron 32-mg infusion over 24 h, or olanzapine wafer 10 mg once daily in addition to ondansetron 8 mg IV three times a day or a single dose of palonosetron 0.25 mg IV instead of ondansetron. All groups were allowed rescue antiemetics. The primary endpoint was a composite outcome of no emesis, no use of rescue medication, and nausea score reduction of ≥50 %. The secondary endpoint was nausea score reduction of ≥50 %. Both endpoints were measured at 24 and 48 h after initiation of the study treatment. Statistical analysis was conducted using a double-sided Fisher's exact test.. The primary endpoint was achieved in 6, 45, and 18 %, and 6, 64, and 18 % of ondansetron versus olanzapine versus palonosetron patient groups at 24 and 48 h, respectively. The secondary outcome was observed in 17, 60, and 62 %, and 35, 71, and 43 % of ondansetron versus olanzapine versus palonosetron patient groups at 24 and 48 h, respectively. Serious adverse drug reactions were not reported in any arms. Time to engraftment was not significantly different between the arms.. Olanzapine was an effective treatment of breakthrough CINV. A single dose of palonosetron significantly reduced nausea up to 24 h.

Topics: Adolescent; Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Benzodiazepines; Drug-Related Side Effects and Adverse Reactions; Female; Hematopoietic Stem Cell Transplantation; Humans; Isoquinolines; Male; Middle Aged; Nausea; Olanzapine; Ondansetron; Palonosetron; Prospective Studies; Quinuclidines; Transplantation Conditioning; Treatment Outcome; Vomiting; Young Adult

Olanzapine is effective in chemotherapy-induced nausea and vomiting (CINV). In patients receiving highly emetogenic chemotherapy (HEC), its efficacy was reported as rescue therapy for breakthrough emesis refractory to triplet therapy (palonosetron, aprepitant, and dexamethasone). However, its preventive effects with triplet therapy for CINV are unknown. This study aimed to investigate efficacy and safety of preventive use of olanzapine with triplet therapy for CINV of HEC.. This study is a prospective multicenter study conducted by Kansai Clinical Oncology Group. Forty chemo-naïve gynecological cancer patients receiving HEC with cisplatin (≥50 mg/m(2)) were enrolled. Oral olanzapine (5 mg) was administered with triplet therapy a day prior to cisplatin administration and on days 1-5. The primary endpoint was complete response (no vomiting and no rescue) rate for the overall phase (0-120 h post-chemotherapy). Secondary endpoints were complete response rate for acute phase (0-24 h post-chemotherapy) and delayed phase (24-120 h post-chemotherapy) and complete control (no vomiting, no rescue, and no significant nausea) rate and total control (no vomiting, no rescue, and no nausea) rate for each phase. These endpoints were evaluated during the first cycle of chemotherapy.. Complete response rates for acute, delayed, and overall phases were 97.5, 95.0, and 92.5 %, respectively. Complete control rates were 92.5, 87.5, and 82.5 %, respectively. Total control rates were 87.5, 67.5, and 67.5 %, respectively. There were no grade 3 or 4 adverse events.. Preventive use of olanzapine combined with triplet therapy gives better results than those from previously reported studies of triplet therapy.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Benzodiazepines; Cisplatin; Dexamethasone; Female; Genital Neoplasms, Female; Humans; Isoquinolines; Male; Middle Aged; Morpholines; Nausea; Olanzapine; Palonosetron; Prospective Studies; Quinuclidines; Serotonin Antagonists; Vomiting

Despite multiple patient-centered factors being associated with the risk of chemotherapy-induced nausea and vomiting (CINV), these factors are rarely considered when making antiemetic recommendations.. To compare risk model-guided (RMG) antiemetic prophylaxis with physician's choice (PC) in patients receiving chemotherapy for early-stage breast cancer.. A randomized clinical trial of 324 patients with early-stage breast cancer undergoing chemotherapy (cyclophosphamide and an anthracycline) for the first time at 2 specialty cancer care centers in Ottawa from April 10, 2012, to September 2, 2014. Patients were randomized to either the RMG arm (n = 154) or the PC control arm (n = 170). Prior to each cycle of chemotherapy patients in the RMG group were categorized as low or high risk for CINV, and their antiemetic treatments were adjusted accordingly.. Patients considered to be at low risk received standard dexamethasone and a 5-HT3 antagonist, while those at high risk also received aprepitant with or without olanzapine, based on their risk level. The PC control group received antiemetic agents according to the treating physician's discretion.. The primary end points were control of both nausea and vomiting in the acute posttreatment period (first 24 hours after therapy) and in the delayed posttreatment period (days 2-5 after therapy).. The total numbers of chemotherapy cycles delivered in the RMG and PC control groups were 497 and 551 respectively. In the acute period, significantly more patients in the RMG group reported no nausea (53.7% [95% CI, 49.2%-58.1%] vs 41.6% [95% CI, 37.4%-45.3%]; P < .001) and no vomiting (91.8% [95% CI, 89.0%-94.0%] vs 82.2% [95% CI, 78.8%-85.3%]; P < .001) compared with the PC control group. Similarly, significantly more patients in the RMG group reported no nausea (39.6% [95% CI, 35.3%-44.1%] vs 30.7% [95% CI, 26.8%-34.7%]; P = .01) and no vomiting (87.1% [95% CI, 83.8%-90.0%) vs 78.0% [95% CI, 74.3%-81.4%]; P < .001) in the delayed period respectively.. In this trial, the RMG antiemetic prophylaxis led to improved control of acute and delayed CINV compared with physician's choice of therapy.. clinicaltrials.gov Identifier: NCT01913990.

Topics: Adult; Aged; Anthracyclines; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Benzodiazepines; Breast Neoplasms; Choice Behavior; Cyclophosphamide; Decision Support Techniques; Dexamethasone; Drug Administration Schedule; Female; Humans; Middle Aged; Nausea; Neoplasm Staging; Olanzapine; Ondansetron; Ontario; Patient Selection; Practice Patterns, Physicians'; Predictive Value of Tests; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vomiting

To investigate the efficacy and safety of olanzapine in combination with palonosetron and dexamethasone for patients receiving cisplatin (≥50 mg/m(2) ), because this antiemetic therapy has not been sufficiently examined in patients receiving cisplatin.. We conducted a phase II study to evaluate the efficacy and safety of olanzapine in combination with palonosetron and dexamethasone for chemotherapy naïve patients receiving cisplatin (≥50 mg/m(2) ). Patients received prophylactic dexamethasone (20 mg IV, day 1), palonosetron (0.75 mg IV, day 1), and olanzapine (10 mg, days 1-4). The patients were monitored for emesis and nausea for 120 h after chemotherapy. The primary endpoint was the complete response (CR) rate, which was defined as no vomiting episodes and no use of rescue medication for the overall period. CR rates of 65% and 45% would indicate the potential usefulness and the lower limit of interest, respectively.. Fifty-one patients, including 37 esophageal cancer patients were enrolled, of whom 41 (80%) completed the treatment protocol as planned. The complete response rate for the overall period was 43% (95% confidence interval: 29-58); the primary endpoint was not met. Vomiting was frequently observed, with the overall rate of 51%. Most events occurred during 24-72 h after chemotherapy. Somnolence was observed in 73% of the patients, but it was well tolerated in most cases.. Olanzapine combined with palonosetron and dexamethasone did not prevent chemotherapy-induced nausea and vomiting induced by cisplatin as expected. The safety of this antiemetic therapy was confirmed.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Benzodiazepines; Cisplatin; Dexamethasone; Drug Therapy, Combination; Female; Humans; Isoquinolines; Male; Middle Aged; Nausea; Olanzapine; Palonosetron; Quinuclidines; Vomiting

We examined the efficacy of olanzapine for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy.. In a randomized, double-blind, phase 3 trial, we compared olanzapine with placebo, in combination with dexamethasone, aprepitant or fosaprepitant, and a 5-hydroxytryptamine type 3-receptor antagonist, in patients with no previous chemotherapy who were receiving cisplatin (≥70 mg per square meter of body-surface area) or cyclophosphamide-doxorubicin. The doses of the three concomitant drugs administered before and after chemotherapy were similar in the two groups. The two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. Nausea prevention was the primary end point; a complete response (no emesis and no use of rescue medication) was a secondary end point.. In the analysis, we included 380 patients who could be evaluated (192 assigned to olanzapine, and 188 to placebo). The proportion of patients with no chemotherapy-induced nausea was significantly greater with olanzapine than with placebo in the first 24 hours after chemotherapy (74% vs. 45%, P=0.002), the period from 25 to 120 hours after chemotherapy (42% vs. 25%, P=0.002), and the overall 120-hour period (37% vs. 22%, P=0.002). The complete-response rate was also significantly increased with olanzapine during the three periods: 86% versus 65% (P<0.001), 67% versus 52% (P=0.007), and 64% versus 41% (P<0.001), respectively. Although there were no grade 5 toxic effects, some patients receiving olanzapine had increased sedation (severe in 5%) on day 2.. Olanzapine, as compared with placebo, significantly improved nausea prevention, as well as the complete-response rate, among previously untreated patients who were receiving highly emetogenic chemotherapy. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02116530.).

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Intention to Treat Analysis; Male; Middle Aged; Morpholines; Nausea; Olanzapine; Vomiting

A randomized Phase II dose-finding trial comparing olanzapine 10 mg with olanzapine 5 mg for patients receiving highly emetogenic chemotherapy with cisplatin was started in June 2014. The purpose of the trial is to evaluate the efficacy and safety of the two olanzapine doses and to determine which is more promising as a test arm for comparison with the current standard antiemetic care (a combination of aprepitant, a 5-HT3 receptor antagonist and dexamethasone) in a subsequent Phase III trial. Patients receiving cisplatin-containing regimens will be randomized to the olanzapine 10 or 5 mg arm. A total of 150 patients will be accumulated from nine institutions over 2 years. The primary endpoint is complete response defined as no emetic episodes and no use of rescue medications in the delayed (24-120 h) phase. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000014214.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Cisplatin; Dexamethasone; Double-Blind Method; Drug Administration Schedule; Emetics; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Olanzapine; Patient Selection; Research Design; Treatment Outcome; Vomiting

This study evaluated the efficacy of olanzapine in preventing chemotherapy-induced nausea and vomiting (CINV) and improving the quality of life (QoL) of patients with cancer during chemotherapy. Two hundred twenty-nine patients with cancer who received chemotherapy from January 2008 to August 2008 were enrolled, and they were randomised to receive olanzapine or a 5-HT3 receptor antagonist. The patients completed a CINV questionnaire once daily on days 1-5 and a QoL questionnaire on days 0 and 6. The complete response (CR) rates for nausea (76.85% versus 46.2%) and vomiting (84.3% versus 67.6%) were significantly higher in the olanzapine group than in the 5-HT3 receptor antagonist group for delayed CINV but not for acute CINV. The CR rates for nausea (76.85% versus 44.44%) and vomiting (85.95% versus 67.59%) were also significantly higher in the olanzapine group for the 5 days post-chemotherapy. After chemotherapy, global health status, emotional functioning, and insomnia were improved in the olanzapine group but worsened in the 5-HT3 receptor antagonist group, whereas cognitive functioning and appetite loss were unchanged. Moreover, olanzapine significantly improved global health status, emotional functioning, social functioning, fatigue, nausea/vomiting, insomnia, and appetite loss. Olanzapine improved the QoL of patients with cancer during chemotherapy, in part by reducing the incidence of delayed CINV.

Topics: Adolescent; Adult; Aged; Antiemetics; Antineoplastic Agents; Benzodiazepines; Bridged Bicyclo Compounds, Heterocyclic; Female; Humans; Male; Middle Aged; Nausea; Olanzapine; Oxazines; Quality of Life; Serotonin 5-HT3 Receptor Antagonists; Vomiting; Young Adult

The objective of this study is to compare the effectiveness of olanzapine combined with ondansetron or ondansetron alone in preventing chemotherapy-induced nausea and vomiting (CINV) of non-small cell lung cancer (NSCLC). A total of 84 NSCLC patients were equally randomized into intervention group and control group. Both groups were intravenously administered with ondansetron 8 mg 30 min before chemotherapy. In the intervention group, olanzapin 10 mg was orally administered for 8 days, beginning from the first morning of chemotherapy. The antiemetic effectiveness was evaluated in the first chemotherapy cycle. The incidence of acute vomiting was 33.33 % (14/42) and 54.76 % (23/42) in the intervention group and control group (p < 0.05) whereas that of delayed vomiting was 16.57 % (7/42) and 47.62 % (20/42) (p < 0.05). Compared with ondansetron alone, the combination of olanzapine with ondansetron has better effectiveness in preventing CINV in NSCLC patients, particularly for the delayed type.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Benzodiazepines; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Nausea; Olanzapine; Ondansetron; Vomiting

Olanzapine is proved to be effective for chemotherapy induced nausea and vomiting (CINV). But its efficacy in combination with standard antiemetic therapy is unknown. The purpose of this study is to prove the preventive effect of olanzapine for the prevention of CINV caused by highly emetogenic chemotherapy when used with standard antiemetic therapy.. Gynecologic cancer patients receiving cisplatin-based chemotherapy who had grade 2 or 3 nausea in overall phase (0-120 h after chemotherapy) despite standard therapy were assigned to this study. From the next cycles to cycles in which patients developed grade 2 or 3 nausea, they received olanzapine with standard therapy. 5 mg oral olanzapine was administered for 7 days from the day before chemotherapy. The effectiveness of preventive administration of olanzapine was evaluated retrospectively. The primary endpoint was nausea control rate (grade 0 or 1) with olanzapine.. Fifty patients were evaluable. The nausea control rate with olanzapine was improved from 58% to 98% in acute phase (0-24 h after chemotherapy) and 2% to 94% in delayed phase (24-120 h after chemotherapy). In overall phase, the nausea control rate improved from 0% to 92%, and it was statistically significant (P < 0.001).. Preventive use of olanzapine combined with standard antiemetic therapy showed improvement in control of refractory nausea.

Topics: Adult; Aged; Antiemetics; Benzodiazepines; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Nausea; Olanzapine; Treatment Outcome

Chemotherapy-induced nausea and vomiting (CINV) can severely impair patients' quality of life (QOL). Psychotropics, especially olanzapine, have a strong antiemetic effect.. To determine whether olanzapine could reduce the frequency of CINV and improve patients' QOL during chemotherapy.. This was a randomized, double-blind, placebo-controlled trial. Forty-four patients scheduled to receive highly or moderately emetogenic chemotherapy were enrolled. All patients received a 5-hydroxytryptamine3 receptor antagonist, steroid, and neurokinin-1 receptor antagonist. Patients were randomly assigned to take 5 mg/day of oral olanzapine (OL group, n = 22) or placebo (control group, n = 22) daily from the day before chemotherapy (Day 0) to Day 5. The primary endpoint was the rate of patients who achieved total control (no vomiting, no use of rescue medications, and maximum nausea of <5/100mm on a visual analogue scale). The secondary endpoint was Functional Living Index-Emesis questionnaire score on Days 0 and 6.. The rate of patients achieving total control was significantly higher in the OL group (86% and 64% in acute and delayed phases, respectively) than in the control group (55% and 23%, P = 0.045, P = 0.014, respectively). Furthermore, the OL group experienced a better QOL than the control group, as reported on the Functional Living Index-Emesis questionnaire (P = 0.0004).. The addition of 5mg/day of oral olanzapine to standard therapy can reduce the frequency of CINV and improve QOL of patients receiving highly or moderately emetogenic chemotherapy.

Topics: Administration, Oral; Adult; Aged; Antiemetics; Antineoplastic Agents; Benzodiazepines; Double-Blind Method; Eating; Female; Humans; Male; Middle Aged; Nausea; Neurokinin-1 Receptor Antagonists; Olanzapine; Psychotropic Drugs; Quality of Life; Serotonin 5-HT3 Receptor Antagonists; Steroids; Treatment Outcome; Vomiting; Young Adult

To evaluate safety and efficacy of olanzapine for breakthrough emesis in addition to standard antiemetic regimen in cancer patients receiving highly emetogenic chemotherapy.. A phase II prospective open label clinical trial was conducted in tertiary care based hospital. Forty-six cancer patients diagnosed with solid tumors were enrolled to receive at least one cycle of highly emetogenic chemotherapy (HEC) every two to four weeks. Each patient was provided standard antiemetic consisting of the generic form of ondansetron plus corticosteroids and metoclopramide according to clinical practice guideline. Olanzapine was administered as 5 mg orally every 12 hours for two doses in patients experiencing breakthrough emesis for at least one episode despite standard prevention. The efficacy and tolerability were evaluated every six hours for 24 hours (utilizing Index of Nausea, Vomiting and Retching: INVR tool).. Of 46 evaluable patients receiving HEC and additional olanzapine between September 2009 and July 2010, the complete response of breakthrough emesis, retching, and nausea control among patients were 60.9%, 71.7%, and 50.0%, respectively. Adverse events reported were mild and tolerable including dizziness, fatigue, and dyspepsia.. Olanzapine is considered to be safe and effective treatment of breakthrough vomiting in cancer patients undergoing highly emetogenic chemotherapy in the present study.

Topics: Antiemetics; Antineoplastic Agents; Benzodiazepines; Female; Humans; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Prospective Studies; Treatment Outcome; Vomiting

Olanzapine has been shown to be a safe and effective agent for the prevention of chemotherapy-induced nausea and vomiting (CINV). Olanzapine may also be an effective rescue medication for patients who develop breakthrough CINV despite having received guideline-directed CINV prophylaxis.. A double-blind, randomized phase III trial was performed for the treatment of breakthrough CINV in chemotherapy-naive patients receiving highly emetogenic chemotherapy (cisplatin, ≥ 70 mg/m2 or doxorubicin, ≥ 50 mg/m2 and cyclophosphamide, ≥ 600 mg/m2), comparing olanzapine to metoclopramide. Patients who developed breakthrough emesis or nausea despite prophylactic dexamethasone (12 mg IV), palonosetron (0.25 mg IV), and fosaprepitant (150 mg IV) pre-chemotherapy and dexamethasone (8 mg p.o. daily, days 2-4) post-chemotherapy were randomized to receive olanzapine, 10 mg orally daily for 3 days or metoclopramide, 10 mg orally TID for 3 days. Patients were monitored for emesis and nausea for 72 h after taking olanzapine or metoclopramide. Two hundred seventy-six patients (median age 62 years, range 38-79; 43% women; Eastern Cooperative Oncology Group (ECOG) PS 0,1) consented to the protocol. One hundred twelve patients developed breakthrough CINV and 108 were evaluable.. During the 72-h observation period, 39 out of 56 (70%) patients receiving olanzapine had no emesis compared to 16 out of 52 (31%) patients with no emesis for patients receiving metoclopramide (p < 0.01). Patients without nausea (0, scale 0-10, M.D. Anderson Symptom Inventory) during the 72-h observation period were those who took olanzapine, 68% (38 of 56), and metoclopramide, 23% (12 of 52) (p < 0.01). There were no grade 3 or 4 toxicities.. Olanzapine was significantly better than metoclopramide in the control of breakthrough emesis and nausea in patients receiving highly emetogenic chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Cisplatin; Cyclophosphamide; Dexamethasone; Double-Blind Method; Doxorubicin; Female; Humans; Isoquinolines; Male; Metoclopramide; Middle Aged; Morpholines; Nausea; Neoplasms; Olanzapine; Palonosetron; Quinuclidines; Vomiting

To describe the efficacy, safety and tolerability of lurasidone for the acute treatment of schizophrenia using the metrics number needed to treat (NNT) and number needed to harm (NNH).. Study data were pooled from six Phase II and III, 6-week, randomized, placebo-controlled trials that were conducted to test the efficacy and safety of lurasidone for the acute treatment of schizophrenia. Included were the following interventions: fixed doses of lurasidone 20, 40, 80, 120 and 160 mg/d; haloperidol 10 mg/d; olanzapine 15 mg/d; quetiapine extended-release 600 mg/d; placebo. The following outcomes were assessed: responder rates as defined by a reduction of ≥20, 30, 40 or 50% from baseline on the Positive and Negative Syndrome Scale (PANSS) total score; study completion; discontinuation due to an adverse event (AE); weight gain ≥7% from baseline; incidence of spontaneously reported AEs; incidence of total cholesterol ≥240 mg/dL, low-density lipoprotein cholesterol ≥160 mg/dL, fasting triglycerides ≥200 mg/dL and glucose ≥126 mg/dL at endpoint. NNT for the efficacy outcomes were calculated after excluding one failed study. NNH for the safety/tolerability outcomes were calculated using all six studies. Likelihood of being helped or harmed (LHH) was also calculated to illustrate trade-offs between outcomes of improvement ≥30% on the PANSS vs. incidence of akathisia, nausea, sedation, somnolence and parkinsonism.. NNT vs. placebo for PANSS reductions ≥30% were 6, 6, 7 and 4 for lurasidone doses of 40, 80, 120 and 160 mg/d, respectively, and 4 and 3 for olanzapine 15 mg/d and quetiapine extended-release 600 mg/d, respectively. Lurasidone was not associated with any statistically significant disadvantages over placebo for weight gain or metabolic abnormalities; NNH vs. placebo for weight gain ≥7% from baseline was 4 for olanzapine and 9 for quetiapine extended-release in contrast to a NNH for this outcome ranging from 43 to 150 for lurasidone 40-160 mg/d. The 5 most consistently encountered adverse events attributable to lurasidone were akathisia, nausea, sedation, somnolence and parkinsonism, with NNH vs. placebo for lurasidone 40-120 mg/d ranging from 6 (akathisia with 120 mg/d) to 30 (parkinsonism with 80 mg/d). Lurasidone 160 mg/d appeared better tolerated than doses of 40, 80 or 120 mg/d for akathisia, nausea, sedation or somnolence, with no NNH values for these adverse events for 160 mg/d vs. placebo being statistically significant. LHH was favorable for lurasidone when contrasting PANSS reductions vs. adverse events.. NNT and NNH can help quantify efficacy, safety and tolerability outcomes and place lurasidone into clinical perspective. Advantages for lurasidone include a low propensity for weight gain and metabolic abnormalities. More commonly encountered adverse events include akathisia, nausea, sedation, somnolence and parkinsonism, but NNH values are generally in the double digits, reflecting an overall tolerable profile. Individual patient characteristics, values and preferences will need to be considered when selecting lurasidone over other antipsychotics.

Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Blood Glucose; Cholesterol; Dibenzothiazepines; Disorders of Excessive Somnolence; Dose-Response Relationship, Drug; Female; Haloperidol; Humans; Isoindoles; Likelihood Functions; Lurasidone Hydrochloride; Male; Medication Adherence; Nausea; Numbers Needed To Treat; Olanzapine; Psychiatric Status Rating Scales; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Research Design; Schizophrenia; Thiazoles; Treatment Outcome; Triglycerides; Weight Gain

The purpose of the study was to determine the effectiveness of megestrol acetate (MA) and olanzapine (OLN) for the treatment of cancer-related anorexia (CRA).. Eighty adult patients with advanced gastrointestinal cancer or lung cancer (stages III and IV) with CRA (loss of appetite and greater than or equal to 5% loss of preillness stable weight) were randomized to receive daily MA or MA plus OLN for a period of 8 weeks. Patients were assessed weekly using the M.D. Anderson Symptom Inventory with specific measurement of weight, appetite, nausea, and quality of life (QOL) measures.. For the 37 patients receiving MA, 15 patients had a greater than or equal to 5% weight gain, 2 patients had an appetite improvement, 3 patients had an improvement in nausea, and 5 patients had an improvement in QOL at both 4 and 8 weeks. For the 39 patients receiving MA plus OLN, 33 patients had a greater than or equal to 5% weight gain, 25 patients had an appetite improvement, 21 patients had an improvement in nausea, and 23 patients had an improvement in QOL at both 4 and 8 weeks, and there was an improvement in general activity, mood, work, walking, and enjoyment at 8 weeks. There were no grade III or IV treatment-related toxicities in patients receiving MA or the combination of MA plus OLN.. The combination of MA and OLN appears to be an effective intervention for patients with CRA.

Topics: Adult; Aged; Aged, 80 and over; Anorexia; Appetite; Appetite Stimulants; Benzodiazepines; Body Weight; Drug Therapy, Combination; Female; Gastrointestinal Neoplasms; Humans; Lung Neoplasms; Male; Megestrol Acetate; Middle Aged; Nausea; Neoplasm Staging; Olanzapine; Quality of Life; Selective Serotonin Reuptake Inhibitors

This study was designed to mainly evaluate the activity and safety of olanzapine compared with 5-hydroxytryptamine 3(5-HT3) receptor antagonists for prevention of chemotherapy-induced nausea and vomiting(CINV) in patients receiving highly or moderately emetogenic chemotherapy (HEC or MEC). The second goal was to evaluate the impact of olanzapine on quality of life (QoL) of cancer patients during the period of chemotherapy.. 229 patients receiving highly or moderately emetogenic chemotherapy were randomly assigned to the test group [olanzapine(O) 10 mg p.o. plus azasetron (A) 10 mg i.v. and dexamethasone (D) 10 mg i.v. on day 1; O 10 mg once a day on days 2-5] or the control group (A 10 mg i.v. and D 10 mg i.v. on day 1; D 10 mg i.v. once a day on days 2-5). All the patients filled the observation table of CINV once a day on days 1-5, patients were instructed to fill the EORTC QLQ-C30 QoL observation table on day 0 and day 6. The primary endpoint was the complete response (CR) (without nausea and vomiting, no rescue therapy) for the acute period (24 h postchemotherapy), delayed period (days 2-5 postchemotherapy), the whole period (days 1-5 postchemotherapy). The second endpoint was QoL during chemotherapy administration, drug safety and toxicity.. 229 patients were evaluable for efficacy. Compared with control group, complete response for acute nausea and vomiting in test group had no difference (p > 0.05), complete response for delayed nausea and vomiting in patients with highly emetogenic chemotherapy respectively improved 39.21% (69.64% versus 30.43%, p < 0.05), 22.05% (78.57% versus 56.52%, p < 0.05), complete response for delayed nausea and vomiting in patients with moderately emetogenic chemotherapy respectively improved 25.01% (83.07% versus 58.06%, p < 0.05), 13.43% (89.23% versus 75.80%, p < 0.05), complete response for the whole period of nausea and vomiting in patients with highly emetogenic chemotherapy respectively improved 41.38% (69.64% versus 28.26%, p < 0.05), 22.05% (78.57% versus 56.52%, p < 0.05), complete response for the whole period of nausea and vomiting in patients with moderately emetogenic chemotherapy respectively improved 26.62% (83.07% versus 56.45%, p < 0.05), 13.43% (89.23% versus 75.80%, p < 0.05). 214 of 299 patients were evaluable for QoL. Comparing test group with control group in QoL evolution, significant differences were seen in global health status, emotional functioning, social functioning, fatigue, nausea and vomiting, insomnia and appetite loss evolution in favour of the test group (p < 0.01). Both treatments were well tolerated.. Olanzapine can improve the complete response of delayed nausea and vomiting in patients receiving the highly or moderately emetogenic chemotherapy comparing with the standard therapy of antiemesis, as well as improve the QoL of the cancer patients during chemotherapy administration. Olanzapine is a safe and efficient drug for prevention of CINV.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Benzodiazepines; Bridged Bicyclo Compounds, Heterocyclic; Dexamethasone; Female; Humans; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Oxazines; Quality of Life; Serotonin 5-HT3 Receptor Antagonists; Vomiting

The purpose of this study is to determine the control of acute and delayed chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC) and highly emetogenic chemotherapy (HEC) with the combined use of palonosetron and olanzapine, and dexamethasone with the dexamethasone given on day 1 only.. Forty chemotherapy-naive patients received on the day of chemotherapy, day 1, an anti-emetic regimen consisting of dexamethasone, palonosetron, and olanzapine. Patients continued olanzapine for days 2-4 after chemotherapy administration. Patients recorded daily episodes of emesis, daily symptoms utilizing the M.D. Anderson Symptom Inventory, and the utilization of rescue therapy.. For the first cycle of chemotherapy, the complete response (no emesis, no rescue) for the acute period (24 h post-chemotherapy) was 100%, the delayed period (days 2-5 post-chemotherapy) 75%, and the overall period (0 120 h post-chemotherapy) 75% in 8 patients receiving HEC and was 97, 75, and 72% in 32 patients receiving MEC. Patients with no nausea for the acute period was 100%, the delayed period 50%, and the overall period 50% in 8 patients receiving HEC and was 100, 78, and 78% in 32 patients receiving MEC.. The complete response and control of nausea in subsequent cycles of chemotherapy were not significantly different from cycle one.. Olanzapine combined with a single dose of dexamethasone and a single dose of palonosetron was very effective in controlling acute and delayed CINV in patients receiving both HEC and MEC.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Benzodiazepines; Dexamethasone; Female; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Outcome Assessment, Health Care; Palonosetron; Quinuclidines; United States; Vomiting

In a previous phase I study, olanzapine was demonstrated to be a safe and effective agent for the prevention of delayed emesis in chemotherapy-naïve cancer patients receiving cyclophosphamide, doxorubicin, and/or cisplatin. Using the maximum tolerated dose of olanzapine in the phase I trial, a phase II trial was performed for the prevention of chemotherapy-induced nausea and vomiting in chemotherapy-naïve patients. The regimen was 5 mg/day of oral olanzapine on the 2 days prior to chemotherapy, 10 mg on the day of chemotherapy, day 1, (added to intravenous granisetron, 10 mcg/kg and dexamethasone 20 mg), and 10 mg/day on days 2-4 after chemotherapy (added to dexamethasone, 8 mg p.o. BID days 2 and 3, and 4 mg p.o. BID day 4). Thirty patients (median age 58.5 years, range 25-84; 23 women; ECOG PS 0, 1) consented to the protocol, and all were evaluable. Complete response (CR) (no emesis, no rescue) was 100% for the acute period (24 h postchemotherapy), 80% for the delayed period (days 2-5 postchemotherapy), and 80% for the overall period (0-120 h postchemotherapy) in ten patients receiving highly emetogenic chemotherapy (cisplatin > or =70 mg/m(2)). CR was also 100% for the acute period, 85% for the delayed period, and 85% for the overall period in 20 patients receiving moderately emetogenic chemotherapy (doxorubicin > or =50 mg/m(2)). Nausea was very well controlled in the patients receiving highly emetogenic chemotherapy, with no patient having nausea [0 on scale of 0-10, M.D. Anderson Symptom Inventory (MDASI)] in the acute or delayed periods. Nausea was also well controlled in patients receiving moderately emetogenic chemotherapy, with no nausea in 85% of patients in the acute period and 65% in the delayed and overall periods. There were no grade 3 or 4 toxicities and no significant pain, fatigue, disturbed sleep, memory changes, dyspnea, lack of appetite, drowsiness, dry mouth, mood changes, or restlessness experienced by the patients. Complete response and control of nausea in subsequent cycles of chemotherapy (25 patients, cycle 2; 25 patients, cycle 3; 21 patients, cycle 4) were equal to or greater than cycle 1. Olanzapine is safe and highly effective in controlling acute and delayed chemotherapy-induced nausea and vomiting in patients receiving highly and moderately emetogenic chemotherapy.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Antiemetics; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Benzodiazepines; Cisplatin; Cyclophosphamide; Doxorubicin; Female; Humans; Male; Middle Aged; Nausea; Olanzapine; Vomiting

Chemotherapy-induced delayed emesis (DE) can affect up to 50% to 70% of patients receiving moderately and highly emetogenic chemotherapy, although rates are improving. DE most commonly occurs within the first 24 to 48 hours of chemotherapy administration and can persist for 2 to 5 days. Olanzapine, due to its activity at multiple dopaminergic, serotonergic, muscarinic, and histaminic receptor sites, has potential as antiemetic therapy. A phase I study was designed with olanzapine, using a four-cohort dose escalation of 3 to 6 patients per cohort, for the prevention of DE in cancer patients receiving their first cycle of chemotherapy consisting of cyclophosphamide, doxorubicin, platinum, and/or irinotecan. All patients received standard premedication. Olanzapine was administered on days -2 and -1 prior to chemotherapy and continued for 8 days (days 0-7). Episodes of vomiting as well as daily measurements of nausea, sedation, and toxicity were monitored at each dose level. Fifteen patients completed the protocol. No grade 4 toxicities were seen, and three patients experienced a dose-limiting toxicity (grade 3) of a depressed level of consciousness during the study. The maximum tolerated dose appeared to be 5 mg (for days -2 and -1) and 10 mg (for days 0-7). Four of six patients receiving highly emetogenic chemotherapy (cisplatin, > or = 70 mg/m2) and nine of nine patients receiving moderately emetogenic chemotherapy (doxorubicin, > or = 50 mg/m2) had complete control (no vomiting episodes) of DE. Therefore, olanzapine may be an effective agent for the prevention of chemotherapy-induced DE. A phase II trial is underway.

Topics: Adult; Aged; Anorexia; Antiemetics; Antineoplastic Agents; Benzodiazepines; Camptothecin; Cohort Studies; Cyclophosphamide; Dose-Response Relationship, Drug; Doxorubicin; Female; Humans; Irinotecan; Male; Maximum Tolerated Dose; Middle Aged; Mood Disorders; Nausea; Neoplasms; Olanzapine; Organoplatinum Compounds; Time Factors; Treatment Outcome; Vomiting

This post-hoc analysis retrospectively assessed data from two recent studies of antiemetic regimens for chemotherapy-induced nausea and vomiting (CINV). The primary objective was to compare olanzapine-based versus netupitant/palonosetron (NEPA)-based regimens in terms of controlling CINV during cycle 1 of doxorubicin/cyclophosphamide (AC) chemotherapy; secondary objectives were to assess quality of life (QOL) and emesis outcomes over four cycles of AC.. This study included 120 Chinese patients with early-stage breast cancer who were receiving AC; 60 patients received the olanzapine-based antiemetic regimen, whereas 60 patients received the NEPA-based antiemetic regimen. The olanzapine-based regimen comprised aprepitant, ondansetron, dexamethasone, and olanzapine; the NEPA-based regimen comprised NEPA and dexamethasone. Patient outcomes were compared in terms of emesis control and QOL.. During cycle 1 of AC, the olanzapine group exhibited a higher rate of 'no use of rescue therapy' in the acute phase (olanzapine vs NEPA: 96.7% vs 85.0%, P=0.0225). No parameters differed between groups in the delayed phase. The olanzapine group had significantly higher rates of 'no use of rescue therapy' (91.7% vs 76.7%, P=0.0244) and 'no significant nausea' (91.7% vs 78.3%, P=0.0408) in the overall phase. There were no differences in QOL between groups. Multiple cycle assessment revealed that the NEPA group had higher rates of total control in the acute phase (cycles 2 and 4) and the overall phase (cycles 3 and 4).. These results do not conclusively support the superiority of either regimen for patients with breast cancer who are receiving AC.

Topics: Antiemetics; Antineoplastic Agents; Breast Neoplasms; Dexamethasone; Female; Humans; Nausea; Olanzapine; Palonosetron; Quality of Life; Retrospective Studies; Vomiting

Cancer patients often experience symptoms such as anorexia, anxiety and insomnia, which can impact their quality of life. Randomized placebo-controlled trials support prophylactic use of olanzapine for the prevention of nausea and vomiting due to moderate and high-emetic risk chemotherapy. In the setting of palliative care, olanzapine is increasingly utilized as an off-label treatment of symptoms including anorexia-cachexia, anxiety, and insomnia. The following case reports will highlight the potential benefits and risks of off-label olanzapine use for symptom management in cancer patients.. Patient 1 is a female in her 70s with stage IV infiltrating ductal carcinoma of the right breast was having trouble tolerating treatment with letrozole, palbociclib, and denosumab due to uncontrolled nausea resulting in weight loss. Her nausea was refractory to multiple anti-emetics. Low dose olanzapine (2.5 mg) prevented nausea and allowed her to tolerate treatment. Patient 2 is a male in his 50s with renal cell carcinoma, who was receiving treatment with cabozantinib, presented with uncontrolled pain improved with opioid rotation from oxycodone to morphine. He was also experiencing uncontrolled anxiety despite treatment with alprazolam. Alprazolam was weaned and replaced with olanzapine resulting in improvement of his symptoms. Patient 3 is a male in his 60s with pancreatic adenocarcinoma who presented with muscle weakness and fatigue resulting in discontinuation of gemcitabine plus cisplatin. He also had symptoms of depression, poor appetite, and sleep problems. He was prescribed short course of dexamethasone 4 mg by mouth twice daily and olanzapine 5 mg by mouth nightly to improve symptoms. One week after, he presented with confusion and workup revealed hyperammonia which was treated with lactulose, which led to the return of baseline mentation.. Olanzapine antagonizes multiple receptors and has potential to treat a host of symptoms including nausea, anorexia, anxiety, and insomnia, but healthcare providers should be mindful of potential risks and unclear benefits for off-label indications. More research and funding are needed evaluating off-label use of olanzapine for palliation of symptoms in cancer patients who are often frail and susceptible to adverse events.

Topics: Adenocarcinoma; Aged; Alprazolam; Anorexia; Antiemetics; Cisplatin; Female; Humans; Male; Middle Aged; Nausea; Off-Label Use; Olanzapine; Palliative Care; Pancreatic Neoplasms; Quality of Life; Risk Assessment; Sleep Initiation and Maintenance Disorders; Vomiting

Current palliative care guidelines lack a specific treatment algorithm for nausea and emesis. Olanzapine is an atypical antipsychotic with antiemetic activity that's recommended in the guidelines for the treatment of chemotherapy induced nausea and vomiting, but outside of oncologic indications there is a lack of research.. To describe the safety and efficacy of olanzapine for nausea and emesis in the palliative care domain, excluding patients actively undergoing chemotherapy or radiation.. This retrospective chart review encompassed hospitalized adult patients from six hospitals across a large health system admitted from August 2020 through August 2021, with a palliative care consult, and being treated with olanzapine for nausea or emesis. Data was collected on antiemetic therapy affordability, the ability for patients to tolerate medications by mouth, and safety outcomes such as QTc prolongation and increased liver function tests.. A total of 78 patients were included in the study. Olanzapine decreased the number of doses required of antiemetic medications, the median doses of antiemetic medications pre-olanzapine was 1.6 (IQR 0.8-2.8) and post-olanzapine was 0.6 (IQR 0-2.4) (P = 0.0006). After olanzapine was initiated, appetite was improved (P < 0.001), cost of antiemetic therapy was reduced by 65 cents per day (P = 0.059) and olanzapine was prescribed at discharge in 69% of patients. QTc prolongation was observed in 19% of patients, and increased ALT and AST were observed in 4.3% and 0%, respectively.. This retrospective review demonstrated benefit to utilizing olanzapine for nausea and emesis in palliative care patients and should be considered to aid in symptom management.

Topics: Adult; Antiemetics; Antineoplastic Agents; Gastrointestinal Agents; Humans; Long QT Syndrome; Nausea; Olanzapine; Palliative Care; Retrospective Studies; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is common in patients with lymphoma and multiple myeloma (MM) receiving high-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT). Despite a standard triple antiemetic regimen of a neurokinin-1 (NK1) receptor antagonist (RA), a 5-hydroxytryptamine-3 (5-HT3) RA, and dexamethasone is recommended, how to control the protracted CINV in ASCT setting remains an intractable problem. Here, we retrospectively analyze CINV data of 100 patients who received either SEAM (semustine, etoposide, cytarabine, melphalan) or MEL140-200 (high-dose melphalan) before ASCT, evaluate the efficacy and safety of multiple-day administration of fosaprepitant combined with tropisetron and olanzapine (FTO), and compare the results to those of patients who received a standard regimen of aprepitant, tropisetron, and dexamethasone (ATD). The overall rate of complete response (CR), defined as no emesis and no rescue therapy, is 70% in the FTO group compared to 36% in the ATD group. Although CR rates are comparable in the acute phase between the two groups, significantly more patients treated by FTO achieve CR in the delayed phase than those treated by ATD (74% vs. 38%, p < 0.001). Moreover, FTO treatment significantly reduced the percentage of patients who are unable to eat, as well as the requirement for rescue medications. Both regimens are well tolerated and most adverse events (AEs) were generally mild and transient. In conclusion, the antiemetic strategy containing multiple-day administration of fosaprepitant is safe and effective for preventing CINV in lymphoma and MM patients, particularly in the delayed phase.

Topics: Antiemetics; Antineoplastic Agents; Dexamethasone; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma; Melphalan; Morpholines; Multiple Myeloma; Nausea; Olanzapine; Retrospective Studies; Transplantation Conditioning; Transplantation, Autologous; Tropisetron; Vomiting

Olanzapine(OLZ)is a multi-acting receptor-targeted antipsychotic drug approved in Japan in December 2017 for the treatment of anticancer drug-induced nausea and vomiting. However, the recommended doses and administration periods of OLZ in the literature and guidelines are varied. Reports on the efficacy and safety of OLZ combined with perioperative chemotherapy for breast cancer in Japanese patients are few. Moreover, the risk of nausea and vomiting during treatment with anticancer drugs in young and women patients remains to be high. In this study, we conducted an exploratory survey on the optimal duration of OLZ administration(days 1-4: 5 mg, before sleep)during perioperative breast cancer 5-fluorouracil, epirubicin, cyclophosphamide(FEC)therapy. We found that treatment with OLZ showed efficacy in improving nausea grade and maintaining relative dose intensity. Moreover, it could be used safely without interruption due to side effects, such as weight gain, elevation in blood glucose, somnolence, and insomnia. Prophylactic antiemetic therapy with OLZ administration (days 1-4: 5 mg)prior to sleep was effective in patients having FEC therapy-induced nausea and vomiting.

Topics: Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Female; Humans; Nausea; Olanzapine; Vomiting

Olanzapine is an atypical antipsychotic and is widely used for prophylaxis of chemotherapy-induced nausea and vomiting in cancer patients. Previous studies have suggested its potential efficacy for the relief of various symptoms in cancer patients, especially gastrointestinal and psychiatric symptoms. We retrospectively reviewed the prescription of olanzapine to cancer patients at our hospital. Between 2008 and 2020, olanzapine was prescribed to 41 patients for relief of symptoms associated with cancer other than prophylaxis of chemotherapy-induced nausea and vomiting. Of those patients, symptom relief was seen in 53.7%. Notably, olanzapine was effective in 13 of 14 patients with chemotherapy-induced nausea and vomiting refractory to guideline-recommended prophylaxis. Of 16 patients in whom this symptom was not relieved by olanzapine, 13 (81.3%) continued taking olanzapine even after it was judged ineffective. No treatment-related adverse events were seen in this study. Our observation implies good efficacy of olanzapine for refractory chemotherapy-induced nausea and vomiting and a tendency to continue olanzapine even in those for whom it was ineffective.

Topics: Antiemetics; Antineoplastic Agents; Benzodiazepines; Humans; Nausea; Neoplasms; Olanzapine; Retrospective Studies; Vomiting

For the past 5 years, most major antiemesis guidelines have included olanzapine-containing regimens among the recommended options for prophylaxis with highly emetogenic chemotherapy (HEC). We analyzed the uptake of olanzapine in clinical practice and the changing composition of multidrug antiemetic regimens.. A retrospective analysis was performed using an OptumLabs deidentified database of medical and pharmacy claims, which was filtered for patients starting HEC in the interval of 2006 to Q2 of 2021. Descriptive statistics were used to analyze patient characteristics and year-by-year antiemetic prescribing patterns, coinciding with cycles 1 and 2 of chemotherapy.. A total of 63,154 distinct patients were included. The median age was 58 years (range, 18-88). Breast (45.2%) and hematologic (20.8%) cancers were the most common diagnoses. In 2016, olanzapine was prescribed to 1.4% of patients with cycle 1 of HEC. Prescriptions increased modestly each year, and by 2021, 13.9% of patients received olanzapine with their first cycle of chemotherapy. An additional 5.7% of patients received olanzapine for breakthrough symptoms or enhanced prophylaxis during cycle 2. In 2021, more than three-quarters of patients were prescribed antiemetics in a guideline-concordant manner, with an olanzapine-containing quadruplet (12.2%), an NK1-receptor antagonist triplet (64.5%), or an olanzapine triplet (suppressed for small sample size).. Despite inclusion in major antiemesis guidelines, there has been relatively slow uptake of olanzapine for prophylaxis with HEC. This finding highlights the challenges of disseminating information and keeping prescribing systems updated with the newest evidence in supportive oncology.

Topics: Antiemetics; Antineoplastic Agents; Humans; Middle Aged; Nausea; Olanzapine; Retrospective Studies; Vomiting

Topics: Adolescent; Antiemetics; Child; Gastrointestinal Agents; Humans; Nausea; Neoplasms; Olanzapine; Vomiting

Olanzapine-containing regimens have been reported to be effective in preventing CINV following highly emetogenic chemotherapy (HEC), but it is unsure whether it is cost-effective. There has been no cost-effectiveness analysis conducted for olanzapine using costs from the USA. The aim of this study is to determine whether olanzapine-containing antiemetic regimens are cost-effective in patients receiving HEC.. A decision tree model was constructed to evaluate the cost and health outcomes associated with olanzapine-containing antiemetic regimens and otherwise-identical regimens. One-way sensitivity analyses were conducted to individually investigate the effect of (i) lower complete response (CR) rates of olanzapine, closer to non-olanzapine-containing regimens; (ii) higher FLIE scores for patients who achieved no/incomplete response, closer to FLIE scores of patients achieving a complete response; (iii) differing costs of olanzapine to reflect different costs per hospitals, globally, due to different insurance systems and drug costs; and (iv) varying costs for uncontrolled CINV, to account for varying durations of chemotherapy and accompanying uncontrolled CINV.. Olanzapine regimens have an expected cost of $325.24, compared with $551.23 for non-olanzapine regimens. Meanwhile, olanzapine regimens have an expected utility/index of 0.89, relative to 0.87 for non-olanzapine regimens. Olanzapine-containing regimens dominate non-olanzapine-containing regimens even if CR of olanzapine-containing regimens fall to 0.63. Only when CR is between 0.60 and 0.62 is olanzapine both more effective and more costly.. Olanzapine-containing regimens are both cheaper and more effective in the prophylaxis of CINV in HEC patients, compared with non-olanzapine-containing regimens. Future CINV trial resources should be allocated to understand newer antiemetics and compare them to olanzapine-containing regimens as the control arm. Further analysis should use nationally representative data to examine medication costs by payer type.

Topics: Antiemetics; Cost-Benefit Analysis; Female; Humans; Male; Nausea; Olanzapine; Vomiting

Domperidone, ondansetron and olanzapine can prolong the QT interval. The clinical use of combinations of these drugs is not uncommon. Our study aimed to determine the presence of any QTc prolonging effect of the combination when used as antiemetic in patients receiving cancer chemotherapy. We carried out a prospective, observational study of patients with malignancy who were to receive domperidone, ondansetron and olanzapine-containing antiemetic regimen. Electrocardiograms were recorded before and during the administration of antiemetics, for three consecutive days. A blinded assessor determined the QTc interval using Bazett and Fridericia formulae. Thirty-six patients completed the study; 23 (63.9%) were females. There was a statistically significant change in QTc with time (Fridericia, χ

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Domperidone; Drug Combinations; Electrocardiography; Female; Humans; Long QT Syndrome; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Ondansetron; Prospective Studies; Single-Blind Method; Young Adult

Olanzapine 10 mg is recommended for breakthrough chemotherapy-induced nausea and vomiting. However, there is a possibility that 5 mg can be expected to be sufficiently effective. We aimed to investigate the efficacy and safety of olanzapine 5 mg for breakthrough chemotherapy-induced nausea and vomiting.. A single-arm prospective trial of olanzapine 5 mg every 24 h for 72 h was conducted to treat breakthrough chemotherapy-induced nausea and vomiting in patients receiving carboplatinbased chemotherapy. The primary endpoint was total control (i.e., no emesis, no nausea, and no rescue medications) over 72 h. The secondary endpoints were early efficacy using the nausea scores at 30, 60, and 120 min after taking olanzapine from baseline and adverse events.. Among 84 potentially eligible patients, 19 patients who took olanzapine for breakthrough chemotherapy-induced nausea and vomiting were examined. The total control rate was 32% (95% CI: 13- 57%), 65% (95% CI: 38-89%), 65% (95% CI: 38-89%), and 29% (95% CI: 10-56%) during 2-24, 24-48, 48-72 h, and overall period, respectively. The nausea scale significantly reduced after 30 min (P=0.0078), and the scale had been reduced by 67% from the baseline after 60 min. The adverse event of somnolence of any grade was observed in 13 (68%) patients, 6 (32%) of whom had grade 2 and 1 (5%) grade 3 somnolence.. Olanzapine 5 mg did not show the expected effect on the complete disappearance of breakthrough chemotherapy-induced nausea and vomiting within 24 h.

Topics: Antiemetics; Antineoplastic Agents; Benzodiazepines; Carboplatin; Humans; Nausea; Olanzapine; Prospective Studies; Vomiting

To examine the safety, effectiveness, and patient-perceived benefit of treatment with olanzapine for nausea and vomiting (N/V) in patients with advanced cancer.. We conducted a multicenter prospective observational study in a tertiary care setting (Trial registration number: UMIN000020493, date of registration: 2016/1/12). We measured the following: average nausea in the last 24 h using a Numeric Rating Scale (NRS: range 0-10) at baseline and day 2, patient-perceived treatment benefit (based on a 5-point verbal scale), and adverse events (AEs; using the Common Terminology Criteria for Adverse Events version 4).. The 85 participants (45% men) had a mean age of 58.7±15.8 years. Major causes of N/V were opioids (44%) and chemotherapy (34%). All patients received a daily dose of olanzapine of 5 mg or less as first-line treatment (N=35) or second- or later-line treatment (N=50). Nausea NRS decreased from 6.1±2.2 to 1.8±2.0 (differences: -4.3, 95% CI -3.7 to -4.9, p<0.001). The proportion of patients who did not experience vomiting episodes in the last 24 h increased from 40-89%. Mean decrease in nausea NRS by patient-perceived treatment benefit were as follows: -0.8 for "none" (n=4, 5%); -2.8 for "slight" (n=17, 20%); -3.3 for "moderate" (n=14, 16%); -4.7 for "lots" (n=25, 29%); and -6.1 for "complete" (n=25, 29%; p-for-trend<0.001). The most prevalent AE was somnolence (n=15, 18%).. Short-term and relatively low-dose olanzapine treatment was effective for multifactorial N/V. Confirmatory studies with longer observation periods are needed to clarify the duration of the effect and adverse events.

Topics: Adult; Aged; Antiemetics; Female; Humans; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Palliative Care; Referral and Consultation; Vomiting

Nausea and vomiting are consistently identified among the most distressing side effects of chemotherapy. In recent years, Olanzapine (OLZ) treatment was added to anti-emetic guidelines as a treatment for chemotherapy-induced nausea and vomiting (CINV), despite little available data supporting a mechanism behind the positive benefits of the drug. Here, we examine whether OLZ reduces cisplatin chemotherapy-induced side effects on food intake and pica behavior in rats (i.e., kaolin intake, a proxy for nausea/emesis). Behavioral experiments tested whether systemic or hindbrain administration of OLZ ameliorated cisplatin-induced pica, anorexia, and body weight loss in rats. We also tested whether systemic OLZ reduces cisplatin-induced neuronal activation in the dorsal vagal complex (DVC), a hindbrain region controlling emesis. Lastly, given their role in regulating feeding and emesis, circulating ghrelin levels and central mRNA expression levels of serotonin (HT) receptor subunits, including 5-HT2C, were measured in brain regions that regulate CINV and energy balance in an exploratory analysis to investigate potential mediators of OLZ action. Our results show that both systemic and hindbrain administration of OLZ attenuated cisplatin-induced kaolin intake and body weight loss, but not anorexia. Systemic OLZ decreased cisplatin-induced c-Fos immunofluorescence in the DVC and prevented cisplatin-induced reductions in circulating ghrelin levels. IP OLZ also blocked cisplatin-induced increases in

Topics: Animals; Antiemetics; Antineoplastic Agents; Cisplatin; Nausea; Olanzapine; Rats; Vomiting

Olanzapine is effective for schizophrenia management; however, it is contraindicated in diabetes patients. In addition, olanzapine is useful for treating nausea and vomiting, such as in the case of chemotherapy-induced nausea and vomiting (CINV). Therefore, we hypothesized that the contraindicated prescription of olanzapine likely occurs among cancer patients with diabetes, especially by non-psychiatric physicians. Hence, we conducted a nationwide survey to elucidate the situation of such contraindicated prescriptions and the associated risk factors. We extracted the data of patients who were newly prescribed olanzapine between April 2015 and March 2017 from the health insurance claims database developed by JMDC, Inc., Tokyo. The patients who were prescribed contraindicated olanzapine were defined as those who were prescribed olanzapine after a diagnosis of diabetes and diabetes drug prescription. In all, the data of 7181 patients were analyzed. We evaluated the proportion of diabetes patients who were prescribed contraindicated olanzapine from among those who were prescribed olanzapine. Furthermore, we investigated the background of patients who were prescribed olanzapine for information such as olanzapine prescribers and history of cancer chemotherapy. In all, 100 diabetes patients (1.39%) were prescribed olanzapine. In these patients, the frequency of olanzapine prescription was higher by non-psychiatry/neurology physicians than by psychiatry/neurology physicians (3.25 and 0.85%, respectively). Additionally, all olanzapine prescriptions in cancer chemotherapy-treated diabetes patients were issued by non-psychiatry/neurology physicians. Thus, our study revealed there were diabetes patients who were prescribed olanzapine. Additionally, olanzapine for CINV management was more likely to be a contraindicated prescription.

Topics: Adult; Antiemetics; Antineoplastic Agents; Antipsychotic Agents; Contraindications, Drug; Databases, Factual; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Japan; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Risk Factors; Schizophrenia; Vomiting

The use and availability of cannabis for recreational and medical purposes has become more widespread with increased legalization. Adverse health outcomes of this increased use include cannabinoid hyperemesis syndrome (CHS), which is underrecognized in medical settings. Cessation of substance use is the recommendation of choice for the complete resolution of CHS. However, interventions that provide rapid relief may be necessary in treatment-refractory cases. Little evidence is available to guide care in these cases. Here we report 4 cases of treatment-refractory CHS, all of which remitted after treatment with olanzapine. Olanzapine is known to block multiple neurotransmitter receptors involved in nausea and vomiting in chemotherapy-induced nausea and vomiting. Outcomes of the cases reported here suggest that off-label use of olanzapine may be effective in the symptomatic treatment of refractory CHS and may be the preferred treatment in cases in which comorbid psychotic symptoms or agitation are present.

Topics: Cannabinoids; Humans; Marijuana Abuse; Nausea; Olanzapine; Vomiting

Chemotherapy-induced nausea and vomiting occurs in up to 80% of patients undergoing chemotherapy treatment and is associated with a deterioration in quality of life. Olanzapine is an atypical antipsychotic antagonist blocking a variety of neurotransmitters in the nausea and vomiting pathophysiology.. The primary objective of this study is to determine whether olanzapine is associated with improved breakthrough nausea and vomiting in patients undergoing hematopoietic stem cell transplant. Secondary outcomes include number of documented emesis episodes, an evaluation of patient oral intake, and number of rescue antiemetic agents administered after olanzapine initiation.. This is a retrospective cohort review examining the effects of olanzapine for the treatment of breakthrough nausea and vomiting following hematopoietic stem cell transplant. Patients undergoing autologous or allogeneic hematopoietic stem cell transplant between January 2014 and October 2017 were included.. A total of 150 patients were included in the study. Olanzapine use was associated with a complete response in 30% of patients for breakthrough chemotherapy-induced nausea and vomiting (p < 0.0001). An improvement in nausea (p < 0.0001) and vomiting (p = 0.02) was also observed in patients. Olanzapine administration was associated with lower as needed antiemetic usage (p < 0.0001) as well as fewer emesis episodes (p < 0.0001) but had no effect on oral intake (p = 0.13).. Olanzapine was associated with significant improvements in breakthrough nausea and vomiting control while reducing the number of emesis episodes and required antiemetic doses in the hematopoietic stem cell transplant population. Olanzapine may be beneficial in optimizing antiemetic regimens for breakthrough chemotherapy-induced nausea and vomiting control in patients undergoing hematopoietic stem cell transplant.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Nausea; Olanzapine; Retrospective Studies; Vomiting

Topics: Antineoplastic Agents; Humans; Nausea; Olanzapine; Vomiting

Topics: Antiemetics; Humans; Male; Metoclopramide; Nausea; Neoplasms; Olanzapine; Vomiting

Topics: Antiemetics; Antineoplastic Agents; Cisplatin; Double-Blind Method; Humans; Nausea; Olanzapine; Vomiting

Topics: Antiemetics; Antineoplastic Agents; Cisplatin; Double-Blind Method; Humans; Nausea; Olanzapine; Vomiting

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Female; Humans; India; Middle Aged; Nausea; Olanzapine; Uterine Cervical Neoplasms; Vomiting; Young Adult

Topics: Antiemetics; Antineoplastic Agents; Benzodiazepines; Humans; Nausea; Olanzapine; Vomiting

Topics: Antiemetics; Humans; Nausea; Olanzapine; Vomiting

Topics: Antiemetics; Double-Blind Method; Humans; Metoclopramide; Nausea; Neoplasms; Olanzapine; Vomiting

Topics: Humans; Nausea; Neoplasms; Olanzapine

The efficacy of olanzapine (mean dose 0.09 mg/kg/dose) was evaluated in 31 children 2-18 years of age, for chemotherapy induced breakthrough vomiting. Among 42 chemotherapy blocks with emesis, complete and partial responses were observed in 34 (80.9%) and 6 (14.3%) blocks, respectively, while 1/31(2.4%) patient had refractory vomiting. Mild sedation and transient transaminitis were the observed side effects.

Topics: Antiemetics; Antineoplastic Agents; Child; Humans; Nausea; Neoplasms; Olanzapine; Vomiting

Recent studies suggested that olanzapine, together with dexamethasone and serotonin-3 receptor antagonist (5HT3RA), is effective in preventing chemotherapy-induced nausea and vomiting (CINV) following highly emetogenic chemotherapy (HEC). This regimen is particularly useful in Southeast Asia (SEA) countries where resources are limited. We aimed to evaluate the cost-effectiveness of incorporating olanzapine into standard antiemetic regimens for the prevention of CINV in patients receiving HEC among SEA countries.. Using a decision tree model, clinical and economic outcomes associated with olanzapine-containing regimen and standard antiemetic regimen (doublet antiemetic regimen: dexamethasone+first generation 5HT3RA) in most SEA countries except in Singapore (triplet antiemetic regimen: dexamethasone+first generation 5HT3RA + aprepitant) for CINV prevention following HEC were evaluated. This analysis was performed in Thailand, Malaysia, Indonesia, and Singapore, using societal perspective method with 5-day time horizon. Input parameters were derived from literature, network meta-analysis, government documents, and hospital databases. Outcomes were incremental cost-effectiveness ratio (ICER) in USD/quality-adjusted life year (QALY) gained. A series of sensitivity analyses including probabilistic sensitivity analysis were also performed.. Compared to doublet antiemetic regimen, addition of olanzapine resulted in incremental QALY of 0.0022-0.0026 with cost saving of USD 2.98, USD 27.71, and USD 52.20 in Thailand, Malaysia, and Indonesia, respectively. Compared to triplet antiemetic regimen, switching aprepitant to olanzapine yields additional 0.0005 QALY with cost saving of USD 60.91 in Singapore. The probability of being cost-effective at a cost-effectiveness threshold of 1 GDP/capita varies from 14.7 to 85.2% across countries.. The use of olanzapine as part of standard antiemetic regimen is cost-effective for the prevention of CINV in patients receiving HEC in multiple SEA countries.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Asia, Southeastern; Cost-Benefit Analysis; Dexamethasone; Drug Therapy, Combination; Emetics; Humans; Indonesia; Malaysia; Nausea; Olanzapine; Quality-Adjusted Life Years; Serotonin 5-HT3 Receptor Antagonists; Singapore; Vomiting

Topics: Adolescent; Adolescent Psychiatry; Antiemetics; Antineoplastic Agents; Child; Humans; Nausea; Olanzapine

Topics: Adolescent; Adolescent Psychiatry; Antineoplastic Agents; Child; Humans; Nausea; Olanzapine; Vomiting

Olanzapine is commonly utilized in palliative care for the treatment of nausea, and a known side effect of olanzapine is increased appetite. Olanzapine is also known to cause re-emergence of eating disorders (EDs) in patients utilizing olanzapine for its antipsychotic effects. It is unclear to what extent this may also occur in patients with serious/life-limiting illness.. We present a case of a 70-year-old female with recurrent ovarian cancer and a history of bulimia nervosa (BN) that developed resurgence of her BN after initiation of olanzapine for cancer-associated nausea. Her BN resolved with reducing the dose of olanzapine.. It is important to recognize that recurrence of EDs can occur when using olanzapine in the palliative care setting.

Topics: Aged; Antineoplastic Agents; Antipsychotic Agents; Appetite; Bulimia Nervosa; Female; Humans; Nausea; Olanzapine; Ovarian Neoplasms; Palliative Care; Treatment Outcome

The prevalence of nausea/vomiting in patients with advanced cancer has a wide range. Due to a very low level of evidence regarding antiemetic treatment, current guidelines recommend an etiology-based approach. The evidence for this approach is also slim and research is urgently needed.. (Part One) to elucidate the prevalence of nausea and the possible associations with sociodemographic and clinical variables and (Part Two) to investigate possible etiologies of nausea and antiemetic treatments initiated in patients with nausea.. Patients with advanced cancer and no recent antineoplastic treatment were included in a prospective two-part study. In Part One, patients completed an extended version of the EORTC QLQ-C15-PAL. Nauseated patients could then be included in Part Two in which possible etiologies and antiemetic treatment were recorded and a follow-up questionnaire was completed.. Eight hundred twenty-one patients were included and 46% reported any degree of nausea. Younger age and female sex were associated with a higher degree of nausea. Common etiologies included constipation, opioid use, and "other," and treatments associated with a statistically significant decrease in nausea/vomiting were olanzapine, laxatives, corticosteroids, domperidone, and metoclopramide.. Nausea was a common symptom in this patient population and many different etiologies were suggested. Most patients reported a lower degree of nausea at follow-up. More research in treatment approaches and specific antiemetics is strongly needed.

Topics: Adrenal Cortex Hormones; Adult; Age Factors; Aged; Aged, 80 and over; Antiemetics; Female; Humans; Male; Metoclopramide; Middle Aged; Nausea; Neoplasms; Olanzapine; Prevalence; Prospective Studies; Sex Factors; Surveys and Questionnaires; Vomiting

There are no prospective pediatric trials evaluating olanzapine for chemotherapy-induced nausea and vomiting (CINV) prevention.. This study evaluated the feasibility of a trial of olanzapine to evaluate the contribution of olanzapine to CINV control in pediatric oncology patients.. Patients < 18 years receiving CINV prophylaxis with ondansetron/granisetron/palonosetron ± dexamethasone ± aprepitant were eligible to participate in this prospective, single-arm, open-label study. All patients received olanzapine (0.14 mg/kg/dose; max 10 mg/dose) once daily orally starting before the first chemotherapy dose and continuing for up to four doses after the last chemotherapy administration. A future trial was considered feasible if mean time to enroll 15 patients was ≤ 12 months/site, ≥ 12/15 took at least half of the planned olanzapine doses, and ≤ 3/15 experienced significant sedation or dizziness despite dose reduction. The proportion of children who experienced complete CINV control (no nausea, vomiting, or retching) was described.. Fifteen patients (range 4.1-17.4 years) participated; mean recruitment period was 9.3 months/site. All patients took at least half of the planned olanzapine doses. Six patients experienced sedation which resolved with olanzapine dose reduction (N = 5) or bedtime administration (N = 1). Olanzapine was stopped in one patient with blurry vision and in another with increased plasma GGT values. In both the acute and delayed phases, eight patients experienced complete control of vomiting but almost all (14/15) had nausea.. A pediatric trial of olanzapine for CINV control is feasible. Our findings will inform the design of a future study.

Topics: Adolescent; Antiemetics; Child; Child, Preschool; Feasibility Studies; Female; Humans; Male; Nausea; Olanzapine; Vomiting

Topics: Antineoplastic Agents; Aprepitant; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Nausea; Olanzapine; Retrospective Studies; Transplantation, Autologous; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is one of most distressing adverse events during cancer chemotherapy. In breast cancer patients receiving anthracycline and cyclophosphamide (AC) chemotherapy, CINV is poorly controlled.. The prevalence of guideline-consistent antiemetic medication and control of CINV were investigated retrospectively in breast cancer patients receiving the first cycle of AC chemotherapy. Risks for CINV were analyzed by the multivariate logistic regression analysis. The effect of olanzapine added to the standard antiemetic medication on the incidence of CINV was subsequently evaluated in separate patients who received the first cycle of AC chemotherapy.. Although the guideline-consistent antiemetic medication was performed in all subjects, the control rate of nausea (32%), but not vomiting (78%) was low. Risk analysis indicated that age younger than 55-year-old was a significant factor that reduces the control of both nausea and vomiting. Olanzapine (5 mg/day for 5 days), when added to the standard three-drug antiemetic medication, significantly improved the control of nausea and complete response.. CINV was poorly controlled in breast cancer patients receiving AC chemotherapy, in which age younger than 55-year-old was a significant risk for both nausea and vomiting. Olanzapine was effective for improvement of the control of CINV associated with AC chemotherapy. Therefore, care should be taken to prevent CINV in young patients receiving AC chemotherapy by adding olanzapine to the standard three-drug antiemetic medication.

Topics: Age Factors; Anthracyclines; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Benzodiazepines; Breast Neoplasms; Cyclophosphamide; Female; Humans; Middle Aged; Nausea; Olanzapine; Retrospective Studies; Vomiting

Topics: Adolescent; Antiemetics; Antineoplastic Agents; Child; Child, Preschool; Female; Humans; Infant; Male; Nausea; Olanzapine

Olanzapine is an atypical antipsychotic that has shown efficacy for the treatment of nausea, anxiety, and insomnia. This study was conducted to evaluate the efficacy of olanzapine (5 mg) combined with 5-HT3 receptor antagonists and dexamethasone for the prevention of chemotherapy-induced nausea and vomiting (CINV) in lung patients receiving cisplatin-based (25 mg/m2 d1-3) highly emetogenic chemotherapy (HEC).Olanzapine (5 mg) was administered a day prior to cisplatin administration and continued on days 1 to 5. We evaluated complete response (CR) rate and rates of no nausea and no vomiting in 3 periods. In addition, Self-Rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), and The Functional Living Index-Emesis (FLIE) questionnaire were also assessed.A total of 40 lung cancer patients were included. CR for acute, delayed, and over all phases were 82.5%, 75.0%, and 70.0%, respectively. The rate of no nausea in the acute phase was 70.0% and 62.5% in delayed phase. The rate of no vomiting in the acute phase was 85.0%, and 77.5% in delayed phase. The rate of no nausea and no vomiting in the overall phase were 57.5% and 75.0%, respectively. The median SAS and SDS score were 37.9 and 41.6 in pre-chemotherapy, respectively. Up to day 6 after chemotherapy treatment, the median SAS and SDS score were 36.9 and 42.0, respectively. The median FLIE score was 111.7. The main side effects were grade 1 somnolence (35.0%) and mild constipation (52.5%).Around 5 mg olanzapine may be used as a potential, safe, and cost-beneficial alternative to prevent nausea and vomiting for HEC, particular for multiday chemotherapy regimen.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Anxiety; Benzodiazepines; Cisplatin; Depression; Dexamethasone; Drug Therapy, Combination; Female; Humans; Lung Neoplasms; Male; Middle Aged; Nausea; Olanzapine; Ondansetron; Treatment Outcome; Vomiting; Young Adult

Chemotherapy-induced nausea and vomiting (CINV) is a distressing adverse effect. Neurokinin-1 receptor antagonist (NK1RA)-containing regimens are the standard regimens for CINV prophylaxis in patients with cancer receiving highly or moderately emetogenic chemotherapy (HEC or MEC). NK1RA agents are expensive and were not registered in Sudan. Recently, regimens containing olanzapine, the available and affordable medication in Sudan, were introduced as another option. This study aimed to compare the efficacy of an olanzapine-containing regimen with the antiemetic regimen that was currently used in our institute for CINV prophylaxis in HEC/MEC settings.. The study prospectively compared an olanzapine-containing regimen (acute phase: olanzapine, ondansetron, dexamethasone; delayed phase: olanzapine, ondansetron) with an ondansetron/dexamethasone regimen (acute phase: ondansetron, dexamethasone; delayed phase: ondansetron) in adult patients with cancer receiving HEC or MEC. The study outcomes were complete response (CR; no emesis and no rescue medications) and nausea control (no nausea), which were assessed in the acute (0 to 24 hours), delayed (24 to 120 hours), and overall (0 to 120 hours) phases.. The study included 131 patients (olanzapine-containing: 50 patients; ondansetron/dexamethasone: 81 patients). CR and nausea control were higher in the olanzapine-containing than in the ondansetron/dexamethasone regimen (CR: acute phase, 86% v 71.6%; P = .086; delayed phase, 72% v 30.9%; P < .001; overall phase, 66% v 25.9%; P < .001; nausea control: acute phase, 86% v 74.1%; P = .127; delayed phase, 76% v 34.6%; P < .001; overall phase, 72% v 29.6%; P < .001). The major toxicity of olanzapine was grade 1 and 2 sedation or drowsiness (25 patients).. An olanzapine-containing regimen has better efficacy for prevention of CINV in the HEC/MEC setting. Oncologists working in a limited-resource setting should be familiar with olanzapine-containing regimens, because NK1RA agents are not affordable and not easily available.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Humans; Middle Aged; Nausea; Neoplasms; Olanzapine; Ondansetron; Receptors, Neurokinin-1; Sudan; Vomiting; Young Adult

This study aimed to compare the antiemetic efficacy and safety of a four-drug combination with those of a standard three-drug combination in Japanese patients with breast cancer treated with anthracycline. We retrospectively analyzed data from Japanese patients with breast cancer, who had received their first cycle of anthracycline and were treated with aprepitant, palonosetron, and dexamethasone with or without olanzapine. This retrospective observational study was performed at Ehime University Hospital using the electronic medical records. Multivariable and propensity score-adjusted analyses were performed to compare the onset of complete response (CR) failure between the groups. One-hundred and thirty patients were included in this study and the four- and three-drug group had 22 and 108 patients, respectively. Similar to multivariable logistic regression analysis, propensity-adjusted logistic regression analysis revealed that the four-drug group was markedly associated with a decreased odds of CR failure in the overall, acute, and delayed phases (odds ratio [OR]: 0.27, 95% confidence interval [CI]: 0.10-0.73; OR: 0.28, 95% CI: 0.10-0.76; and OR: 0.15, 95% CI: 0.04-0.57, respectively). Additionally, treatment-related adverse events were well tolerated in both the groups. These findings suggest that the antiemetic efficacy of the four-drug combination is superior to that of the standard three-drug combination.

Topics: Anthracyclines; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Dexamethasone; Drug Therapy, Combination; Female; Humans; Incidence; Middle Aged; Nausea; Olanzapine; Palonosetron; Retrospective Studies; Sleep Initiation and Maintenance Disorders; Sleepiness; Treatment Outcome; Vomiting

Topics: Adult; Advance Care Planning; Aged; Antiemetics; Baclofen; Benzodiazepines; Constipation; Depressive Disorder, Major; Dyspnea; Female; Hiccup; Humans; Male; Methylphenidate; Middle Aged; Morphinans; Morphine; Nausea; Olanzapine; Palliative Medicine; Polyethylene Glycols; Prochlorperazine; Pruritus; Sertraline; Terminal Care; Walkers

Acute and delayed chemotherapy-induced nausea and vomiting (CINV) occurs in most patients who receive high-dose melphalan and significantly affects patients' quality of life during autologous stem cell transplantation. Faced with unsatisfactory results using an aprepitant-based regimen, an olanzapine-based regimen was initiated, with the hope of improving the incidence of acute and delayed CINV. A retrospective study was conducted to compare the effectiveness of olanzapine- versus aprepitant-based regimens for CINV prevention in adult hematopoietic stem cell recipients who received high-dose melphalan.. We compared olanzapine (n = 43) to aprepitant (n = 54) and fosaprepitant (n = 20). Olanzapine was given orally at 5 mg twice daily for 5 days, aprepitant was given at 125 mg on day -1 and 80 mg on days 0 and 1, and fosaprepitant was given at 150 mg on day -1. The dose of 2 concomitant drugs (dexamethasone and 5-hydroxytryptamine type 3 receptor antagonist) was similar in the 2 groups. Nausea prevention was the primary endpoint. A complete response using a composite index of no emesis and no use of rescue medications was the secondary endpoint.. The results showed that olanzapine significantly reduced the number of patients who experienced acute (P < .0001) or delayed (P < .004) nausea and significantly reduced the use of rescue medications for acute-onset (P < .0046) and delayed-onset (P < .0001) CINV compared with aprepitant.. Compared with fosaprepitant, olanzapine reduced the number of patients with acute (P < .0318) and delayed (P < .1519) nausea and reduced the need for rescue medications for acute-onset (P < .0643) and delayed-onset (P < .0024) CINV.

Topics: Adult; Aged; Algorithms; Antiemetics; Aprepitant; Benzodiazepines; Disease Management; Female; Hematopoietic Stem Cell Transplantation; Humans; Induction Chemotherapy; Male; Melphalan; Middle Aged; Morpholines; Multiple Myeloma; Myeloablative Agonists; Nausea; Olanzapine; Transplantation Conditioning; Treatment Outcome; Vomiting

Olanzapine is an atypical antipsychotic indicated for the treatment of schizophrenia and known to be effective in the management of delirium. In addition to its use for these indications olanzapine has also been used in the management of chemotherapy induced nausea and vomiting and otherwise difficult to control nausea and vomiting in palliative care settings. Although considered to be well tolerated with a lower incidence of extrapyramidal effects than first generation antipsychotics there are a small number of reports of olanzapine inducing delirium. Reported here are two cases of "probable" acute cognitive impairment following treatment of nausea with olanzapine. The cognitive impairment associated with olanzapine is probably mediated through its activity at cholinergic receptors a known risk factor for delirium particularly in the elderly.

Topics: Acute Disease; Aged; Antiemetics; Benzodiazepines; Delirium; Humans; Male; Nausea; Olanzapine

Cisplatin is commonly used for esophageal and gastric cancer, but has a high emetic risk. Although the control of vomiting is favorable, nausea is still poorly controlled in patients receiving cisplatin-based regimens. The present study was designed to determine the risks for cisplatin-induced nausea. The effect of olanzapine, an antipsychotic drug, as an antiemetic for patients with risk of poor control of nausea was subsequently examined.. The prevalence of antiemetic medication and the control of nausea and vomiting were retrospectively examined in patients with esophageal or gastric cancer receiving the first cycle of cisplatin-based chemotherapy. Risks for nausea were analyzed by multivariate logistic regression analysis, in which threshold for age and cisplatin dose wer assessed by receiver operating characteristic curve analysis.. A total of 186 patients received cisplatin-based regimens during January 2011 and December 2016. Guideline-consistent antiemetic medication was administered to all patients. Although the rate of no vomiting was high (93%), the rate of non-significant (grade 2 or more) nausea was insufficient (64%) during the overall period. Risk analysis showed that cisplatin dose of 50 mg/m. Being female and cisplatin doses at 50 mg/m

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Benzodiazepines; Cisplatin; Dose-Response Relationship, Drug; Esophageal Neoplasms; Female; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Nausea; Olanzapine; Retrospective Studies; Risk Factors; Sex Factors; Stomach Neoplasms

Nausea and vomiting are distressing and relatively common symptoms in palliative care populations. Adequate control may be difficult to achieve, requiring multiple agents. Although a growing literature supports the use of olanzapine in management of chemotherapy induced nausea and vomiting, the published literature in palliative care populations is less extensive.. The study objective was to assess the efficacy of olanzapine in the management of difficult to control nausea and vomiting in a palliative care patient population.. Patients whose nausea and vomiting had not responded adequately to other antiemetics were treated with olanzapine 5mg as a single dose at night. Treatment was considered to be successful if the patient reported an adequate improvement in their symptoms. Duration of observed treatment ranged from three days to five months.. Sixteen patients were treated with an evaluable outcome in 14. Of these, 13 reported a self-evaluated adequate ongoing improvement in their symptoms. One patient experienced no relief and one other experienced a return of nausea after two weeks; this patient requested a change of treatment due to unacceptable sedative effects. There were no other reports of significant adverse events.. Olanzapine provided adequate, ongoing relief of nausea and vomiting with an acceptable adverse effect profile in 13 of 14 evaluable patients. Particularly in comparison with metoclopramide and haloperidol, olanzapine should be considered for first-line therapy for nausea and vomiting in this population. Further evaluation of dose ranging and safety is required.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Australia; Benzodiazepines; Female; Humans; Male; Middle Aged; Nausea; Olanzapine; Palliative Care; Treatment Outcome; Vomiting

Nausea and vomiting are among the most common and distressing symptoms in patients with advanced cancer. Olanzapine, an antipsychotic agent, is known to have an affinity for multiple neurotransmitter receptors. Previous studies have reported olanzapine to be efficacious in the treatment of nausea and vomiting. Although it has been administered at a number of facilities, its applicability to treat nausea and vomiting in patients with advanced cancer is poorly understood. We investigated the use of olanzapine for nausea and vomiting in patients with advanced cancer at multiple centers. This retrospective study was carried out at seven palliative care units and three facilities with palliative care teams in Japan from 2013 to 2015. The dosage of olanzapine, treatment duration, and duration from initial use until death were collected from the medical records. One hundred and eight patients met our inclusion criteria. The average dose of olanzapine was 3.6 mg (2.5 mg, n = 61; 5 mg, n = 46; 10 mg, n = 1) and average treatment duration was 18.7 days. The average duration from initial use until death was 39.0 days. There were no differences in the duration of administration until death between olanzapine doses (2.5 and 5 mg). Our results suggest that olanzapine have been used in patients with poor prognoses for nausea and vomiting in patients with advanced cancer. Conducting a prospective trial would further yield promising results.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Antipsychotic Agents; Benzodiazepines; Female; Humans; Japan; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Palliative Care; Patient Comfort; Retrospective Studies; Surveys and Questionnaires; Vomiting

Triplet antiemetic therapy with neurokinin 1 receptor blocker, 5-hydroxytryptamine receptor blocker and steroids is commonly used in patients who are highly emetic after chemotherapy. However, an alternative antiemetic therapy for patients who are resistant to triplet antiemetic therapy is not established. Olanzapine is recommended in the guidelines as an optional antiemetic drug. However, the effectiveness of adding olanzapine to triplet antiemetic therapy is unknown. In this study, the effectiveness and safety of adding olanzapine to triplet antiemetic therapy with aprepitant, palonosetron and dexamethasone as highly emetic anthracycline-containing adjuvant chemotherapy for primary breast cancer patients were prospectively investigated.. Forty-five patients with breast cancer who experienced >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/day) was administered orally from the first day of chemotherapy for 4 days, and the number of episodes of vomiting, scale of nausea, dietary intake and somnolence were compared with the symptoms after the first cycle.. As the primary endpoint, the nausea grade was significantly improved by adding olanzapine (P < 0.05). As the secondary endpoints, mean nausea scale (3.2→1.9, Day 1; 3→1.3-1, Days 2-6) and dietary intake (33.6→53.8%, Day 1; 42.0→60.7-78.1%, Days 2-6) were improved by adding olanzapine. Only four patients withdrew due to somnolence and/or dizziness.. This study demonstrated the effectiveness and tolerability of adding low-dose olanzapine for patients with insufficient nausea relief with triplet antiemetic therapy consisting of palonosetron, steroid and aprepitant.

Topics: Administration, Oral; Adult; Aged; Anthracyclines; Antiemetics; Antineoplastic Agents; Benzodiazepines; Breast Neoplasms; Chemotherapy, Adjuvant; Drug Resistance, Neoplasm; Drug Therapy, Combination; Female; Humans; Middle Aged; Nausea; Olanzapine; Severity of Illness Index; Vomiting

While the efficacy of olanzapine in the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) has been documented, the literature on the use of olanzapine as a rescue medication for breakthrough CINV has been scarce. The following study retrospectively evaluated the safety and efficacy of olanzapine for the treatment of breakthrough CINV. The efficacy and safety of olanzapine in the prophylactic setting was also examined in a smaller cohort.. Electronic medical records of adult patients aged >17 years receiving a prescription for olanzapine from the Odette Cancer Centre Pharmacy at Sunnybrook Hospital between January 2013 and June 2015 were reviewed retrospectively. Inclusion criteria required receiving one or more doses of olanzapine for the rescue or prophylaxis of CINV and documentation of the outcome.. A total of 154 patients and 193 treatment cycles were included in the breakthrough setting, while a total of 16 patients and 20 treatment cycles were included in the prophylaxis setting. In the breakthrough setting, 88% of cases experienced improved nausea, while 21% of cases reported improved vomiting. In the prophylactic setting, 100% of cases experienced improved nausea, while 65% achieved improved vomiting. A total of 43% of cases in the breakthrough setting and 65% of cases in the prophylactic setting experienced sedation.. Olanzapine is effective in improving CINV in both the prophylactic and breakthrough settings. The safety, efficacy, and appropriate dosage of olanzapine for the rescue of breakthrough CINV should be prospectively evaluated in a randomized controlled trial (RCT).

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Benzodiazepines; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Retrospective Studies; Treatment Outcome; Vomiting; Young Adult

Topics: Antiemetics; Antipsychotic Agents; Anxiety; Benzodiazepines; Cachexia; Delirium; Humans; Nausea; Olanzapine; Sleep Initiation and Maintenance Disorders; Vomiting

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Dexamethasone; Drug Therapy, Combination; Female; Humans; Middle Aged; Morpholines; Nausea; Olanzapine; Ondansetron; Vomiting

We investigated the effects of olanzapine on cisplatin-induced pica (the consumption of non-nutrient materials such as kaolin) and glucose homeostasis in rats to clarify the effects of olanzapine when used as an anti-emetic drug. Rats were injected intraperitoneally (i.p.) with either 5 mg/kg cisplatin or saline. Additionally, 2 or 10 mg/kg olanzapine were administered i.p. to the rats 10 min before the administration of cisplatin and subsequently administered every 24 h for 3 d. Kaolin and food intake was measured using an automatic monitoring apparatus. Plasma glucose levels were measured by an enzyme electrode method. The plasma levels of insulin and intact proinsulin were measured by enzyme-linked immunosorbent assay (ELISA). The proinsulin-to-insulin (P/I) ratio was calculated. Cisplatin significantly increased kaolin intake, but decreased food intake and body weight up to 72 h. Olanzapine had no effect on these parameters. Neither olanzapine nor cisplatin alone had a significant effect on the plasma levels of glucose, insulin, or proinsulin. However, a combination of olanzapine and cisplatin significantly decreased plasma insulin levels, but increased plasma intact proinsulin levels and the P/I ratio. Our results suggest that an additive deterioration of insulin-secreting beta-cell function and disturbance of glucose homeostasis should be considered during treatment of patients with olanzapine for cisplatin-induced nausea and vomiting.

Topics: Animals; Antiemetics; Antineoplastic Agents; Benzodiazepines; Blood Glucose; Cisplatin; Eating; Homeostasis; Kaolin; Male; Nausea; Olanzapine; Pica; Proinsulin; Rats, Wistar; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. The use of a combination of a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist, dexamethasone, and a neurokinin-1 (NK-1) receptor antagonist has significantly improved the control of acute and delayed emesis in single-day chemotherapy. The first generation 5-HT3 receptor antagonists have been very effective in the control of chemotherapy induced emesis in the first 24 h postchemotherapy (acute emesis), but have not been as effective against delayed emesis (24-120 h postchemotherapy). Palonosetron, a second generation 5-HT3 receptor antagonist with a different half-life, a different binding capacity, and a different mechanism of action than the first generation 5-HT3 receptor antagonists appears to be the most effective agent in its class. Despite the control of emesis, nausea has not been well controlled by current agents. Olanzapine, a FDA approved antipsychotic that blocks multiple neurotransmitters: dopamine at D1, D2, D3, D4 brain receptors, serotonin at 5-HT2a, 5-HT2c, 5-HT3, 5-HT6 receptors, catecholamines at alpha1 adrenergic receptors, acetylcholine at muscarinic receptors, and histamine at H1 receptors, has emerged in recent trials as an effective preventative agent for chemotherapy-induced emesis and nausea, as well as a very effective agent for the treatment of breakthrough emesis and nausea. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.

Topics: Antiemetics; Antineoplastic Agents; Benzodiazepines; Dexamethasone; Half-Life; Humans; Isoquinolines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Olanzapine; Palonosetron; Quality of Life; Quinuclidines; Receptors, Neurokinin-1; Receptors, Serotonin, 5-HT3; Serotonin 5-HT3 Receptor Antagonists; Vomiting

Here we present a case of successful treatment employing a mixed approach including pharmacological and psychosomatic treatments for a 72-year-old woman who experienced severe nausea and vomiting in reaction to postoperative stress from gastric cancer surgery. This case demonstrates that appropriate provision of psychosomatic treatments, including a psychotherapeutic session and autogenic training, enhances the efficacy of pharmacotherapy.

Topics: Aged; Amoxapine; Anti-Anxiety Agents; Antidepressive Agents; Antiemetics; Benzodiazepines; Bromazepam; Clomipramine; Combined Modality Therapy; Female; Humans; Mianserin; Mirtazapine; Nausea; Olanzapine; Physical Therapy Modalities; Postoperative Complications; Psychotherapy; Stomach Neoplasms; Stress, Psychological; Vomiting

Antiemetics are being used both for the treatment and prophylaxis of opioid-induced nausea and vomiting (OINV) in clinical practice, despite the lack of evidence for the prophylactic benefit. Data regarding the actual status of prophylactic antiemetic use for OINV remain to be elucidated.. The objective of this study was to evaluate the practice among Japanese physicians of the prophylactic use of antiemetics when starting opioids prescription for the prevention of opioid-induced nausea and vomiting.. This questionnaire survey was targeted among physicians experienced in cancer pain treatment at two institutions of Japan (Nagoya University Hospital and Ichinomiya City Municipal Hospital). The questionnaire assessed the physicians' practice and beliefs regarding the prophylactic antiemetics prescription when they start opioids in patients with cancer pain.. Questionnaires were filled in and received from 112 physicians from two institutions. Eighty-two percent of physicians prescribed prophylactic antiemetics at the beginning of opioid prescription, and the most commonly prescribed drug for this purpose was prochlorperazine (88%).. Despite the lack of evidence, Japanese physicians commonly prescribe prophylactic antiemetics, most commonly prochlorperazine, for OINV. Prospective clinical trials are necessary to evaluate the efficacy of this practice.

Topics: Analgesics, Opioid; Antiemetics; Benzodiazepines; Chemoprevention; Domperidone; Health Care Surveys; Humans; Japan; Metoclopramide; Nausea; Neoplasms; Olanzapine; Pain; Practice Patterns, Physicians'; Prochlorperazine; Steroids; Vomiting

The role of olanzapine added to a dopamine antagonist and benzodiazepine for the treatment of refractory chemotherapy-induced nausea and vomiting (CINV) is incompletely characterized in all levels of chemotherapy emetogenicity. This retrospective study evaluated the efficacy of the addition of olanzapine in adults experiencing refractory CINV stratified by chemotherapy emetogenicity.. Thirty-three adults who experienced CINV refractory to guideline-recommended prophylaxis and breakthrough antiemetics (dopamine antagonists and benzodiazepines) and received at least one dose of olanzapine 5-10 mg per os were evaluated. Failure was defined as >5 emesis events in 24 h or more than 10 cumulative doses of rescue antiemetics following first olanzapine dose per treatment cycle. Post hoc analyses investigated variables impacting olanzapine efficacy.. The addition of olanzapine demonstrated an overall success rate of 70 %. This success rate did not differ between chemotherapy regimens of high versus low-to-moderate emetogenicity (p = 0.79), prophylaxis with serotonin antagonist plus corticosteroid and aprepitant versus serotonin antagonist alone (p = 0.77), or age over 50 versus ≤50 years (p > 0.99). A trend toward greater benefit was seen in women (p = 0.08).. The addition of olanzapine to a dopamine antagonist and benzodiazepine demonstrated high efficacy rates for refractory CINV irrespective of chemotherapy emetogenicity. The high success rates among all groups suggests that incomplete resolution of CINV with prophylactic serotonin antagonists and breakthrough dopamine antagonists plus benzodiazepine may benefit from the addition of olanzapine regardless of gender, degree of chemotherapy emetogenicity, number of prophylactic antiemetics, or age. The trend toward greater control of emesis in women merits further investigation.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Benzodiazepines; Dopamine Antagonists; Female; Humans; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Retrospective Studies; Vomiting; Young Adult

Topics: Aged; Aged, 80 and over; Antiemetics; Antipsychotic Agents; Benzodiazepines; Female; Humans; Male; Middle Aged; Nausea; Olanzapine; Palliative Care; Retrospective Studies; Vomiting

This study aims to investigate the effects of low-dose olanzapine on preventing occurrence and controlling the severity of nausea and vomiting related to duloxetine in treating major depressive disorder.. Two hundred sixty-eight subjects with major depressive disorder were divided into control and trial groups. The control group had 165 subjects and was treated with duloxetine only, whereas the trial group had 103 subjects and received duloxetine combined with low-dose olanzapine. After the treatment for 2 weeks, both groups were evaluated for occurrence and severity of adverse effects on digestive tract using the Treatment Emergent Symptom Scale.. The trial group, scored at 13, showed significantly less occurrence and severity of nausea and vomiting than the control group, scored at 38 (P < 0.05). The occurrence of nausea and vomiting in the trial group is significantly lower compared with that in the control group, and the occurrence decreases as the dose of olanzapine increases (P < 0.05). The antiemetic effect of olanzapine is valid to all subjects who received it.. Duloxetine combined with low-dose olanzapine can effectively reduce the occurrence and severity of duloxetine-related nausea and vomiting. With the increase of olanzapine dose, the antiemetic effect becomes stronger. Olanzapine is a safe and efficient drug for the prevention of duloxetine-related nausea and vomiting.

Topics: Adolescent; Adult; Antidepressive Agents; Antiemetics; Benzodiazepines; Depressive Disorder, Major; Drug Administration Schedule; Drug Therapy, Combination; Duloxetine Hydrochloride; Female; Humans; Male; Middle Aged; Nausea; Olanzapine; Thiophenes; Treatment Outcome; Vomiting; Young Adult

Bowel obstruction is one of the most common complications in patients with advanced cancer. Incomplete bowel obstruction is one of the leading causes of nausea and vomiting, which may result in a substantial impairment to quality of life. We explored the antiemetic activity of olanzapine against nausea and vomiting in cancer patients with incomplete bowel obstruction. This retrospective study was carried out on a palliative care unit, using an electronic medical record from 2007 to 2009. The intensity of the symptom was evaluated and classified from the medical records on four scales. The frequency of vomiting also was noted from the medical records. During this study period, 20 patients met the inclusion criteria. The average dose of olanzapine was 4.9±1.2mg and treatment duration was 23.4±16.2 days. Olanzapine treatment led to a significant decrease in the average intensity score of nausea from 2.4±0.7 to 0.2±0.4 (P<0.001). Of the 20 patients, 18 (90%) experienced a reduction in the intensity of nausea. The average frequency of vomiting significantly decreased after olanzapine treatment from 1.1±1.3 times/day (median 0.5; range 0-4) before the treatment to 0.3±0.5 times/day (median 0; range 0-1) after the treatment (P<0.01). Before the treatment, 10 patients experienced vomiting; eight of these patients experienced a decrease in the frequency of vomiting with olanzapine treatment. Our study suggests the potential efficacy of olanzapine for relief of nausea in incomplete bowel obstruction. A prospective trial is promising.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Benzodiazepines; Female; Humans; Intestinal Obstruction; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Retrospective Studies; Treatment Outcome; Vomiting

Topics: Adult; Antidepressive Agents; Benzodiazepines; Cyclopropanes; Depression; Drug Therapy, Combination; Female; Humans; Milnacipran; Nausea; Obsessive-Compulsive Disorder; Olanzapine; Selective Serotonin Reuptake Inhibitors

Mirtazapine and olanzapine are easy-to-use psychiatric drugs with potent antinausea effects. Ondansetron and later members of the 'setron class are currently standard treatments for cancer chemotherapy-related nausea and emesis. They are potent 5-HT3 blockers, but it is often not appreciated that mirtazapine and olanzapine bind with similar affinity to 5-HT3 receptors, have a longer half-life, are considerably cheaper than the 'setron class, and often offer better and smoother 24-h nausea control than 'setron class drugs. Mirtazapine and olanzapine often have salutary antianxiety effects and improve sleep quality. They occasionally relieve chemotherapy-related and advanced cancer-related nausea and appetite decrease better than the 'setron group that are specifically marketed for nausea control. Mirtazapine and olanzapine frequently give potent nausea reduction and appetite increase in advanced cancer-related cachexia. Several cytokine changes potentially induced by mirtazapine and olanzapine use are discussed that may have salutary effects in several cancers. We suggest mirtazapine and olanzapine be included as first-line options in treating both chemotherapy- and advanced cancer-related nausea. Multiple clinical and economic advantages of mirtazapine and olanzapine over currently used 'setron class medicines are reviewed. Double-blind studies against the 'setron class drugs are warranted.

Topics: Antiemetics; Antineoplastic Agents; Benzodiazepines; Cachexia; Humans; Mianserin; Mirtazapine; Nausea; Neoplasms; Olanzapine; Ondansetron; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists

Topics: Antiemetics; Benzodiazepines; Delirium; Humans; Lung Neoplasms; Male; Middle Aged; Nausea; Olanzapine; Palliative Care; Terminal Care; Treatment Outcome

Topics: Antiemetics; Benzodiazepines; Delirium; Humans; Lung Neoplasms; Male; Middle Aged; Nausea; Olanzapine; Palliative Care; Terminal Care

Nausea and vomiting are difficult symptoms to manage in patients with advanced cancer. Several classes of antiemetics are available, including phenothiazines, butyrophenones, substituted benzamides and selective serotonin antagonists, as well as corticosteroids. Most patients will respond to either single agents or combinations that frequently include corticosteroids. A minority of patients will have nausea that fails to respond. The atypical antipsychotic, olanzapine, relieves nausea in some patients failing to respond to the usual antiemetics. Two case reports are presented and the rationale for olanzapine's benefit is discussed.

Topics: Adult; Aged; Antiemetics; Benzodiazepines; Breast Neoplasms; Female; Humans; Lung Neoplasms; Nausea; Olanzapine; Pirenzepine; Vomiting

Nausea is a common problem among palliative care patients, which is often undertreated. Olanzapine, an atypical antipsychotic, possesses a unique neurotransmitter binding profile that is similar to methotrimeprazine, an anti-emetic widely used in Europe for recalcitrant nausea. We report a case series of six patients who suffered nausea which was resistant to initial treatment with traditional antiemetics; each patient exhibited marked improvement when treated with olanzapine.

Topics: Aged; Antiemetics; Benzodiazepines; Female; Humans; Male; Middle Aged; Nausea; Olanzapine; Palliative Care; Pirenzepine; Treatment Outcome; United States

This open-label pilot study explored the antiemetic activity of olanzapine, an atypical antipsychotic, in patients with advanced cancer requiring opioid analgesics for pain. Fifteen patients received 2 days of a washout and placebo "run-in" followed by two day periods on each of three doses of olanzapine (2.5 mgs, 5 mgs, and 10 mgs). Patients completed a daily food journal as well as the Mini Mental State Exam, Simpson Angus Scale, Barnes Akathisia Scale, and the Functional Assessment of Cancer Therapy-General across four time periods, with special attention being placed on the nausea item. Eleven women and 4 men with varied primary cancer sites participated. The average age of the sample was 58 years (SD = 16.8). All three dose levels were associated with significant reductions in nausea compared to baseline. Diary entries recorded by the subjects suggested substantial benefits to overall well being and the 5mg condition was associated with statistically significant improvement in overall quality of life over baseline (F = 12.0, p < 0.005). No extrapyramidal symptoms were noted and mental status exams were not changed over the course of the eight days. These results suggest an antiemetic effect for olanzapine and indicate the need for a controlled trial.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Benzodiazepines; Dyskinesia, Drug-Induced; Female; Humans; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Pain; Palliative Care; Pilot Projects; Pirenzepine