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Introduction: Olanzapine administered at a 10mg dosage for prophylaxis of chemotherapy-induced nausea and vomiting may be associated with fatigue, drowsiness and reduced general activity. Therefore, a 5mg dose may be preferred, to reduce the occurrence of adverse events. The aim of this study was to conduct a network meta-analysis, and report on the efficacy of olanzapine administered at 5mg, relative to when administered at 10 mg. Methods: We used previously-published data from the systematic review by Chow et al which identified 17 adult trials which used 10mg doses, 3 which used 5mg doses, and 1 which used a mix of 5 and 10mg doses. A multivariate network meta-analysis using a restricted maximum likelihood model was used. Results: The complete response rate in the acute phase is not statistically different, between 5mg and 10mg doses of olanzapine – RR 0.97, 95% CI: 0.83 – 1.13. Additionally, in the overall phase, 5mg olanzapine is similarly as efficacious as 10mg olanzapine – RR 0.95, 95% CI: 0.56 – 1.60. Evaluation of data demonstrated that there was inadequate information to compare the toxicities of the two doses. Conclusion: Our analyses support individual published trials, and the rationale for future trials to compare 5mg to 10mg olanzapine regimens in head-to-head comparisons.

Chemotherapy-induced nausea and vomiting (CINV) continues to be a common side effect of systemic anticancer therapy, decreasing quality of life and increasing resource utilization. The aim of this meta-analysis was to investigate the comparative efficacy and safety of palonosetron relative to other 5-HT3RAs. A literature search was carried out in Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. Full-text references were then screened and included in this meta-analysis if they were an RCT and had adequate data regarding one of the five primary endpoints—complete response (CR), complete control (CC), no emesis, no nausea, or no rescue medications. A total of 24 RCTs were included in this review. Palonosetron was statistically superior to other 5-HT3RAs for 10 of the 19 assessed endpoints. Only one endpoint—emesis in the overall phase—had noticeable more favorable data for palonosetron to the point that it approached the 10% risk difference (RD) threshold as specified by the MASCC/ESMO antiemetic panel; another two endpoints (CR in the overall phase and nausea in the delayed phase) approached the 10% threshold. Palonosetron seems to be more efficacious and safe than other 5-HT3RAs—statistically superior in 10 of 19 endpoints. It is, however, only clinically significant in one endpoint and approached clinically significant difference in another two endpoints. Within the limits of this meta-analysis, our results indicate that palonosetron may not be as superior in efficacy and safety as reported in a previous meta-analysis, and supports the recent MASCC/ESMO, ASCO, and NCCN guidelines in not generally indicating palonosetron as the 5-HT3RA of choice.

PURPOSE: This review summarizes the recommendations for the prophylaxis of acute and delayed nausea and vomiting induced by multiple-day chemotherapy, high-dose chemotherapy, and breakthrough nausea and vomiting as agreed at the MASCC/ESMO Antiemetic Guidelines update meeting in Copenhagen in June 2015.METHODS: A systematic literature search using PubMed from January 01, 2009 through January 06, 2015 with a restriction to papers in English was conducted.RESULTS: There were three phase III randomized trials in patients undergoing high-dose chemotherapy and stem cell transplant and eight single arm non-randomized clinical studies (single in patients undergoing transplantation and one in patients receiving multiple-day chemotherapy treatment). We used a total of two randomized clinical trials in this guideline update. For patients receiving treatment for breakthrough chemotherapy-induced nausea and vomiting, a phase III randomized trial investigating the use of olanzapine versus metoclopramide in patients receiving highly emetogenic chemotherapy and a second single arm study looking at the effectiveness of olanzapine were identified.CONCLUSIONS: It was concluded that for patients receiving high-dose chemotherapy with stem cell transplant, a combination of a 5-HT3 receptor antagonist with dexamethasone and aprepitant (125 mg orally on day 1 and 80 mg orally on days 2 to 4) is recommended before chemotherapy. For patients undergoing multiple-day chemotherapy-induced nausea and vomiting, a 5-HT3 receptor antagonist, dexamethasone, and aprepitant, are recommended before chemotherapy for the prophylaxis of acute emesis and delayed emesis. For patients experiencing breakthrough nausea and vomiting, the available evidence suggests the use of 10 mg oral olanzapine, daily for 3 days. Mild to moderate sedation in this patient population (especially elderly patients) is a potential problem with this agent.

Purpose Addition of rolapitant to standard antiemetic therapy improved protection against chemotherapy-induced nausea and vomiting (CINV) in phase 3 trials of patients receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Here, we assessed the impact of CINV on the daily lives of patients receiving HEC or MEC using the Functional Living Index-Emesis (FLIE). Methods In three double-blind phase 3 studies, patients receiving HEC or MEC were randomized 1:1 to receive oral rolapitant 180 mg or placebo prior to chemotherapy plus 5-hydroxytryptamine type 3 receptor antagonist and dexamethasone therapy. Patients completed the FLIE questionnaire on day 6 of cycle 1. Endpoints included FLIE total score, nausea and vomiting domain scores, and the proportion of patients with no impact on daily life (total score >108 [range 18–126]). We performed a prespecified analysis of the MEC/anthracycline-cyclophosphamide (AC) study and a post hoc analysis of two pooled cisplatin-based HEC studies. Results In the pooled HEC studies, rolapitant significantly improved the FLIE total score (114.5 vs 109.3, p

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.

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.

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 (cisplatinor =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 (doxorubicinor =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.

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.

The purpose of this study was to evaluate the efficacy and safety of four different doses of granisetron when administered as a single intravenous (i.v.) dose for prophylaxis of cisplatin-induced emesis in a multicenter, randomized, parallel-group, double-blind investigation. A total of 353 chemotherapy-naive patients were enrolled, stratified according to cisplatin dose (moderate dose: 50–80 mg/m2,n = 169; high dose: 81–120 mg/m2,n = 184) and randomized to one of four granisetron doses: 5, 10, 20, or 40 µ/kg. Control of emesis was evaluated by the percentages of patients attainingcomplete response (no vomiting or retching, and no rescue medication) andmajor response (≤2 episodes of vomiting or retching, and no rescue medication). Patients were assessed on an inpatient basis for 18–24 h. Safety analyses consisted of adverse events and laboratory parameter changes. Complete response rates over 24 h after chemotherapy were 23%, 48%, 48%, and 44% for granisetron doses of 5, 10, 20, and 40 µg/kg, respectively, in the combined patient population (P=0.011 for linear trend); 29%, 56%, 58%, and 41%, respectively, in the moderate-dose cisplatin stratum (P=0.278 for linear trend); and 18%, 41%, 40%, and 47%, respectively, in the high-dose cisplatin stratum (P = 0.011 for linear trend). Transient headache was the most frequently reported adverse event (19%). There was no evidence of association between increased dose and headache. A single 10-, 20- or 40-µg/kg dose of granisetron is comparably effective in controlling nausea and vomiting associated with moderateor high-dose cisplatin chemotherapy. Granisetron was safe and well tolerated at all doses.