The use of olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy

Purpose

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.

Methods

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.

Results

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.

Conclusions

Olanzapine was significantly better than metoclopramide in the control of breakthrough emesis and nausea in patients receiving highly emetogenic chemotherapy.     

Efficacy and safety of palonosetron for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV): a systematic review and meta-analysis of randomized controlled trials

Purpose

Palonosetron, a 5-hydroxytryptamine 3 receptor antagonist (5-HT₃RA) with a strong binding affinity and long half-life, has been used in numerous trials for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV). We systematically reviewed the efficacy and safety of palonosetron compared to other 5-HT₃RAs in CINV prophylaxis.

Methods

A literature search of Ovid MEDLINE, EMBASE, and CENTRAL was conducted to identify randomized controlled trials (RCTs) comparing palonosetron to other 5-HT₃RAs in CINV prophylaxis. Primary endpoints were the percentage of patients achieving a complete response (CR), complete control (CC), no emesis, no nausea, or taking no rescue medications. Secondary endpoints were the percentage of patients suffering from 5-HT₃RA-related adverse events.

Results

Sixteen RCTs were identified with 2,896 patients randomized to palonosetron and 3,187 patients randomized to other 5-HT₃RAs. Palonosetron was consistently statistically superior in CR, CC, no emesis, or no nausea and was sometimes superior in no rescue medication. Subgroup analyses demonstrated similarity in efficacy between highly and moderately emetogenic chemotherapy cohorts. In the acute phase, statistical superiority of palonosetron was found for trials that did not allow dexamethasone; conversely, RCTs that administered dexamethasone to all patients were nonsignificant. Palonosetron was statistically significantly safer in dizziness and mean QTc interval change and similar in constipation, headache, and diarrhea. Clinical superiority of palonosetron was reached in 3 of 19 analyzed efficacy and safety endpoints.

Conclusions

Palonosetron is safer and more efficacious than other 5-HT₃RAs. Future antiemetic guidelines should discuss the merits of including palonosetron as a first-line treatment.     

Perception of healthcare providers versus patient reported incidence of chemotherapy-induced nausea and vomiting after the addition of NK-1 receptor antagonists

Purpose  

Physicians and nurses often underestimate the incidence of chemotherapy-induced nausea and vomiting (CINV) after both highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC). This study assesses physicians’ and nurses’ perceptions of CINV in their own practices after the introduction of aprepitant.     

A phase II trial of olanzapine,dexamethasone, and palonosetron for the prevention of chemotherapy-induced nausea and vomiting: a Hoosier oncology group study

Objective 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. Materials and methods 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. Results 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. Discussion The complete response and control of nausea in subsequent cycles of chemotherapy were not significantly different from cycle one. Conclusion 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.     

Comparative clinical effectiveness of various 5-HT3 RA antiemetic regimens on chemotherapy-induced nausea and vomiting associated with hospital and emergency department visits in real world practice

Purpose  

The aim of this study was to compare the risk of chemotherapy-induced nausea and vomiting (CINV) events for various 5-HT₃ RAs in patients who received moderately (MEC) or highly emetogenic chemotherapy (HEC) by evaluating hospital or emergency department (ED) admissions.     

Incidence of chemotherapy-induced nausea and vomiting in Taiwan: physicians’ and nurses’ estimation vs. patients’ reported outcomes

Background The major objective of the study was to determine the incidence and prevalence of acute and delayed chemotherapy-induced nausea and vomiting (CINV) among patients receiving chemotherapy and assess the accuracy with which medical providers perceive the incidence of CINV in their practice.Methods Specialists, residents and nurses (medical providers) from two cancer centers in Taiwan estimated the incidence of acute and delayed CINV. Chemotherapy-naïve patients from the same centers then completed a 5-day nausea and vomiting diary following highly and moderately emetogenic chemotherapy (HEC and MEC) to determine the actual incidence of acute and delayed CINV. Daily nausea ratings were recorded on a 100-mm visual analogue scale (VAS). No nausea was defined as a nausea VAS score <5 mm. Vomiting episodes were also recorded. Nausea and vomiting were defined as acute and delayed based on whether they occurred during the first 24 h after chemotherapy, or during days 2–5 after chemotherapy, respectively.Results In the two oncology centers, 37 medical providers (13 specialists, 4 residents, 20 nurses) and 107 patients were enrolled. The mean patient age was 49.2 years with 76% female and 74% having breast cancer. Of the 107 patients, 39% received HEC and 61% received MEC, and 77% received a 5-HT3 receptor antagonist and 94% received dexamethasone. There were no significant differences between patients with acute CINV and delayed CINV in terms of demographics, chemotherapy treatment or antiemetic treatment. The proportion of patients without alcohol use was significantly higher among patients with delayed CINV than among those with non-delayed CINV. Good control of CINV during the acute period correlated with the control of delayed emesis. There were no significant differences between specialists, residents, and nurses estimations of the incidence rates of CINV. For HEC given to chemotherapy-naïve patients, the medical providers estimated acute CINV to be 44/41% and delayed CINV to be 61/53%, respectively. However, patient diaries revealed acute CINV to be 43/21% and delayed CINV to be 64/60%, respectively. For MEC given to chemotherapy-naïve patients, medical providers estimated acute CINV to be 39/36% and delayed CINV to be 44/39%, respectively. However, patient diaries revealed acute CINV to be 55/18% and delayed CINV to be 74/55%, respectively.Conclusions Medical providers significantly overestimated the incidence of acute vomiting by 20% and 18% in HEC and MEC patients, respectively. While they correctly estimated the rate of delayed vomiting in HEC patients, they underestimated it by 16% in MEC patients. With respect to nausea, medical providers correctly estimated rates of both acute and delayed nausea in HEC patients, but significantly underestimated rates of acute and delayed nausea by 16% and 30%, respectively, in MEC patients.     

Antiemetic prophylaxis and frequency of chemotherapy-induced nausea and vomiting in palliative first-line treatment of colorectal cancer patients: the Northern Bavarian IVOPAK I Project

Purpose

This study aims to evaluate adherence to guidelines of antiemetic prophylaxis and frequency of chemotherapy-induced nausea and vomiting (CINV) in the palliative first-line treatment of colorectal cancer (CRC) patients in Northern Bavaria.

Methods

We collected detailed information on chemotherapy and supportive drugs in 103 patients within a prospective observational study. The study was conducted to determine quality of care within an interdisciplinary context (first endpoint) and direct costs of palliative treatment for patients with CRC between 2006 and 2010 (second endpoint, Emmert et al. (Eur J Health Econ, 2012) [1]). In this paper, we evaluate adherence to Multinational Association of Supportive Care in Cancer (MASCC) 2006 recommendations for prophylaxis of CINV during the first administration of chemotherapy as well as incidence and grade of CINV within 120 h thereafter.

Results

Of the patients studied, 95 patients (92 %) received moderately emetogenic (oxaliplatin- and/or irinotecan-containing combined chemotherapy treatment) and eight (8 %) received low emetogenic chemotherapy (either 5-fluorouracil (5-FU) or capecitabine monotherapy). Antiemetic prophylaxis could be assessed in 101 out of 103 (98 %) of patients. MASCC-recommended antiemetic prophylaxis was prescribed in three patients (3 %). Nonadherence was mainly caused by omission of dexamethasone. Nausea and/or vomiting occurred in 18 patients (18 %) within a 120-h period. All documented episodes were grade 1 or 2 according to the Common Toxicity Criteria of the National Cancer Institute. None of these patients received the recommended prophylaxis for CINV. In only one patient, antiemetic prophylaxis was intensified during the next chemotherapy application.

Conclusions

In the Integrated Health Care in the Palliative Treatment of Colorectal Carcinoma (IVOPAK) I Project, adherence to the MASCC clinical recommendations was very poor. Extent of CINV in this patient population seems to be underestimated. There is an urgent need to improve clinicians' awareness of this patient-relevant side effect.     

Defining the efficacy of neurokinin-1 receptor antagonists in controlling chemotherapy-induced nausea and vomiting in different emetogenic settings—a meta-analysis

Purpose

This meta-analysis was performed to evaluate the efficacy of neurokinin-1 receptor antagonists (NK1RAs) for the prevention of chemotherapy-induced nausea and vomiting (CINV) across different categories of chemotherapeutic emetogenicity.

Methods

A systematic review of MEDLINE (via PubMed) and OVID databases, plus major oncology conferences, identified randomized, controlled trials evaluating NK1RAs in combination with a 5-HT₃ RA plus a glucocorticoid for management of CINV. Efficacy end points were no emesis, no nausea, and complete response (CR) rates. Data were analyzed using a random effects model.

Results

Twenty-three trials (N = 11,814) were identified. Based on absolute differences (AD) for no emesis (21 %), no nausea (8 %), CR (16 %), and odd ratios (OR) of 2.62, 1.43, and 2.16, respectively, NK1RA regimens provided better CINV protection versus control groups (all p < 0.00001) in patients receiving cisplatin-based highly emetogenic chemotherapy (HEC). In patients receiving anthracycline/cyclophosphamide (AC)-based HEC, respective ADs and ORs were 14, 4, and 11 % and 1.97 (p < 0.0001), 1.17 (p = 0.04), and 1.62 (p < 0.00001). In patients receiving moderately emetogenic chemotherapy (3 trials), no statistically significant benefit of NK1RAs was found; however, positive trends were detected for CR and no emesis. NK1RAs were effective for CINV prevention in a small number of studies using high-dose chemotherapy as conditioning prior to stem cell transplant and cisplatin-based multiple-day chemotherapy (MDC).

Conclusions

This meta-analysis demonstrated the efficacy of NK1RA in preventing vomiting in patients receiving HEC (including AC), with smaller effects on prevention of nausea. Efficacy is also seen with high-dose chemotherapy and cisplatin-based MDC.

     

Development and preliminary validation of a risk prediction model for chemotherapy-related nausea and vomiting

Background

A number of risk factors have been implicated in the development of chemotherapy-induced nausea/vomiting (CINV). Our aim was to develop a risk prediction model and identify patients at high risk for developing CINV before their chemotherapy treatment.

Patients and methods

A multisite, observational, prospective longitudinal design was used. Participants were 336 chemotherapy-naïve cancer patients providing 791 assessments. They completed measures to assess potential risk factors for CINV, including socio-demographic and clinical/treatment-related characteristics, symptom distress, expectations for CINV and state–trait anxiety. CINV was measured with the MASCC Antiemesis Tool. Participants were divided randomly to a training set (=286) and a test set (=50). Random-effects models were run to ascertain the contribution of risk factors in the development of CINV using the training sample. Specificity and sensitivity of the model were assessed in both sets of samples.

Results

Younger age, history of nausea/vomiting, trait anxiety and fatigue were linked with higher levels of CINV, and use of moderately and low emetogenic chemotherapy were linked with lower CINV. The model's specificity were 55.4 and 50.0 % and sensitivity were 80.3 and 79.0 % in the training and test sample, respectively. A dynamic web-based tool is freely available for use by clinicians.

Conclusion

This model of risk prediction for CINV can be an aid to clinical decision-making and assist clinicians to rationalise antiemetic use with their patients.     

The efficacy of triplet antiemetic therapy with 0.75 mg of palonosetron for chemotherapy-induced nausea and vomiting in lung cancer patients receiving highly emetogenic chemotherapy

Background

Chemotherapy-induced nausea and vomiting (CINV) are some of the most problematic symptoms for cancer patients. Triplet therapy consisting of a 5HT3 receptor antagonist, aprepitant, and dexamethasone is a guideline-recommended antiemetic prophylaxis for highly emetogenic chemotherapy (HEC). The efficacy and safety of triplet therapy using a 0.75-mg dose of palonosetron have not yet been investigated. We performed a prospective phase II study using triplet antiemetic therapy with 0.75 mg of palonosetron.

Methods

Chemotherapy-naïve lung cancer patients scheduled to receive HEC were enrolled. The eligible patients were pretreated with antiemetic therapy consisting of the intravenous administration of 0.75 mg of palonosetron, and 9.9 mg of dexamethasone and the oral administration of 125 mg of aprepitant on day 1, followed by the oral administration of 80 mg of aprepitant on days 2–3 and the oral administration of 8 mg of dexamethasone on days 2–4. The primary endpoint was the complete response rate (the CR rate; no vomiting and no rescue medication) during the overall phase (0–120 h).

Results

The efficacy analysis was performed in 63 patients. The CR rates during the overall, acute and delayed phases were 81.0, 96.8, and 81.0 %, respectively. The no nausea and no significant nausea rate during the overall phase were 54.0 and 66.7 %, respectively. The most common adverse event was grade 1 or 2 constipation.

Conclusions

Triplet antiemetic therapy using a 0.75-mg dose of palonosetron shows a promising antiemetic effect in preventing CINV in lung cancer patients receiving HEC.     

Aprepitant triple therapy for the prevention of chemotherapy-induced nausea and vomiting following high-dose cisplatin in Chinese patients: a randomized,double-blind,placebo-controlled phase III trial

Purpose

Aprepitant, an oral neurokinin-1 receptor antagonist, has demonstrated improved control of chemotherapy-induced nausea and vomiting (CINV) in previous studies. This is the first phase III study to evaluate the efficacy and tolerability of aprepitant in patients receiving highly emetogenic chemotherapy (HEC) in Asian countries.

Methods

This multicenter, double-blind, placebo-controlled trial assessed the prevention of CINV during the acute phase (AP), delayed phase (DP), and overall phase (OP). Patients receiving HEC were randomized to either an aprepitant group (day 1, aprepitant 125 mg; days 2–3, aprepitant 80 mg) or a standard therapy group (days 1–3, placebo). Both groups received intravenous granisetron and oral dexamethasone. The primary end point was complete response (CR; no emesis and no use of rescue therapy) during the OP.

Results

Of the 421 randomized patients, 411 (98 %) were assessable for efficacy; 69.6 % (142/204) and 57.0 % (118/207) of patients reported CR during the OP in the aprepitant and standard therapy groups, respectively (P?=?0.007). CR rates in the aprepitant group were higher during the DP (74.0 % vs. 59.4 %, P?=?0.001) but were similar during the AP (79.4 % vs. 79.3 %, P?=?0.942). Toxicity and adverse events were comparable in both groups.

Conclusions

The addition of aprepitant to standard antiemetic treatment regimens for Chinese patients undergoing HEC provided superior CINV prevention and was well tolerated.     

Resource utilization and costs associated with chemotherapy-induced nausea and vomiting (CINV) following highly or moderately emetogenic chemotherapy administered in the US outpatient hospital setting

Purpose  

Chemotherapy-induced nausea and vomiting (CINV), common adverse events of chemotherapy, may be associated with considerable healthcare resource utilization. This study was conducted to describe CINV-associated healthcare visits and costs following a first cycle of highly or moderately emetogenic chemotherapy (HEC or MEC).     

Palonosetron in combination with 1-day versus 3-day dexamethasone for prevention of nausea and vomiting following moderately emetogenic chemotherapy: a randomized, multicenter, phase III trial

Purpose

A phase III trial assessed the efficacy of palonosetron plus dexamethasone given once in preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV) following a broad range of moderately emetogenic chemotherapy (MEC) regimens.

Methods

This multicentre, randomized, open-label, non-inferiority trial evaluated two different treatment groups. One group received palonosetron (0.25?mg intravenously) and dexamethasone (8?mg intravenously) before chemotherapy, while the other was administered the same regimen on day?1 followed by dexamethasone 8?mg orally on days?2 and 3. The primary endpoint was complete response (CR; defined as no emetic episodes and no rescue medication) during the overall phase (days?1?C5 after chemotherapy initiation). The non-inferiority margin was predefined as a 15% difference between groups in the primary endpoint.

Results

Of 332 chemotherapy-na?ve patients included in the intention-to-treat analysis, 65.1% were female, and 35.2% received anthracycline plus cyclophosphamide (AC)-based regimens. Overall CR rates were 67.5% for those administered dexamethasone only on day?1 (n?=?166), and 71.1% for those also administered dexamethasone on days?2 and 3 (n?=?166; difference ?3.6% (95% confidence interval, ?13.5 to 6.3)). CR rates were not significantly different between groups during the acute (0?C24?h post-chemotherapy; 88.6% versus 84.3%; P?=?0.262) and delayed phases (days?2?C5; 68.7% versus 77.7%; P?=?0.116).

Conclusions

Palonosetron plus single-dose dexamethasone administered before common MEC regimens provide protection against acute and delayed CINV which is non-inferior to that of palonosetron plus dexamethasone for 3?days. However, the major benefit of the single-day regimen occurs in patients receiving non-AC MEC regimens.     

Aprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with a broad range of moderately emetogenic chemotherapies and tumor types: a randomized, double-blind study

Purpose  

Aprepitant was shown previously to be effective for prevention of chemotherapy-induced nausea and vomiting (CINV) with moderately emetogenic chemotherapy (MEC) in breast cancer patients receiving an anthracycline and cyclophosphamide (AC)-based regimen. This study assessed aprepitant in patients receiving a broad range of MEC regimens with a variety of tumor types.     

Adherence to antiemetic guidelines in patients with malignant glioma: a quality improvement project to translate evidence into practice

Purpose

A quality improvement project was implemented to improve adherence to evidence-based antiemetic guidelines for malignant glioma patients treated with moderately emetic chemotherapy (MEC). Poorly controlled chemotherapy-induced nausea and vomiting (CINV) reduce cancer treatment efficacy and significantly impair cancer patients’ quality of life (QOL). A review of Duke University Preston Robert Tisch Brain Tumor Center (PRTBTC)’s usual practice demonstrates a high incidence (45 %) of CINV, despite premedication with short-acting 5-HT₃-serotonin-receptor antagonists (5-HT₃-RAs). National Comprehensive Cancer Network (NCCN)’s evidence-based guidelines recommend the combination of the long-acting 5-HT₃-RA palonosetron (PAL) and dexamethasone (DEX) for the prevention of acute and delayed CINV with MEC. Low adherence (58 %) to antiemetic guidelines may have explained our high CINV incidence.

Methods

One-sample binomial test, quasi-experimental design, evaluated a combination intervention that included a provider education session; implementation of risk-assessment tool with computerized, standardized antiemetic guideline order sets; and a monthly audit-feedback strategy. Post-implementation adherence to evidence-based antiemetic order sets and patient outcomes were measured and compared to baseline and historical data. Primary outcome was the guideline order set adherence rate. Secondary outcomes included nausea/vomiting rates and QOL.

Results

Adherence to ordering MEC guideline antiemetics increased significantly, from 58 % to a sustained 90 %, with associated improvement in nausea/vomiting. In acute and delayed phases, 75 and 84 % of patients, respectively, did not experience CINV. There was no significant change in QOL.

Conclusion

Combination intervention and audit-feedback strategy to translate evidence into oncology practice improved and sustained adherence to antiemetic guidelines. Adherence corresponded with effective nausea/vomiting control and preserved QOL in patients with malignant gliomas.     

Single-dose palonosetron for prevention of chemotherapy-induced nausea and vomiting in patients with aggressive non-Hodgkin's lymphoma receiving moderately emetogenic chemotherapy containing steroids: results of a phase II study from the Gruppo Italiano per lo Studio dei Linfomi (GISL)

Purpose

The control of nausea and vomiting induced by chemotherapy is paramount for overall treatment success in cancer patients. Antiemetic therapy during chemotherapy in lymphoma patients generally consists of anti-serotoninergic drugs and dexamethasone. The aim of this trial was to evaluate the efficacy of a single dose of palonosetron, a second-generation serotonin type 3 (5-HT₃) receptor antagonist, in patients with aggressive non-Hodgkin's lymphoma receiving moderately emetogenic chemotherapy (MEC) containing steroids.

Methods

Patients received a single intravenous bolus of palonosetron (0.25?mg) before administration of chemotherapy. Complete response (CR) defined as no vomiting and no rescue therapy during overall phase (0?C120?h) was the primary endpoint. Complete control (CC) defined as CR and only mild nausea was a secondary endpoint.

Results

Eighty-six evaluable patients entered in the study. A CR was observed in 74 patients (86.0%) during the overall phase; the CR during the acute (0?C24?h) and delayed (24?C120?h) phases was 90.7% and 88.4%, respectively. CC was 89.5% during the acute and 84.9% during the delayed phase; the overall CC was 82.6%.

Conclusions

This was the first trial, which demonstrated the efficacy of a single dose of palonosetron in control CINV in patients with aggressive non-Hodgkin??s lymphoma receiving MEC regimen containing steroids.     

Casopitant improves the quality of life in patients receiving highly emetogenic chemotherapy

Purpose  

The control of chemotherapy-induced nausea and vomiting (CINV) is critical in preventing poor health outcomes and increasing patient quality of life. The objective of this study was to evaluate the impact of the addition of casopitant to dual-combination therapy of dexamethasone and ondansetron on quality of life in patients receiving highly emetogenic chemotherapy (HEC).     

Efficacy,tolerability, and safety of cannabinoids for chemotherapy-induced nausea and vomiting—a systematic review of systematic reviews

Background

There is growing public and legislative body support for the medical use of cannabis products, for example, for chemotherapy-induced nausea and vomiting (CINV), in Germany.

Methods

A comprehensive literature search until November 2015 was conducted in MEDLINE, DARE and Cochrane libraries for systematic reviews of randomized controlled trials (RCTs) comparing herbal or pharmaceutical cannabinoids (CB) versus placebo or conventional antiemetics for CINV. Outcomes were reduction of CINV for efficacy, drop-out rates due to adverse events for tolerability, and serious adverse events for safety. The methodology quality of the systematic reviews was evaluated by the tool assessment of multiple systematic reviews (AMSTAR).

Results

Six systematic reviews of RCTs included the pharmaceutical CBs dronabinol, levonantradol, and nabilone or whole plant extract (e.g., nabiximol) compared with placebo or conventional antiemetics. There was moderate quality evidence on the efficacy of CBs compared to placebo and conventional antiemetics for CINV. There was moderate quality evidence that pharmaceutical CBs were less tolerated and less safe than placebo and conventional antiemetics in CINV. One RCT examining whole plant extract was included into the systematic reviews. No RCT was found comparing CBs with neurokinine?1 receptor antagonists.

Conclusions

With safe and effective antiemetics available, CBs cannot be recommended as first- or second-line therapy for CINV. Some guidelines recommend pharmaceutical CBs as third-line treatment in the management of breakthrough nausea and vomiting. Due to the lack of RCT data and safety concerns, herbal cannabis cannot be recommended for CINV.