Control Of Chemotherapy-induced Nausea And Vomiting Research Articles

Neiguan (PC6) acupoint stimulation for preventing chemotherapy-induced nausea and vomiting: a cost-effective supplement in guideline-inconsistent chemotherapy-induced nausea and vomiting prophylaxis subgroup.

To assess the efficacy and safety of Neiguan (PC6) acupoint acustimulation in preventing chemotherapy-induced nausea and vomiting (CINV), especially for patients with guideline-inconsistent CINV prophylaxis (GICP) due to personal reasons METHODS: From January 2021 to December 2021, 373 patients suffered from solid malignancy were recruited according to the inclusion criteria. Complete response (no emesis and no rescue medication use) rate during the overall phase (0-120 h of each chemo-cycle) was the primary assessment of CINV control. The Functional Living Index-Emesis (FLIE) questionnaire was investigated among these patients as a secondary 'quality of life' objective to assess the impact of CINV on patients' daily life by recording score of nausea and vomiting. With acustimulation of Neiguan (PC6) acupuncture point through a portable, noninvasive and user-friendly device, in terms of complete response rate and scores in nausea/vomiting by FLIE questionnaire, patients achieve a better outcome in highly emetogenic chemotherapy (HEC) induced CINV, especially GICP subgroup. Meanwhile, analysis also demonstrated this tendency existed in other patients with HEC/GCCP (guideline consistent CINV prophylaxis) and moderate emetogenic chemotherapy, although the difference was not significant. Considering advantages of Neiguan (PC6) acustimulation such as noninvasive, covered by medical insurance and few side effects, we believe it would be an ideal auxiliary tool in CINV control, especially in patients who receive highly emetogenic chemo-protocol and are reluctant to GCCP for economic reasons.

Outcome of antiemetic prophylaxis among pediatric cancer patients receiving moderate to highly emetogenic chemotherapy at pediatric hemato-oncology ward of Tikur Anbessa specialized hospital: A prospective observational study.

Chemotherapy-induced nausea and vomiting (CINV) is a major issue for chemotherapy pediatric patients, especially in developing countries due to limited access to essential antiemetics. This study aimed to assess antiemetic prophylaxis outcomes in pediatric cancer patients at Tikur Anbessa Specialized Hospital in Addis Ababa, Ethiopia. A longitudinal prospective observational study design was conducted among 201 pediatric cancer patients followed up to 120 h post-chemotherapy. The majority of patients (75.1%) received combination prophylactic antiemetics in the acute phase. Complete response (CR) was the highest in the acute phase (71.1%). Emesis episodes occurred most frequently on the first day of treatment (28.4%) and gradually decreased over time. History of motion sickness, platinum-based chemotherapy, and prior chemotherapy-induced vomiting (CIV) were associated with emesis during the acute phase whereas multiple-day chemotherapy, prior CIV, receipt of antiemetics, and a history of motion sickness in the delayed phase. However, the odds of CIV were reduced with steroid presence in the chemotherapy regimen. A considerable number of participants could not achieve a CR. It is important for clinicians to be cognizant of risk factors that influence the outcome of antiemetic prophylaxis to achieve better control of CINV among pediatric cancer patients.

Abstract PO1-11-12: Factors associated with treatment failure for chemotherapy-induced nausea and vomiting (CINV) among breast cancer patients receiving adjuvant chemotherapy

Abstract Background Cancer patients often consider CINV as one of the most disturbing side effects of cytotoxic chemotherapy. Adriamycin and cyclophosphamide (AC), considered by many to be part of the standard adjuvant regimen for breast cancer patients, is highly emetogenic. Despite adopting optimal antiemetic prophylaxis, the control of CINV remains modest for some patients. Among Chinese breast cancer patients receiving adjuvant AC chemotherapy, the present analysis aims to determine the association of the number of risk factors for CINV with (i) likelihood of antiemetic treatment failure; (ii) time to first vomiting in 1st AC cycle. Methods: We retrieved data from three previously reported prospective antiemetic studies on patients who received AC, in whom different antiemetic regimens were administered. Treatment failure was defined as (i) not achieving CR (CR= no vomiting and no use of rescue medication over 120 hours after start of AC), or (ii) experiencing nausea (nausea VAS >/= 5mm during the 120 hours). Multivariate logistic regression models were applied to identify potential factors associated with the development of CINV. The Cochran–Armitage trend test was utilized to assess possible trends in the relationship between treatment failure and number of identified risk factors. The time-to-treatment failure curves, as classified by the number of identified factors in each subgroup, were evaluated using the Kaplan–Meier method. Results: Based on multivariate analysis of 303 breast cancer patients, not achieving CR was more likely among non-obese patients, not receiving guideline recommended prophylactic antiemetic regimens, history of motion sickness and history of vomiting in pregnancy. Experience of nausea was more likely in non-obese patients, not receiving guideline recommended prophylactic antiemetic regimens, and history of motion sickness. Treatment failure in terms of ‘no CR’ was associated with increased number of risk factors that an individual patient displayed; the figures increased from 18.8% for those with 0 risk factor to 94.1% for those with 4 risk factors (p < 0.0001). Treatment failure in terms of nausea was associated also with increased number of risk factors; the figures increased from 25.9% for those with 0 risk factor to 83.3% for patients with 3 risk factors (p < 0.0001). Time to first vomiting was significantly related to number of identified factors (p < 0.0001). Among patients who had 0, 1, 2 and 3 risk factors, the 24-hour rate of ‘no vomiting’ were 81.3%, 80.3%, 66.7%, 53.7% and 17.7%, respectively; similar trends were observed for analyses on 48-hour and 72-hour rates. Conclusions: The present study confirmed that reported risk factors for CINV in the literature were important in Chinese breast cancer patients receiving AC chemotherapy. Furthermore, patients who had more risk factors had increased likelihood of treatment failure and shorter time to first vomiting. Funding: Madam Diana Hon Fun Kong Donation for Cancer Research Citation Format: Winnie Yeo, Nicole Ngai, Horatio Yeo, Dong Lai, Elizabeth Pang, Carol Kwok, Thomas Lau, Frankie Mo. Factors associated with treatment failure for chemotherapy-induced nausea and vomiting (CINV) among breast cancer patients receiving adjuvant chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-11-12.

A nurse-led multidomain intervention to improve the management of chemotherapy-induced nausea and vomiting in patients with head and neck cancers: A randomized controlled trial

PurposeThis study aimed to investigate the effect of a nurse-led multidomain intervention on chemotherapy induced nausea and vomiting (CINV) in patients with head and neck squamous cell carcinomas (HNSCC). MethodsNinety-two HNSCC patients who received cisplatin-based chemotherapy were divided into intervention group (n = 45) and control group (n = 47). The control group received usual care of CINV, which consisted of administration of antiemetics according to physicians' preference, education about CINV control and dietary recommendations provided by primary nurses. The intervention group received nurse-led, evidence-based multidomain management, including nurse-led CINV risk factors assessment, education on prevention and control of CINV, antiemetics following guidelines, dietary strategies, and relaxation therapy. The number of patients who experienced CINV was collected. The severity of CINV was graded according to the Common Terminology Criteria for Adverse Events v3.0. The influence of CINV on patient's quality of life was assessed by the Functional Living Index-Emesis (FLIE). ResultsThe incidence and the severity of nausea and vomiting in the intervention group were significantly lower than those in the control group within 5 days after chemotherapy, and the scores of the dimension of nausea and vomiting in the intervention group were significantly higher than those in the control group [63.00 (50.00–63.00) vs 40.00(28.00–63.00), 63.00(63.00–63.00) vs 63.00 (43.00–63.00)], the differences were statistically significant (P < 0.05). ConclusionsNurse-led multidomain intervention can reduce the incidence and the severity of CINV in patients with HNSCC who were treated with cisplatin-based chemotherapy, and thus reduced the influence of CINV on patients' quality of life. The clinical trial registration numberNCT05792228.

Risk Factors Associated with Chemotherapy-Induced Nausea and Vomiting Among Women with Breast Cancer Receiving Highly Emetogenic Chemotherapy: Individual Patient-Based Analysis of Three Prospective Antiemetic Trials.

Although risk factors related to chemotherapy-induced nausea and vomiting (CINV) have been identified in previous studies, only a few studies have evaluated the risk factors associated with contemporary antiemetic prophylaxis, including olanzapine/aprepitant- or NEPA-containing regimens. This study aimed to identify the risk factors associated with CINV development in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide chemotherapy. Data from 304 patients enrolled in 3 previously reported prospective antiemetic studies were included. Multivariate logistic regression models were used to predict risk factors associated with CINV occurrence. Additionally, the likelihood of treatment failure in relation to the number of risk factors in individual patients was evaluated. Multivariate analysis of the entire study group revealed that obesity status (defined as body mass index/= 25.0 kg/m2) and the use of olanzapine/aprepitant- or NEPA-containing anti-emetic regimens were associated with a high likelihood, while a history of motion sickness was associated with a lower likelihood, complete response (CR), and "no nausea" in the overall phase. A history of vomiting during pregnancy was also associated with a lower likelihood of an overall CR. Patients with an increasing number of risk factors had a higher likelihood of treatment failure and shorter time to first vomiting. Those who did not achieve CR and "no nausea" in the first cycle were less likely to achieve these parameters in the subsequent cycle of chemotherapy. The present study confirmed previously reported risk factors for CINV in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide. Further optimization of CINV control is required for patients with identifiable risk factors; olanzapine/aprepitant- or NEPA- containing prophylaxis are the preferred contemporary anti-emetics regimens for Chinese breast cancer patients undergoing doxorubicin and cyclophosphamide chemotherapy.

Pediatric oncology provider perspectives and patient/family perceptions of chemotherapy-induced nausea and vomiting management: Experiences at an academic medical center.

Chemotherapy-induced nausea and vomiting (CINV) is common in children undergoing cancer treatment, and significantly impacts quality of life. Clinical practice guidelines (CPGs) have been developed to guide CINV management, though many patients do not receive guideline-concordant care. Few studies have examined provider perspectives on CINV management or preferred improvement approaches, or pediatric patient perception of CINV control. A cross-sectional study of pediatric oncology providers was conducted at a large freestanding children's hospital. Providers completed an anonymous online survey about CINV control in patients admitted for scheduled chemotherapy, and their knowledge and utilization of CINV CPGs. A survey of English and Spanish-speaking pediatric oncology patients admitted for scheduled chemotherapy was conducted to assess CINV management, with key demographics used to understand association with perceptions and adherence to antiemetic guidelines. For providers, 75% of respondents felt CINV management could be moderately or extremely improved, significantly more so by chemotherapy prescribers and pediatric medical residents than nurses. Over half of respondents did not have awareness of CINV CPGs, particularly pediatric medical residents. For patients, nausea was reported to be extremely well controlled in 44% of cases, and vomiting extremely well controlled in 50% of cases. There were no significant differences in patient-reported CINV across demographics, when considering emetogenicity of chemotherapy received, or concordance to guidelines. Implementing education in this area may help to improve provider comfort, and ultimately, the patient experience. Future studies will expand upon this novel patient perception, and develop and evaluate CINV management interventions.

Prevention of CINV in Patients with Multiple Myeloma or Lymphoma Undergoing Hematopoietic Stem Cell Transplantation: NEPA Versus Ondansetron. a Monocentric Real-Life Experience

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) are adverse events that compromise quality of life and treatment compliance in patients undergoing autologous hematopoietic stem cell transplantation (ASCT). Polychemotherapy regimens, used as conditioning regimens for ASCT in lymphomas, and high-dose melphalan (≥140 mg/mq), used in multiple myeloma (MM), have high emetogenic risk. Control of CINV is difficult and there is no uniformity for its prophylaxis. Antiemetic guidelines recommend, for prophylaxis, co-administration of a triplet regimen of a serotonine (5-HT3) receptor antagonist (RA), as Ondansetron, a neurokinin-1 RA, and dexamethasone. Netupitant-Palonosetron (NEPA), an oral formulation derived from the combination of Netupitant (NK1-RA) and Palonsetron, has been approved as prophylaxis of CINV but its experience in the stem cell transplant setting is still limited. AIMS: The primary aim of this study was to compare the efficacy of Ondansetron versus NEPA in terms of reduction of CINV in patients affected by lymphoma or MM who undergone ASCT. The secondary aims included comparing the duration of CINV, based on the use of Ondansetron or NEPA, and their safety profile in terms of reduction of extrahaematological toxicity (as mucositis or diarrhea). METHODS: In this retrospective monocentric study, we enrolled 76 patients (48 with MM and 28 with lymphoma), who underwent ASCT between March 2021 and March 2022. All patients with MM received high dose of melphalan, those with lymphoma received FEAM. Regarding antiemetics patients were divided according to whether they received NEPA or Ondansetron .Patients' characteristics are in Table 1. RESULTS: Among all, fifty patients (65%) reported CINV of any grade. In particular, the group experiencing CINV included about half of patients treated with NEPA (56%) and almost all those treated with Ondansetron (91%). Among the 26 patients who didn't report CINV (35%), the majority received NEPA (92%) (P = 0.0032)(Fig. 1a). Focusing on patients with MM, 33 experienced CINV (68%), and they were 59% of MM patients treated with NEPA and 93% of those treated with Ondansetron. Fifteen patients did not experience CINV (32%) and almost all of them (93%) had been treated with NEPA (P = 0.037)(Fig. 1b). Sixty-one percent of the 28 patients with lymphoma reported CINV (P= 0.1914) (Fig. 1c). Mean duration of CINV was significantly shorter for patients treated with NEPA than for those treated with Ondansetron (4.8 days vs 9.2 days) (P= 0.002) (Fig. 1d). Regarding extraematological toxicity of chemotherapy, as mucositis and diarrhea, we didn't find any significant difference between the two groups of patients. Regarding the outcome to NEPA, complete response rate (no emesis, no rescue medication) was 37% during overall phases of CINV, 28% of patients had complete control (complete response with no more than mild nausea) and 31% had uncontrolled nausea. Conversely, in the Ondansetron group, only 5% of patients had complete response and 95% had uncontrolled nausea (Fig. 1e). All patients with uncontrolled nausea required a rescue therapy. According to CTCAE, 69% of patients receiving NEPA had grade 1 nausea and 6% had none, while all patients receiving Ondansetron had CINV and 85% of them had grade 2 nausea. CONCLUSIONS: In our experience, NEPA has shown superiority in the prevention of CINV, in highly emetogenic regimens in both patients with myeloma or lymphoma, with advantages on the severity and the duration of CINV. Given the high burden of CINV in the whole population analyzed in the study, regardless of the antiemetic used, it would be useful to identify patients at greatest risk and standardize CINV prophylaxis and treatment protocols depending on the different chemotherapy regimens and their emetogenic risk.

Assessment of the change of antiemetic prophylaxis from double to triple combination in patients with high dose carboplatin chemotherapy.

Chemotherapy-induced nausea and vomiting (CINV) is one of the adverse events that most affects oncologic patients' quality of life. Carboplatin AUC ≥ 4 belongs to agents with high emetic risk (moderate risk in ASCO guidelines). We aimed to compare the effectiveness of netupitant/palonosetron and dexamethasone triple combination (TC) therapy versus ondansetron and dexamethasone double combination (DC) therapy as antiemetic prophylaxis in patients with carboplatin AUC ≥ 4. As a secondary endpoint, in TC group we evaluated the effectiveness of changing NEPA administration timing from 1 h to 15 min before chemotherapy. Open-label prospective study conducted in a tertiary-care hospital in patients receiving carboplatin AUC ≥ 4. CINV was evaluated using MASCC antiemetic tool, in acute (<24 h) and delayed phase (24-120 h). Results were analyzed using χ2 test. Two-hundred four completed questionnaires (CQ) were analyzed (76 in DC and 128 in TC). The proportion of patients who remained emesis-free was superior for TC-treated group compared to DC, either in acute (99.2% vs 92.1%, p = 0.0115) and delayed phase (97.6% vs 90.7%, p = 0.043). Likewise, a higher proportion of TC-treated patients compared to DC remained nausea-free for the first 24 h after treatment (90.6% vs 71%, p = 0.0004) and between 24 and 120 h (82.3% vs 62.7%, p = 0.0025). The change of NEPA administration time showed similar effectiveness in terms of CINV control (81.6% vs 74.5%, p = 0.70). TC showed superiority in early and delayed CINV control in carboplatin AUC ≥ 4 regimens, with no significant differences among cancer types. Change in NEPA administration timing has beneficial implications; it allows NEPA to be administered at hospitals before chemotherapy session.

Fosaprepitant Weekly vs Every 3 Weeks for the Prevention of Concurrent Chemoradiotherapy–Induced Nausea and Vomiting

Unlike substantial evidence in the prevention of chemotherapy-induced nausea and vomiting (CINV), research in the prevention of nausea and vomiting caused by concurrent chemoradiotherapy (CCRT) is currently lacking. To compare the efficacy and safety of fosaprepitant weekly vs every 3 weeks for the prevention of nausea and emesis caused by CCRT among patients with nasopharyngeal carcinoma. This pilot randomized clinical trial was conducted at a single cancer center from November 24, 2020, to July 26, 2021, among patients with nasopharyngeal carcinoma who had achieved CINV control after 2 to 3 cycles of induction chemotherapy. Efficacy analyses were performed in the intention-to-treat population. Data were analyzed on November 4, 2022. Eligible patients were randomly assigned (1:1) to receive fosaprepitant either weekly or every 3 weeks. The primary end point was the proportion of patients with sustained complete response (defined as no emesis and no rescue therapy) during CCRT. Secondary end points were sustained no emesis, no nausea, no significant nausea, mean time to first emetic episode, quality of life, and 1-year progression-free survival (PFS). A total of 100 patients (mean [SD] age, 46.6 [10.9] years; 83 [83.0%] male) who had achieved CINV control after induction chemotherapy were randomly assigned to receive fosaprepitant weekly (50 patients) or every 3 weeks (50 patients). There was no significantly significant difference in cumulative risk of emesis or rescue therapy in the group that received weekly fosaprepitant compared with those who received fosaprepitant every 3 weeks (subhazard ratio, 0.66 [95% CI, 0.43-1.02]; P = .06). The proportion of patients with sustained no emesis (38% vs 14%; P = .003) or no significant nausea (92% vs 72%; P = .002) was significantly higher in the group that received fosaprepitant weekly vs those who received fosaprepitant every 3 weeks. Treatments were well tolerated. Patients in the weekly group had improved scores for multiple quality-of-life measures. There was no significant difference in survival outcomes between groups (91.8% vs 93.7%; P = .99). In the mean brainstem dose subgroups, a possible treatment interaction effect was observed in sustained complete response (mean brainstem dose ≥36 Gy: hazard ratio [HR], 0.32 [95% CI, 0.15-0.69]; mean brainstem dose <36 Gy: HR, 0.95 [95% CI, 0.55-1.63]) and sustained no emesis (mean brainstem dose ≥36 Gy: HR, 0.21 [95% CI, 0.08-0.53]; mean brainstem dose <36 Gy: HR, 0.73 [95% CI, 0.41-1.28]). In this pilot randomized clinical trial, there was no statistically significant difference in the complete response primary end point, but patients receiving weekly fosaprepitant were less likely to experience emesis compared with those who received fosaprepitant every 3 weeks, especially in the subgroup with a mean brainstem dose of 36 Gy or more. Weekly fosaprepitant was well tolerated and improved quality of life of patients without compromising survival. ClinicalTrials.gov Identifier: NCT04636632.

Possibilities of prevention of nausea during cytostatic therapy: literature review and clinical cases

Chemotherapy-induced nausea and vomiting (CINV) is a side effect of cancer treatment, affecting up to 40% of patients. Nausea and vomiting are the most dangerous and also the most common side effects among patients undergoing chemotherapy. CINV remains one of the most worrisome syndromes associated with cancer therapy and can lead to dehydration, electrolyte imbalances, malnutrition, and metabolic disorders. Risk factors for developing CINV include the patient’s gender and age, a history of CINV, and the emetogenicity and timing of chemotherapy. Options for preventing CINV are 5-HT3 receptor antagonists (i.e., ondansetron, granisetron, palonosetron) in combination with corticosteroids (i.e., dexamethasone) or additionally in combination with NK1 receptor antagonists (i.e., aprepitant, fosaprepitant, netupitant, rolapitant). Palonosetron is a selective 5-hydroxytryptamine 3 (5-HT3) receptor antagonist. The effectiveness of palonosetron for delayed nausea and vomiting is also supported by the results of three randomized trials that demonstrated no side effects of the simplified regimen with palonosetron and single dose dexamethasone for the control of CINV associated with moderately emetogenic chemotherapy or AC regimen. A clinical observation of the treatment of a young patient with breast cancer is given. After the first course of chemotherapy, the patient developed a rather serious complication in the form of vomiting, which required hospitalization for infusion therapy. The above clinical observation demonstrates the effectiveness of palonosetron in neo-adjuvant chemotherapy in a young patient, which made it possible to complete the entire course of treatment. After completion of neo-adjuvant chemotherapy, a radical operation was performed and a complete morphological response was noted.

Acupuncture for the prevention of chemotherapy-induced nausea and vomiting in cancer patients: A systematic review and meta-analysis.

To assess the effectiveness and safety of acupuncture for the prevention of chemotherapy-induced nausea and vomiting (CINV), with a specific intention on exploring sources of between-study variation in treatment effects. MEDLINE, EMBASE, Cochrane CENTRAL, CINAHL, Chinese Biomedical Literature Database, VIP Chinese Science and Technology Periodicals Database, China National Knowledge Infrastructure, and Wanfang were searched to identify randomized controlled trials (RCTs) that compared acupuncture to sham acupuncture or usual care (UC). The main outcome is complete control (no vomiting episodes and/or no more than mild nausea) of CINV. GRADE approach was used to rate the certainty of evidence. Thirty-eight RCTs with a total of 2503 patients were evaluated. Acupuncture in addition to UC may increase the complete control of acute vomiting (RR, 1.13; 95% CI, 1.02 to 1.25; 10 studies) and delayed vomiting (RR, 1.47; 95% CI, 1.07 to 2.00; 10 studies) when compared with UC only. No effects were found for all other review outcomes. The certainty of evidence was generally low or very low. None of the predefined moderators changed the overall findings, but in an exploratory moderator analysis we found that an adequate reporting of planned rescue antiemetics might decrease the effect size of complete control of acute vomiting (p = 0.035). Acupuncture in addition to usual care may increase the complete control of chemotherapy-induced acute vomiting and delayed vomiting but the certainty of evidence was very low. Well-designed RCTs with larger sample sizes, standardized treatment regimens, and core outcome measures are needed.

Treatment of breakthrough and prevention of refractory chemotherapy-induced nausea and vomiting in pediatric cancer patients: Clinical practice guideline update.

This clinical practice guideline update provides recommendations for treating breakthrough chemotherapy-induced nausea and vomiting (CINV) and preventing refractory CINV in pediatric patients. Two systematic reviews of randomized controlled trials in adult and pediatric patients informed the recommendations. In patients with breakthrough CINV, escalation of antiemetic agents to those recommended for chemotherapy of the next higher level of emetogenic risk is strongly recommended. A similar recommendation to escalate therapy is made to prevent refractory CINV in patients who did not experience complete breakthrough CINV control and are receiving minimally or low emetogenic chemotherapy. A strong recommendation to use antiemetic agents that controlled breakthrough CINV for the prevention of refractory CINV is also made.

The clinical research study for fosaprepitant to prevent chemotherapy-induced nausea and vomiting: A review.

In recent years, chemotherapy-induced nausea and vomiting (CINV) has become the most common adverse effect of chemotherapy in oncology patients. The CINV may reduce the quality of life in mild cases, or even make the patients resist or delay further treatment. Fosaprepitant is a newly marketed neurokinin-1 receptor antagonist (NK-1RA), which can be combined with 5-hydroxytryptamine 3 receptor antagonists (5-HT3RAs) and dexamethasone to prevent chemotherapy-induced vomiting. The dimeglumine salt form of fosaprepitant can be utilized as an intravenous injectable drug, which surpasses aprepitant's oral admistration limits. Fosaprepitant is effective and safe in the control of CINV in cancer patients receiving highly emetogenic chemotherapy (HEC), and may be an alternative option for antiemetic therapy. In general, fosaprepitant is worthy of clinical promotion and has a large market potential. This article reviews the clinical studies on fosaprepitant conducted in recent years, with the aim of providing a basis for the rational clinical selection of antiemetic drugs.

Abstract P3-03-03: Risk factors associated with chemotherapy-induced nausea and vomiting among breast cancer patients receiving highly emetogenic chemotherapy

Abstract Purpose: Although risk factors related to chemotherapy-induced nausea and vomiting (CINV) have been identified by prior studies, there are only few studies evaluating risk factors associated with the contemporary antiemetic prophylaxis, including that of olanzapine/aprepitant- or NEPA- containing regimens. The present study aimed to identify the risk factors related to CINV development in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide chemotherapy. Methods: Data from 304 patients who were enrolled to 3 previously reported prospective antiemetic studies were included. Multivariate logistic regression models were used to predict risk factors associated with the occurrence of CINV. Additionally, likelihood of treatment failure in relation to number of risk factors of individual patient was evaluated. Results: Multivariate analysis of the entire study group revealed that obese status (defined as body mass index &amp;gt;/= 25.0 kg/m2) and the use of olanzapine/aprepitant- or NEPA- containing antiemetic regimens were associated with high likelihood, while history of motion sickness was associated with lower likelihood, of complete response (CR) and ‘no nausea’ in the overall phase. History of vomiting in pregnancy was also associated with lower likelihood of overall CR. Patients with increasing number of risk factors had higher likelihood of treatment failure as well as shorter time to first vomiting. Those who did not achieve CR and ‘no nausea’ in the first cycle were less likely to achieve these parameters in the subsequent cycle of chemotherapy. Conclusions: This present study confirmed the previously reported risk factors to be important for CINV in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide. Further optimization of CINV control is required for patients with identifiable risk factors; olanzapine/aprepitant- or NEPA- containing prophylaxes are the preferred contemporary antiemetics regimens for Chinese breast cancer patients undergoing doxorubicin and cyclophosphamide chemotherapy. Citation Format: Winnie Yeo, Nicole Ngai, Christopher Yip, Victoria Yeo, Jonathan Ko, Claudia Yip, Frankie Mo. Risk factors associated with chemotherapy-induced nausea and vomiting among breast cancer patients receiving highly emetogenic chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-03.

Effect of Mirtazapine for the Prevention of Nausea and Vomiting in Patients With Thoracic Cancer Receiving Platinum-based Chemotherapy.

Mirtazapine, which exerts an antagonistic effect on 5-hydroxytryptamine type 5-HT2A, 5-HT2C, 5-HT3 and H1 receptors, is considered useful for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV). This study investigated the efficacy and safety of mirtazapine for the prevention of CINV in patients with thoracic cancer receiving platinum-based chemotherapy. A retrospective cohort study was conducted in patients with thoracic cancer receiving platinum-based chemotherapy with 15 mg mirtazapine once daily as a prophylactic antiemetic drug between January 2014 and December 2021. The effects of mirtazapine added to the standard antiemetic regimen for the prevention of CINV were evaluated in patients who had poor control of CINV in a preceding cycle and in patients who received the standard antiemetic therapy plus mirtazapine from their first cycle. A total of 35 patients were evaluated. Of these, 14 had poor control of CINV in a preceding cycle and received the standard antiemetic therapy plus mirtazapine in the next cycle. The rate of complete response in the delayed period in these patients was significantly improved from the preceding cycle to the next cycle (35.7% vs. 85.7%, p=0.018). In contrast, the other 21 patients had received the standard antiemetic regimen plus mirtazapine from the first cycle. The rate of complete response in the delayed period in these patients receiving the triplet antiemetic regimen plus mirtazapine as part of a cisplatin-based or carboplatin-based regimen and in patients receiving a doublet antiemetic regimen plus mirtazapine in a carboplatin-based regimen was 100%, 85.7% and 100%, respectively. No severe adverse events, including somnolence, were observed with the addition of mirtazapine. The addition of mirtazapine to the standard antiemetic regimen for CINV may be beneficial with acceptable safety when administered in association with platinum-based regimens to patients with thoracic cancer.

Exploratory analysis of the effect of a dexamethasone-sparing regimen for prophylaxis of cisplatin-induced emesis on food intake (LUNG-NEPA study)

We demonstrated the non-inferiority of a dexamethasone (DEX)-sparing (single-dose) regimen with NEPA, a netupitant/palonosetron fixed combination, for preventing chemotherapy-induced nausea and vomiting (CINV) caused by cisplatin. This pre-planned exploratory analysis assessed the effect of the DEX-sparing regimen on a patient’s food intake. Chemotherapy-naïve patients undergoing cisplatin (≥ 70 mg/m2) were given NEPA and DEX (12 mg) on day 1 and randomized to receive either no further DEX (DEX1), or oral DEX (4 mg BID) on days 2–4 (DEX4). Patient-reported endpoint maintenance of usual daily food intake was assessed during the 5-days post-chemotherapy. The relationship between usual daily food intake and CINV control, pre-chemotherapy self-rated food intake and BMI-adjusted weight loss (WL) were evaluated. One-hundred fifty-two patients (76/group) were assessable. The proportion of patients reporting maintenance of usual daily food intake was similar in both groups: 69.7% (95% CI, 58.6–78.9) for DEX1 vs. 72.4% (95% CI, 61.4–81.2) for DEX4. Only CINV control was significantly associated with maintenance of usual daily food intake (P ≤ 0.001) during the overall phase. The DEX-sparing regimen does not adversely affect patient-reported daily food intake post-chemotherapy. The current analysis adds further insights into antiemetic efficacy of DEX sparing beyond day 1 in the challenging setting of cisplatin.Trial registration: The parent study was registered on ClinicalTrials.gov (NCT04201769).

Efficacy and safety of low doses of olanzapine for the prevention of nausea and vomiting in children and adolescents receiving highly emetogenic chemotherapy. The interim results of a randomized trial

International studies and the analysis of our own data demonstrate that the standard three-drug (5-HT3 receptor antagonist, aprepitant and dexamethasone) regimen used for the prevention of chemotherapy-induced nausea and vomiting (CINV) gives the possibility to achieve complete CINV control in less than 50% of children receiving highly emetogenic chemotherapy. According to the results of randomized trials in adult patients, the addition of low doses of olanzapine increases the efficacy of CINV prophylaxis. There is no data on the efficacy and safety of low-dose olanzapine used for the prevention of CINV in children. The aim of this study is to assess the efficacy and safety of adding low doses (0.07 mg/kg, maximum 5 mg) of olanzapine to the standard regimen used for CINV prophylaxis after highly emetogenic chemotherapy in children. The study includes patients receiving highly emetogenic chemotherapy at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation, in case of which there are no other (except for chemotherapy) obvious reasons for nausea and vomiting and no contraindications for the use of olanzapine. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation, and registered in the US National Library of Medicine clinical trials registry (http://clinicaltrials.gov), the identification number is NCT05346731. Patients were randomized in a 1:1 ratio and stratified (previously received highly emetogenic therapy or not; regimens with high doses of cisplatin/carboplatin and without it) to receive the first cycle of highly emetogenic chemotherapy with standard three-drug prophylaxis with the addition of low doses of olanzapine or without it. Then, the patients underwent a second similar cycle of highly emetogenic chemotherapy with a change in the antiemetic prophylaxis option (crossover). For the assessment of CINV, we used the Pediatric Nausea Assessment Tool (PeNAT). Adverse events were assessed using CTCAE v.5.0. This is an interim analysis and it was carried out in order to assess whether it was reasonable to continue the study. From March to August 2022, 31 patients were included in the study, the median age was 14 (5–18) years, the ratio of boys:girls was 15:16; all patients suffered from extracranial solid tumors. Considering crossover, 31 patients included in the study received 62 cycles of chemotherapy (31 cycles with olanzapine and 31 cycles without it). Out of 31 cycles of chemotherapy with standard three-drug prophylaxis, complete CINV control was achieved in 16 (52%) cases, out of 31 cycles with prophylaxis, which included low doses of olanzapine – in 24 (77%) cases (p = 0.027). Adverse events associated with olanzapine were quite common (sedation - 97%, weight gain -76%), but mild (&lt; Grade III). According to the patient survey results, 30/31 (97%) patients preferred the regimen with olanzapine, and only 1 patient preferred neither of the regimens. The interim analysis of the study results shows that the addition of low doses of olanzapine significantly increases the efficacy of CINV prophylaxis in pediatric patients receiving highly emetogenic chemotherapy, is well tolerated, safe and preferred by the vast majority of patients. It is necessary to continue the study until the planned number of patients for the final analysis is included.

The emerging role of olanzapine in paediatric CINV control: A review.

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.

ЭФФЕКТИВНОСТЬ СТАНДАРТНОЙ ПРОФИЛАКТИКИ ТОШНОТЫ И РВОТЫ У ДЕТЕЙ, ПОЛУЧАЮЩИХ ВЫСОКОЭМЕТОГЕННУЮ ХИМИОТЕРАПИЮ: ДАННЫЕ РЕАЛЬНОЙ КЛИНИЧЕСКОЙ ПРАКТИКИ

The chemotherapy-induced nausea and vomiting (CINV) are of the most difficult to tolerate, often distressing, complications from a patient's point of view. Despite the success of modern antiemetic therapy this problem is far from being solved and the real effectiveness of antiemetic prophylaxis in children in Russia has not been studied as yet. The purpose of the study was to evaluate the effectiveness of routine CINV prevention against the highly emetogenic chemo in real clinical practice. Materials and methods of the study: the study included 88 patients aged 5 to 18 years old who received treatment from October, 2020, till June, 2021. The median age of patients was 14 [12.5-16] years old; the boys/girls ratio was 53%/47%. During the observation period the studied patients received 456 cycles of highly emetogenic chemo - Me (Q1-Q3) 5 (3-7). All of the patients included in this single-center prospective cohort study have received a standard three-component prophylaxis regimen that consisted of aprepitant, dexamethasone and a 5HT-3 receptor blocker on days of cytostatic therapy. Nausea and vomiting were assessed using the MASCC Antiemesis Tool (MAT) questionnaire and Baxter Retching Faces (BARF) and Pediatric Nausea Assessment Tool (PeNAT) graphic scales. Results: thanks to the use of the standard antiemetic prophylaxis the total control of CINV was achieved in 312 (68%), 239 (52%) and 198 (43%) cycles in the acute, delayed and general periods, respectively. The factors that were statistically significantly associated with an increase in the incidence of CINV were as follows: multi-day chemo regimens (p=0.016), high doses of cisplatin or carboplatin in the treatment regimen (p&lt;0.001) and anticancer therapy for a solid tumor (p=0.002). The presence of vomiting at the previous stage of cytostatic treatment also statistically significantly increased the incidence of CINV (p&lt;0.001). Conclusion: against the background of standard antiemetic prophylaxis more than a half of all the children receiving highly emetogenic cytostatic therapy continue to suffer from CINV. This requires the development and implementation of a modern, more effective approaches to the CINV prevention. The risk factors for the development of CINV identified in the study could be of help in further studies in order to stratify patients into groups. The fact of a significant increase in the risk of CINV development in patients who experienced these complications during initial therapy indicates the need for the most effective prevention of CINV from the very first cycle of treatment.

Interventions for the prevention of acute phase chemotherapy-induced nausea and vomiting in adult and pediatric patients: a systematic review and meta-analysis.

To identify effective and safe interventions to prevent acute phase chemotherapy-induced nausea and vomiting (CINV) in adult and pediatric patients. We conducted a systematic review of randomized trials evaluating interventions to prevent acute CINV. Outcomes assessed were complete chemotherapy-induced vomiting (CIV) control, complete chemotherapy-induced nausea (CIN) control, complete CINV control, and discontinuation of antiemetics due to adverse effects. The search identified 65,172 citations; 744 were evaluated at full-text, and 295 (25 pediatric) met eligibility criteria. In patients receiving highly emetogenic chemotherapy (HEC), complete CIV (risk ratio (RR) 1.23, 95% confidence interval (CI) 1.05-1.44) and CIN (RR 1.34, 95% CI 1.10-1.62) control improved when olanzapine was added. The addition of a neurokinin-1 receptor antagonist (NK1RA) to a corticosteroid plus a serotonin-3 receptor antagonist (5HT3RA) also improved complete CIV (RR 1.11, 95% CI 1.08-1.14) and CIN (RR 1.05, 95% CI 1.01-1.08) control. Compared to granisetron/ondansetron, palonosetron provided improved complete CIV control when the 5HT3RA was given alone or when combined with dexamethasone. In patients receiving moderately emetogenic chemotherapy (MEC), dexamethasone plus a 5HT3RA improved complete CIV control compared to a 5HT3RA alone (RR 1.29, 95% CI 1.21-1.39). Only a single meta-analysis evaluating the safety outcome was possible. For patients receiving HEC, various antiemetic regimens improved CIV and CIN control. For patients receiving MEC, administration of a 5HT3RA plus dexamethasone improved CIV control. Analysis of antiemetic safety was constrained by lack of data.