Prophylactic Antiemetic Regimens Research Articles

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.

Adherence to antiemetic guidelines in solid cancer patients receiving highly emetogenic chemotherapy in Korea.

Highly emetogenic chemotherapy (HEC) is known to induce nausea and vomiting (CINV) in approximately 90% of cancer patients undergoing this regimen unless proper prophylactic antiemetics are administered. This study aimed to analyze the use of a three-drug prophylactic antiemetic regimen during the first cycle of chemotherapy and assess the compliance rate with the National Comprehensive Cancer Network (NCCN) guidelines. This retrospective study utilized data from the National Inpatient Sample database from 2016 to 2020 provided by the Health Insurance Review and Assessment Service. The claims data encompassed 10 to 13% of inpatients admitted at least once each year. Patients with solid cancers treated with two HEC regimens, namely anthracycline + cyclophosphamide (AC) and cisplatin-based regimens, were selected as the study population. We evaluated the use of a three-drug prophylactic antiemetic regimen, including a neurokinin-1 receptor antagonist, a 5-hydroxytryptamine-3 receptor antagonist, and dexamethasone and compliance with the NCCN guidelines. Multiple logistic regression was conducted to estimate the influence of variables on guideline adherence. A total of 3119 patients were included in the analysis. The overall compliance rate with the NCCN guidelines for prophylactic antiemetics was 74.3%, with higher rates observed in the AC group (87.9%) and lower rates in the cisplatin group (60.4%). The AC group had a 6.37 times higher likelihood of receiving guideline-adherent antiemetics than the cisplatin group. Further analysis revealed that, compared to 2016, the probability of complying with the guidelines in 2019 and 2020 was 0.72 times and 0.76 times lower, respectively. This study showed that a considerable proportion of HEC-treated patients received guideline-adherent antiemetic therapies. However, given the variations in adherence rates between different chemotherapy regimens (AC vs. cisplatin), efforts to improve adherence and optimize antiemetic treatment remain essential for providing the best possible care for patients experiencing CINV.

Management of nausea and vomiting (N/V) following first-line (1L) zolbetuximab + chemotherapy treatment in claudin-18.2 (CLDN18.2)+, HER2−, locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma: Analysis from the phase 3 SPOTLIGHT and GLOW studies.

372 Background: The phase 3 SPOTLIGHT (NCT03504397) and GLOW (NCT03653507) studies showed clinically meaningful, statistically significant improvement in PFS and OS using 1L zolbetuximab + chemotherapy vs placebo (PBO) + chemotherapy in patients (pts) with CLDN18.2+, HER2−, LA unresectable or mG/GEJ adenocarcinoma. N/V were the most common treatment-emergent adverse events (TEAEs) reported in the zolbetuximab arm of these studies. We report an analysis of the incidence and management of N/V in SPOTLIGHT and GLOW. Methods: In SPOTLIGHT, pts (N = 565) were randomized 1:1 to zolbetuximab + mFOLFOX6 vs PBO + mFOLFOX6. In GLOW, pts (N = 507) were randomized 1:1 to zolbetuximab + CAPOX vs PBO + CAPOX. In both studies, neurokinin-1 receptor blockers (NK-1), selective serotonin receptor blockers (5-HT3), and other prophylactic antiemetic regimens were recommended to prevent and mitigate N/V per institutional care and guidelines. Results: A total of 279 pts in SPOTLIGHT and 253 pts in GLOW received zolbetuximab + chemotherapy. In SPOTLIGHT and GLOW combined, nausea occurred in 58% vs 18% of pts, and vomiting occurred in 43% vs 15% of pts in the first vs second zolbetuximab infusions, respectively; lower incidences of N/V were observed thereafter. During the first zolbetuximab infusion, the first episode of N/V occurred within 1 hour (median time, 48.0 min in SPOTLIGHT and 56.5 min in GLOW). Antiemetic usage and associated N/V rates are presented in the Table. The 96 pts in SPOTLIGHT and 52 pts in GLOW who had infusion modifications in cycle 1 due to TEAEs had numerically higher infusion rates than pts without infusion modifications; 85% of these modifications in SPOTLIGHT and 79% in GLOW were due to N/V. Zolbetuximab was discontinued within the first 9 weeks in 11 and 7 pts in SPOTLIGHT and 6 and 4 pts in GLOW due to nausea or vomiting, respectively. Conclusions: In SPOTLIGHT and GLOW, slower infusion rate and use of antiemetic combinations may have helped to mitigate N/V. These strategies will be important to support continued treatment and allow pts to achieve maximum clinical benefit with zolbetuximab + chemotherapy. Clinical trial information: NCT03504397 and NCT03653507 . [Table: see text]

2023 updated MASCC/ESMO consensus recommendations: prevention of nausea and vomiting following high-emetic-risk antineoplastic agents

PurposeThis systematic review updates the MASCC/ESMO recommendations for high-emetic-risk chemotherapy (HEC) published in 2016–2017. HEC still includes cisplatin, carmustine, dacarbazine, mechlorethamine, streptozocin, and cyclophosphamide in doses of > 1500 mg/m2 and the combination of cyclophosphamide and an anthracycline (AC) in women with breast cancer.MethodsA systematic review report following the PRISMA guidelines of the literature from January 1, 2015, until February 1, 2023, was performed. PubMed (Ovid), Scopus (Google), and the Cochrane Database of Systematic Reviews were searched. The literature search was limited to randomized controlled trials, systematic reviews, and meta-analyses.ResultsForty-six new references were determined to be relevant. The main topics identified were (1) steroid-sparing regimens, (2) olanzapine-containing regimens, and (3) other issues such as comparisons of antiemetics of the same drug class, intravenous NK1 receptor antagonists, and potentially new antiemetics. Five updated recommendations are presented.ConclusionThere is no need to prescribe steroids (dexamethasone) beyond day 1 after AC HEC, whereas a 4-day regimen is recommended in non-AC HEC. Olanzapine is now recommended as a fixed part of a four-drug prophylactic antiemetic regimen in both non-AC and AC HEC. No major differences between 5-HT3 receptor antagonists or between NK1 receptor antagonists were identified. No new antiemetic agents qualified for inclusion in the updated recommendations.

Portuguese consensus on the prevention and treatment of nausea and vomiting induced by cancer treatments.

Chemotherapy-induced nausea and vomiting (CINV) and radiotherapy-induced nausea and vomiting (RINV) strongly affect the quality of life of patients with cancer. Inadequate antiemetic control leads to the decline of patients' quality of life, increases rescue interventions, and may even compromise adherence to cancer treatment. Although there are international recommendations for controlling CINV and RINV, these recommendations focus mainly on pharmacological management, with scarce information on additional measures that patients may adopt. Moreover, the prophylaxis and management of CINV/RINV are not always applied. Thus, we identified the need to systematize the strategies for preventing and managing CINV/RINV and the associated risk factors to implement and promote effective prophylactic antiemetic regimens therapy in patients with cancer. This review sought to create a set of practical recommendations for managing and controlling CINV/RINV, according to the current international recommendations for antiemetic therapy and the main risk factors. Conclusively, we intended to produce a patient-centered guidance document for health care professionals focused on the awareness, monitoring, and treatment of CINV/RINV.

Olanzapine cost-effectiveness in vomiting and nausea from highly emetogenic chemotherapy in children and adolescents

ObjectivesTo assess the cost-effectiveness of addition of olanzapine to a prophylactic antiemetic regimen containing aprepitant, dexamethasone and ondansetron among children receiving highly emetogenic chemotherapy (HEC) in India, Bangladesh, Indonesia, the...

1673P Efficacy and safety of 5 mg olanzapine for the prevention of carboplatin-induced nausea and vomiting in patients with thoracic malignancies: A prospective multicenter phase II study

Carboplatin (CBDCA) is classified as a moderate emetic risk but is a higher risk than other chemotherapy agents. Therefore, a three-drug prophylactic antiemetic regimen is recommended comprising a 5-hydroxytryptamine type-3 receptor antagonist (5-HT3 RA), dexamethasone, and a neurokinin-1 receptor antagonist (NK1 RA). Olanzapine (OLZ) is lower cost than NK1 RA and more effective in controlling nausea. This phase II study aimed to investigate the efficacy and safety of a low dose of 5 mg OLZ in combination with 5-HT3 RA and dexamethasone for CBDCA-induced nausea and vomiting in patients with thoracic malignancies.

Abstract PS9-61: Incidence of intravenous (IV) hydration post anthracycline-cyclophosphamide (AC) chemotherapy in breast cancer patients

Abstract Background: Managing delayed chemotherapy-induced nausea and vomiting (CINV) associated with highly emetogenic chemotherapy (HEC) is an unmet need. AC-based HEC is often administered to breast cancer patients. The National Comprehensive Cancer Network and American Society of Clinical Oncology antiemetic guidelines recommend that if breakthrough CINV occurs, treatment should include an antiemetic agent from a different class not used in prophylaxis, as well as intravenous hydration and/or dexamethasone. The primary objective of this study is to retrospectively determine the incidence of IV hydration in post AC chemotherapy in breast cancer patients. Methods: The charts of 270 breast cancer patients receiving AC chemotherapy at University of Alabama at Birmingham (UAB) and on initial 3-drug prophylactic antiemetic regimens were retrospectively reviewed to determine the frequency, incidence, and timing of IV hydration. The hydration incidence was determined for 4 consecutive cycles of AC chemotherapy. The need for hydration was recorded post chemotherapy (e.g., nausea, vomiting, anorexia, loss of appetite, decreased oral intake). Physician and nurse chart notes were reviewed, including documented hydration visits post AC chemotherapy to outpatient infusion areas, local hospital emergency departments, or local hospital inpatient admissions. This report focuses on the patients who were on a guideline-recommended 3-drug regimen (palonosetron [Palo] + Neurokinin-1 [NK1] + dexamethasone [Dex], or ondansetron [Ond] + NK1 + Dex). These patients were followed and monitored for 4 consecutive cycles of AC chemotherapy, and the incidence of hydrations in different cycles was evaluated. Results: 270 patients were included in this analysis; 179 patients received Palo + NK1 + Dex (Group 1) and 91 patients received Ond + NK1 + Dex (Group 2) antiemetic regimens. Of the 179 patients in Group 1, 28 (16%) received hydration post chemotherapy, and 20 (22%) of the 91 patients in Group 2 received hydration (P=0.198, Chi-square test). Demographics and clinical characteristics of the 48 patients receiving hydration are presented in the Table. 28 patients in Group 1 had a total of 36 hydrations, the majority (20 [56%]) of which were in Cycle 1. 26/28 patients received rescue antiemetic treatment at the time of hydration, and 11 had a change in their prophylactic antiemetic regimen after hydration in subsequent chemotherapy cycles. Similarly, in Group 2, 20 patients had a total of 25 hydrations, with the majority (13 [52%]) in Cycle 1. 19 patients received rescue antiemetic treatment at the time of hydration, and 10 had a change in their prophylactic antiemetic regimen in subsequent chemotherapy cycles. Conclusions: The incidence of IV hydration post chemotherapy in breast cancer patients following AC-based HEC regimens occurred predominantly in the first cycle. Unscheduled hydrations, which occur when patients require evaluation in the clinic, and/or emergency department, may be complementary events for breakthrough measurement in CINV and could serve as a surrogate of associated healthcare utilization costs. Further clinical trials may consider evaluating unscheduled hydrations rates as part of a composite complete response endpoint (no breakthrough, no rescue medication, no unscheduled hydration). Table: Demographic and Antiemetic Regimens for Patients Requiring Post-chemo HydrationGroup 1Group 2Palo + NK1 + DexOnd + NK1 + Dex(n=179)(n=91)Post-chemo hydration, n (%)28 (16)20 (22)Demographics and Clinical Characteristics of Patients with Post-chemo Hydration (n=48)Median age, years (range)s56 (35-73)58 (33-70)Sex, n (%)Female27 (96)20 (100)Male1 (4)0ECOG Performance Status, n (%)015 (53)12 (60)112 (43)7 (35)201 (5)Unknown1 (4)0IV access, n (%)Central26 (93)20 (100)Peripheral2 (7)0Antiemetic Regimens Prior to Chemotherapy and Hydration RequirementsTotal number of patients requiring hydration, n (%)28 (16)20 (22)Total number of hydrations, n3625Number of hydrations in Cycle 1, n (%)20 (56)13 (52)Visits, n (%)Office16 (57)12 (60)Emergency department12 (43)8 (40)Rescue antiemetic(s) at time of hydration, n (%)26 (93)19 (95)Prophylactic antiemetic regimen switched, n (%)11 (39)10 (50)Dex = dexamethasone; ECOG = Eastern Cooperative Oncology Group; IV = intravenous;NK1 = Neurokinin-1; Ond = ondansetron; Palo = palonosetron. Citation Format: Rudolph M. Navari, Michael C. Mosier. Incidence of intravenous (IV) hydration post anthracycline-cyclophosphamide (AC) chemotherapy in breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-61.

Enhanced recovery after surgery (ERAS) program for lumbar spine fusion

BackgroundThere is a paucity of literature regarding the implementation of enhanced recovery after surgery (ERAS) protocols for open lumbar spine fusions. We implemented an ERAS program for 1–2-level lumbar spine fusion surgery and identified areas that might benefit from perioperative interventions to improve patient satisfaction and outcomes.MethodsThis institutionally approved quality improvement (QI) ERAS program for lumbar spine fusion was designed for all neurosurgical patients 18 years and older scheduled for 1 or 2 level primary lumbar fusions. The ERAS bundle contained elements such as multimodal analgesia including preoperative oral acetaminophen and gabapentin, postoperative early mobilization and physical therapy, and a prophylactic multimodal antiemetic regimen to decrease postoperative nausea and vomiting. No fluid management or hemodynamic parameters were included. Pre-ERAS and post-ERAS data were compared with regard to potential confounders, compliance with the ERAS bundle, and postoperative outcomes.ResultsA total of 230 patients were included from October 2013 to May 2017. The pre-ERAS phase consisted of 123 patients, 11 patients during the transition period, and 96 serving as post-ERAS patients. The pre-ERAS and post-ERAS groups had comparable demographics and comorbidities. Compliance with preoperative and intraoperative medication interventions was relatively good (~ 80%). Compliance with postoperative elements such as early physical therapy, early mobilization, and early removal of the urinary catheter was poor with no significant improvement in post-ERAS patients. There was no significant change in the amount of short-acting opioids used, but there was a decrease in the use of long-acting opioids in the post-ERAS phase (14.6 to 5.2%, p = 0.025). Post-ERAS patients required fewer rescue antiemetic medications in the recovery room compared to pre-ERAS patients (40 to 24%). There was no significant difference in postoperative pain scores or hospital length of stay between the two groups.ConclusionsImplementing an ERAS bundle for 1–2-level lumbar fusion had minimal effect in decreasing length of stay, but a significant decrease in postoperative opioid and rescue antiemetic use. This ERAS bundle showed mixed results likely secondary to poor ERAS protocol compliance. Going forward, this QI project will look to improve post-operative ERAS implementation to improve patient outcomes.

1792P - Comparison of palonosetron and granisetron in triplet antiemetic therapy in nonmetastatic breast cancer patients receiving high emetogenic chemotherapy. A multicenter, prospective, and observational study

We aimed to investigate the efficacy of 0.25 mg dose of palonosetron and granisetron in triplet antiemetic prophylaxis in breast cancer patients receiving HEC. Patients with nonmetastatic breast cancer who received HEC [doxorubicin or epirubicin plus cyclophosphamide (AC/EC)] were enrolled in the study. The prophylactic triplet antiemetic regimens were used according to the doctor’s preference during the first cycle of HEC as intravenous dexamethasone and palonosetron 0.25 mg or granisetron 3 mg on day 1 as well as oral aprepitant (125 mg on day 1 and 80 mg on days 2 and 3).The primary endpoint was complete response rate (CR) on acute and delayed chemotherapy-induced nausea and vomiting (CINV), separately. A total of 118 female patients were included in the study. Patients received AC (83%), EC (3%), and dose-dense AC (14%) as adjuvant (88%) or neoadjuvant (12%). The majority of patients received palonosetron (59%) containing antiemetic treatment. The CR rate on acute and delayed vomiting was very high and not statistically different in both of the arms (acute 87% vs. 96%, p = 0.089; delayed 90% vs. 92%, p = 0.489), respectively. Nevertheless, the CR rate on either acute or delayed nausea was lower than vomiting (acute 51% vs. 51%; delayed 38% vs. 29%, p = 0.203; respectively). This is the second study that compared a 0.25 mg dose of palonosetron with first-generation setron in triplet antiemetic prophylaxis in cancer patients receiving HEC. We could not find meaningful statistical differences between two arms, regarding CR rate on acute and delayed CINV.

A Randomized, Double-Blind, Placebo-Controlled Trial of Intravenous Acetaminophen on Hospital Length of Stay in Obese Individuals Undergoing Sleeve Gastrectomy.

Retrospective studies indicate that acetaminophen iv administration reduces hospital length of stay (LoS) and opiate consumption in patients undergoing bariatric surgery. This study sought to determine whether using acetaminophen iv in morbidly obese subjects undergoing sleeve gastrectomy decreased LoS and total hospital charges as compared to patients receiving saline placebo. Single-center university hospital METHODS: Using a randomized, double-blind, placebo-controlled design, subjects were assigned to receive either acetaminophen iv (group A) or saline placebo iv (group P). Data were collected between Jan 1 and Dec 31, 2016. Group A received acetaminophen every 6h for a total of four doses. The first dose was administered following the induction of general anesthesia; group P received saline iv on the same schedule. Anesthetic management and prophylactic antiemetic regimen were standardized in all subjects. Postoperative pain management consisted of hydromorphone via patient-controlled infusion pump. Primary outcomes include hospital LoS and associated hospital costs. Secondary outcomes include patient satisfaction and postoperative nausea and pain scores. Subject demographics (n = 127) and intraoperative management were similar in the two groups. Across all subjects, median hospital LoS in group A (n = 63) was 1.87 vs. 1.97days in group P (n = 64) (p = 0.03, Wilcoxon rank-sum test). Postoperatively, daily quality-of-recovery (QoR-15) scores, narcotic consumption, and the use of rescue antiemetics were not significantly different between groups. Median hospital costs were as follows: group A, $12,885 vs. group P, $12,977 (n = 64). Acetaminophen iv may reduce hospital LoS in subjects undergoing sleeve gastrectomy.

Managing chemotherapy-induced nausea and vomiting in head and neck cancer patients receiving cisplatin chemotherapy with concurrent radiation.

The purpose was to retrospectively examine the anti-emetic regimens prescribed for prophylaxis of chemotherapy-induced nausea and vomiting (CINV) for head and neck cancer patients receiving moderate- or high-emetogenic chemotherapy (MEC/HEC) along with concurrent radiation treatment at an outpatient ambulatory care center to determine the efficacy of anti-emetics prescribed. Consecutive patients with head and neck cancers who initiated cisplatin chemotherapy with concurrent radiation treatment between January 2013 and June 2015 were investigated. Patients' anti-emetic use and occurrence of CINV was extracted from available clinical documentation. Patients were divided into two cohorts: CISPL-HIGH (n=161), and CISPL-WEEKLY (n=38). A total of 199 head and neck cancer patients (158 male, 41 female) were included in the analysis (mean age =59 years). In the CISPL-HIGH cohort, 33 males (26%) and 16 females (49%) experienced CINV. In the CISPL-WEEKLY cohort, four males (13%) and two females (25%) experienced CINV. Nausea occurred in 71 patients (62 HEC and 9 MEC). The odds of achieving complete response (no nausea or vomiting) were 3.5 (P<0.0016) times more likely for patients receiving MEC. Overall, the complete response rate for the prophylaxis in MEC and HEC was 61% and 31%, respectively. Anti-emetic changes occurred in 34% and 11% of patients receiving HEC and MEC, respectively. In the current study CINV control for patients receiving HEC was sub-optimal. Changes to our prophylactic antiemetic regimens may help improve patient outcomes.

Emesis and nausea related to single agent trabectedin in ovarian cancer patients: a sub-study of the MITO15 project.

The MITO 15 was a prospective, single-arm trial, evaluating trabectedin monotherapy in patients with recurrent ovarian cancer (OC) who were BRCA mutation-carriers or had a BRCAness phenotype. It is largely reported that trabectedin may induce nausea and vomiting but the real emetogenic potential of the drug, in the different schedules, has never been fully described; furthermore, OC patients are known to have an enhanced risk of developing nausea and vomiting due to female gender, abdominal spreading of the disease, and major surgery experienced by most of them. We thought to carry on a sub-study in the MITO 15 context focused on chemotherapy-induced nausea and vomiting (CINV) associated with trabectedin single agent. For all patients enrolled in the trial, we evaluated the antiemetic regimen at the first cycle, acute and delayed CINV, any rescue therapy, any change in the prophylactic antiemetic regimen, and the potential relationship between dexamethasone dosage and incidence of CINV. Overall, our findings were consistent with literature and confirmed that trabectedin can be classified as moderately emetogenic. We observed slightly higher rates of both nausea and vomiting compared to previous experiences with trabectedin monotherapy, probably due to intrinsic features of our population: all females and suffering from ovarian cancer. It seems that in preventing acute CINV, the combination of three drugs was more effective than the doublet; however, the difference did not reach statistical significance; further studies are required to verify such hypothesis. Given the extreme heterogeneity of the antiemetic regimens used, it appears that a standard antiemetic protocol does not exist and more specific guidelines for clinicians are needed.

Treatment of Breakthrough and Refractory Chemotherapy-Induced Nausea and Vomiting.

Despite significant progress in the prevention of chemotherapy-induced nausea and vomiting (CINV) with the introduction of new antiemetic agents, 30–50% of patients receiving moderately or highly emetogenic chemotherapy (MEC or HEC) and guideline directed prophylactic antiemetics develop breakthrough CINV. International guidelines recommend the treatment of breakthrough CINV with an agent from a drug class that was not used in the prophylactic antiemetic regimen and recommend using the breakthrough medication continuously rather than using it on an as needed basis. There have been very few studies on the treatment of breakthrough CINV. A recent double-blind, randomized, phase III study suggested that olanzapine may be an effective agent for the treatment of breakthrough CINV. Refractory CINV occurs when patients develop CINV during subsequent cycles of chemotherapy when antiemetic prophylaxis has not been successful in controlling CINV in earlier cycles. Patients who develop refractory CINV should be considered for a change in their prophylactic antiemetic regimen. If significant anxiety exists, a benzodiazepine may be added to the prophylactic regimen. If a refractory patient is receiving HEC, olanzapine may be added to the prophylactic regimen. If the patient is receiving MEC, olanzapine or an NK-1 receptor antagonist may be added to the prophylactic regimen.

Phenothiazine vs 5HT3 antagonist prophylactic regimens to prevent Post-Anesthesia Care Unit rescue antiemetic: an observational study.

Our practitioners are asked to consider a patient's postoperative nausea and vomiting (PONV) risk profile when developing their prophylactic antiemetic strategy. There is wide variation in employed strategies, and we have yet to determine the most effective PONV prophylactic regimen. The objective of this study is to compare prophylactic antiemetic regimens containing: phenothiazines to 5HT3 antagonists for effectiveness at reducing the incidence of Post-Anesthesia Care Unit (PACU) rescue antiemetic administration. This is an observational study of 4,392 nonsmoking women who underwent general anesthesia for breast surgery from 1/1/2009 through 6/30/2012. Previous history of PONV or motion sickness (HxPONV/MS) and the use of PACU opioids were recorded. Prophylactic antiemetic therapy was left to the discretion of the anesthesia care team. We compared phenothiazines and 5HT3 antagonists alone and with a glucocorticoid to determine the most effective treatment regimen in our practice for the prevention of the administration of PACU rescue antiemetics. Patients who received a phenothiazine regimen compared to a 5HT3 antagonist regimen were less likely to have an antiemetic administered in the PACU (p=0.0100) and this significant difference in rates holds in a logistic regression model adjusted for HxPONV/MS and PACU Opioid use (p=0.0103). Based on our findings our clinicians are encouraged to administer a combination of a phenothiazine and a glucocorticoid in female, nonsmoking surgical breast patients for the prevention of PACU rescue antiemetic administration.

Prevention of Nausea and Vomiting in Patients Undergoing Oral Anticancer Therapies for Solid Tumors.

Chemotherapy-induced nausea and vomiting (CINV) is still a common and debilitating side effect despite recent advances in its prevention and treatment. The intrinsic emetogenicity of chemotherapy agents allowed grouping into four risk groups (high, moderate, low, and minimal risk of emetogenicity). The prevention of acute and delayed CINV for intravenous agents and one day regimens is well studied, although, there are few data about management of CINV induced by oral cytotoxic agents and targeted therapies, usually administered in extended regimens of daily oral use. Until now treatment of nausea and vomiting caused by oral antineoplastic agents remains largely empirical. The level of evidence of prophylactic antiemetics recommended for these agents is low. There are differences in the classification of emetogenic potential of oral antineoplastic agents between the international guidelines and different recommendations for prophylactic antiemetic regimens. Herein we review the evidence for antiemetic regimens for the most used oral antineoplastic agents for solid tumors and propose antiemetic regimens for high to moderate risk and low to minimal risk of emetogenicity.

Risk of severe and refractory postoperative nausea and vomiting in patients undergoing diep flap breast reconstruction

Postoperative nausea and vomiting (PONV) are commonly feared after general anesthesia and can impact results. The primary aim of our study was to examine incidence and severity of PONV by investigating complete response, or absence of PONV, to prophylaxis used in patients undergoing DIEP flaps. Our secondary aims were definition of the magnitude of risk, state of the art of interventions, clinical sequelae of PONV, and interaction between these variables, specifically for DIEP patients. A retrospective chart review occurred for 29 patients undergoing DIEP flap breast reconstruction from September 2007 to February 2008. We assessed known patient and procedure-specific risks for PONV after DIEPs, prophylactic antiemetic regimens, incidence, and severity of PONV, postoperative antiemetic rescues, and effects of risks and treatments on symptoms. Three or more established risks existed in all patients, with up to seven risks per patient. Although 90% of patients received diverse prophylaxis, 76% of patients experienced PONV, and 66% experienced its severe form, emesis. Early PONV (73%) was frequent; symptoms were long lasting (average 20 hours for nausea and emesis); and multiple rescue medications were frequently required (55% for nausea, 58% for emesis). Length of surgery and nonsmoking statistically significantly impacted PONV. We identify previously undocumented high risks for PONV in DIEP patients. High frequency, severity, and refractoriness of PONV occur despite standard prophylaxis. Plastic surgeons and anesthesiologists should further investigate methods to optimize PONV prophylaxis and treatment in DIEP flap patients.

A retrospective review of antiemetic use for chemotherapy-induced nausea and vomiting in pediatric oncology patients at a tertiary care center

Chemotherapy-induced nausea and vomiting are the most dreaded and distressing side effects for cancer patients undergoing chemotherapy treatment. These side effects have a significant impact on the patients' quality of life and can interfere with their ability to receive intensive chemotherapy regimens. With the recent advances in antiemetic pharmacotherapy and supportive care, the current treatments for chemotherapy-induced nausea and vomiting, when used appropriately, have become highly effective in mitigating these adverse effects. The aim of this study was to evaluate the current practice involving antiemetic treatment in newly diagnosed pediatric oncology patients at our center. This was a retrospective cohort study of newly diagnosed pediatric oncology patients who were less than 14 years of age receiving their first cycle of inpatient chemotherapy. The data abstracted included the following: age, gender, type of cancer, chemotherapy regimen, emetogenic risk and level, prescribed prophylactic antiemetic regimen, incidence of breakthrough emesis, and breakthrough antiemetic medications used. Emetogenic risk was classified based on published guidelines into low, moderate, or high emetogenic chemotherapy, and a scoring system to determine the emetogenic level of combined chemotherapy agents was followed to monitor the efficacy of the antiemetic regimens. Clinical effectiveness was assessed based on breakthrough emesis. A total of 49 patients were eligible for the study. High emetogenic chemotherapy was administered in 28/49 (57.1%) and moderate emetogenic chemotherapy was administered in 21/49 (42.9%) patients. Only 10/49 (20.4%) received appropriate antiemetic prophylaxis, whereas 39/49 (79.6%) received inadequate antiemetic prophylaxis; 14/49 (28.6%) patients experienced breakthrough emesis. Breakthrough emesis occurred in 11/28 (39.3%) patients receiving high emetogenic chemotherapy and 3/21 (14.3%) patients receiving moderate emetogenic chemotherapy. The use of an inadequate antiemetic regimen was found in 14/14 (100%) patients with breakthrough emesis. Thus, inadequate prophylaxis resulted in a 35.9% (14/39) risk of breakthrough emesis. This risk was higher in patients receiving high emetogenic chemotherapy versus those receiving moderate emetogenic chemotherapy (39.3% versus 14.3%). Inadequate antiemetic prophylaxis is associated with a high risk of breakthrough emesis particularly with high emetogenic chemotherapy regimens. Standardizing antiemetic prophylaxis based on emetogenic level could reduce breakthrough emesis and improve the quality of life in pediatric oncology patients.

„Low-dose“-Droperidol-Gabe bei Kindern

Droperidol had been used as an effective antiemetic since the 1970s but was withdrawn from the market in 2001 because of a black box warning about QT prolongation and possible cardiac arrhythmia after high doses. In the meantime the black box warning has seriously been questioned and parenteral droperidol has again been licensed in 2008. Because droperidol acts on dopaminergic receptors different to 5-HT(3) antagonists and dexamethasone, it could possibly serve as a rescue drug after failed postoperative nausea and vomiting (PONV) prophylaxis. Persistent PONV after the recommended prophylaxis is a significant problem in pediatric anesthesia but a satisfactory strategy has not yet been defined. Therefore a retrospective audit was performed in order to evaluate whether low-dose droperidol (10 µg/kgBW) would be an effective rescue drug for failed antiemetic prophylaxis.The electronic anesthesia patient data base of the University Children's Hospital Zurich was searched from 2004-2009 for patients who received low-dose droperidol in the postanesthesia care unit as rescue therapy for persistent PONV after antiemetic prophylaxis. Based on the recorded electronic data the effectiveness of low-dose droperidol as PONV rescue therapy and possible side effects were analyzed.A total of 338 patients who received droperidol were found from a total of 34,032 patients and the charts were analyzed. Of these patients 134 were excluded because they had received droperidol for indications other than PONV, 43 patients were excluded because they had not received antiemetic prophylaxis before droperidol and in 17 patients the data were incomplete, leaving 144 patients with an average age of 12.3 years (interquartile range IQR 9.5-15.2 years) for analysis. The upper range of ages resulted from patients with chronic diseases who were still being treated in the Children's Hospital. Low-dose droperidol was given because of persistent nausea to 59 patients (41%) and to 85 patients (59%) for persistent vomiting. Initial antiemetic prophylaxis and/or therapy had consisted of dexamethasone plus tropisetrone in 80 patients and tropisetrone or dexamethasone alone in 64 patients. In 128 patients (89%) rescue therapy with a median dose of 10.9 µg/kgBW droperidol was effective but vomiting persisted in 16 patients (11%). Sedation was the only side effect recorded and this was observed in 39 patients (27%).Low-dose droperidol (10 µg/kgBW) was found to be effective as rescue medication in pediatric patients experiencing PONV despite various prophylactic antiemetic regimens. No neurological or cardiopulmonary side effects were recorded after this low dosage.

Impact of initiating antiemetic prophylaxis with palonosetron versus ondansetron on risk of uncontrolled chemotherapy-induced nausea and vomiting in patients with lung cancer receiving multi-day chemotherapy

The purpose of this study is to examine the risk of uncontrolled chemotherapy-induced nausea/vomiting (CINV) among lung cancer patients receiving multi-day chemotherapy and ondansetron- or palonosetron-initiated prophylactic antiemetic regimens in a community oncology setting. The Georgia Cancer Specialists electronic medical records database was used to retrospectively identify lung cancer patients who received multi-day cisplatin or carboplatin regimens with ondansetron or palonosetron on day 1 between April 1, 2006 and July 31, 2009. Uncontrolled CINV events were identified through ICD-9-CM codes (nausea/vomiting), CPT codes (dehydration), rescue medications, nausea/vomiting hospitalizations, and/or antiemetic therapy after last chemotherapy administration of the cycle. Risk for uncontrolled CINV, up to 7 days after last chemotherapy administration, was analyzed at cycle level using logistic regression with regressors of gender, age, number of chemotherapy administration days, Charlson comorbidity index, cancer type, multicancer diagnoses, and chemotherapy regimen. A total of 209 palonosetron and 153 ondansetron patients (702 and 515 cycles, respectively) met the inclusion criteria. Palonosetron patients were significantly older (mean 67.9 versus 63.9 years; P < 0.0001), with no significant difference in gender, baseline comorbidity score, or multicancer diagnosis. Palonosetron cycles had 63% lower risk for uncontrolled CINV events versus ondansetron cycles [odds ratio (OR) 0.37; 95% confidence interval (CI) 0.25-0.54; P < 0.0001]. Sub-analysis by chemotherapy supported overall analysis (cisplatin OR 0.09; 95% CI 0.04-0.25; P < 0.0001; carboplatin OR 0.46; 95% CI 0.30-0.70; P = 0.0003). In this retrospective analysis of lung cancer patients, multi-day chemotherapy cycles administered with palonosetron on day 1 were associated with a significantly lower risk for uncontrolled CINV events versus ondansetron-initiated chemotherapy cycles.