Highly Emetogenic Chemotherapy Regimens Research Articles

Dexamethasone-Sparing Antiemetic Prophylaxis for Chemotherapy-Induced Nausea and Vomiting in Highly and Moderately Emetogenic Chemotherapy: The SHEILD Study.

Chemotherapy-induced nausea and vomiting (CINV) significantly impacts patient's quality of life and treatment adherence. This study investigated the efficacy of Generic Netupitant and Palonosetron tablets (Nykron) with dexamethasone single dose for CINV prophylaxis in patients receiving highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC).Additionally, this approach aligns with the principles of the SHIELD study (Sparing High Efficacy Intervention for Low Dose Dexamethasone), which focuses on maximizing antiemetic effectiveness while minimizing dexamethasone use. This multicenter retrospective study evaluates data from patients who received HEC/MECand were administered a fixed-dose combination of Generic NEPA (Netupitant 300 mg and Palonosetron 0.5 mg tablets, Nykron combi-pack) along with a single dose of dexamethasone (12 mg/8 mg) before chemotherapy. The data were collected from September 2022 till September 2023. Outcomes measuredincluded complete response (no vomiting and no need for rescue medications), complete protection (no significant nausea (<2.5 cm on VAS), no vomiting, and no use of rescue medication), and complete control (no emetic episodes, no rescue therapy, and no nausea [0 cm on VAS])during the acute phase (0-24 hours) and delayed phase (24-120 hours) post-chemotherapy. The data of 372 patients was evaluated in which breast cancer was the most common cancer with 223 (59.95%) patients for which doxorubicin and cyclophosphamide (192, 51.61%) was the most administered chemotherapy combination. The second most common cancer was gastrointestinal (GI) cancer with stomach cancer in 47 (12.6%), colorectal cancer in 4 (1%), and pancreatic cancer in 2 (0.54%). A total of 360 (96.8%) patients received an HEC regimen across the cycle, while only 5 (1.3%) received an MEC regimen. The regimen demonstrated exceptional efficacy with a 96.9% overall response rate across all cycles. Complete control rates for acute CINV were 92% and 90% for delayed CINV across chemotherapy cycles. Complete response rates remained consistently high (94%-98%) across all cycles and overall phases. Only 3% of patients experienced anticipatory CINV. This dexamethasone-sparing Generic NEPA regimen showed remarkable efficacy in CINV management for HEC/MEC regimen-receiving patients, maintaining high response rates in both acute and delayed across all cycles. These findings indicate a potential paradigm shift in CINV prophylaxis, necessitating further investigation through prospective, randomized controlled trials to validate long-term safety and efficacy.

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.

Effectiveness of NEPA, an oral fixed-dose combination of netupitant and palonosetron in the prevention of chemotherapy induce nausea (CIN): A post-hoc analysis.

e24140 Background: Despite widespread use of antiemetics, chemotherapy-induced nausea is still reported by upto 70% of adult patients receiving moderately emetogenic chemotherapy(MEC) or highly emetogenic chemotherapy (HEC) agents. Control of nausea remains an important, unmet need among cancer patients. The current evidence suggests that, overall, no significant nausea is reported by upto 75% of the patients with the aprepitant based regimens. Here, we present a post-hoc analysis of an observational study on NEPA (NEtupitant 300mg and PAlonosetron 0.50 mg) in preventing nausea in patients receiving HEC/MEC in a real-world setting in India. Methods: An open-label, single-arm, prospective study among chemonaive patients was conducted across six centers from April 2019 to December 2021 after approval from each institutional ethics committee (CTRI/2020/02/023586). A post-hoc analysis was carried out to assess the effectiveness of NEPA in preventing CIN in patients. The parameters assessed included severity of nausea using a visual analogue scale (VAS) [No significant nausea (includes no/mild nausea) &lt; 2.5cm on VAS scale, moderate nausea 2.5cm to 7.5cm, Severe nausea 7.5cm to 10cm], complete control (no nausea and complete response) and safety. Results: Of the 354 patients, 289 (81.64%) received the HEC regimen, and the remaining 65 (18.36%) received the MEC regimen. Anthracycline-Cyclophosphamide (36.16%) and FOLFOX (6.21%) were the most common HEC and MEC regimens, respectively. In the overall, acute, and delayed phases, no significant nausea was reported in 89.83%., 93.22% and 92.65% of the patients, respectively. Moderate and severe nausea was reported in 5.65%, and 1.13% of patients in the acute phase, 5.65%, and 1.69% in the delayed phase, and 8.19%, and 1.98% in the overall phase respectively. Among, those on HEC and MEC regimen, no significant nausea was reported in 93.42 % and 89.23 % respectively during the overall phase (Table 1). Complete control was achieved in 77.40% of patients in the overall phase, 82.77% in the acute phase, and 85.03% in the delayed phase. Adverse events were reported in 10 (3.4%) patients, with leg pain being the most common 3(0.8%). Conclusions: NEPA was found to be effective and well tolerated in preventing nausea in patients receiving HEC/MEC regimens, with almost 90% of patients reporting no significant nausea in real world Indian setting. Clinical trial information: CTRI/2020/02/023586 .[Table: see text]

OLANZAPINE AS PROPHYLACTIC ANTIEMETIC IN BREAST CANCER PATIENTS: A PROSPECTIVE COMPARATIVE STUDY IN A TERTIARY CARE CENTRE

Context: Aims The prevention of chemotherapy induced nausea and vomiting (CINV) by olanzapine can improve patients adherence to treatment. and objectives: To study the efcacy of olanzapine as prophylactic antiemetic in parenteral highly emetogenic chemotherapy (HEC) regimen of breast cancer and to compare its side effects with aprepitant. Prospect Settings and Design: ive, comparative, open-label, non randomized study was conducted on 146 eligible breast cancer patients, equally distributed into aprepitant and olanzapine groups. The Methods and Material: Multinational Association of Supportive Care in Cancer (MASCC) Tool (MAT) and Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 was used for evaluation. Chi-square test and unpaired t test was applied to test for sta Statistical analysis used: tistical signicance using ©2021 GraphPad Prism. P value ≤ 0.05 was considered signicant. Data were represented using frequency distribution table and bar diagrams. Patients achieving Complete Response (CR, no emesis and no rescue me Results: dication) was signicantly higher in olanzapine treated group. Nausea was signicantly controlled but vomiting wasn't signicantly controlled with olanzapine when compared with aprepitant. Assessment of side effects showed signicantly increased sedation on day 2 on those receiving olanzapine in comparison to aprepitant. Conclusions: Olanzapine has signicant results in controlling CINV caused by parenteral HEC regimens when compared with aprepitant in acute, delayed and overall period with minimal increase in sedation

Effectiveness of NEPA, an oral fixed-dose combination of NEtupitant and PAlonosetron in the prevention of chemotherapy-induced nausea-vomiting in patient receiving highly emetogenic chemotherapy regimens.

e24090 Background: Patients receiving Highly Emetogenic chemotherapy (HEC) are &gt; 90% risk of nausea-vomiting due to the drug's emetogenic potential and patient-related factors such as young age, female gender, low/no alcohol, H/O morning sickness and use of alternative medications. The current study was designed to assess the effectiveness of NEPA in patients receiving HEC in a real-world setting in India. Methods: An open-label, single-arm, prospective study among chemonaive patients was conducted across six centers from April 2019 to December 2021 after approval from each institutional ethics committee (CTRI/2020/02/023586). Complete response and treatment-emergent adverse events were the primary endpoints. Secondary endpoints included completion protection, complete control and severity of nausea. Results: HEC regimens were prescribed in 289 of the 360 patients enrolled in the study. Most common HEC regimen was Anthracycline-Cyclophosphamide (44.2%) followed by Paclitaxel-Carboplatin (17.9%). Average age of study population was 52.8±9.8 yrs. with male: female ratio of 1:2.1. Hypertension (17.6%) and diabetes (12.4%) were common comorbidities. Complete response in acute, delayed and overall phases were 94.4%, 94.8%, and 92.7% respectively. In overall phase, complete protection and complete control was 86.8% and 77.5% respectively. Mild, moderate and severe nausea were reported in 11.7%, 7.6%, and 2.4%, patients respectively. Adverse events were seen in 10(3.4%) patients, with leg pain being the most common 3(0.8%). One serious adverse event, unrelated to the study drug was reported. Conclusions: NEPA was effective and well tolerated in patients on a HEC regimen in the acute, delayed and overall phases with a completed response rate of &gt; 90%. Clinical trial information: CTRI/2020/02/023586. [Table: see text]

The effectiveness of NEPA in the prevention of chemotherapy-induced nausea vomiting among chemo naive patients in an Indian setting

BackgroundChemotherapy induced nausea- vomiting (CINV) is considered as the most common, feared and most troublesome side effect of chemotherapy. NEPA (NEtupitant 300 mg + PAlonosetron 0.50 mg) is the first commercially available oral fixed-dose combination (FDC) of two active antiemetic agents in India. The present study was planned to evaluate the effectiveness of NEPA in the real world setting of India.MethodsThis was a multicentric retrospective study conducted in two centers in India. The data of all chemonaive patients, who were prescribed NEPA was analyzed. Effectiveness i.e. complete response and complete protection in controlling overall, acute and delayed phase was analyzed.ResultsA total of 329 patients were enrolled in the study. 260 received highly emetogenic chemotherapy (HEC) regimen and 69 received moderately emetogenic chemotherapy (MEC) regimen. Among all the enrolled patients, complete response in acute, delayed and overall phase was 93, 85.71 and 85.41% respectively; and completed protection was 88.44, 81.76 and 80.54% respectively. Those who received HEC regimen, the completed response and complete protection in overall phase was 84.61 and 79.61% respectively and those who received MEC regimen the completed response and complete control in overall phase was 84.05 and 84.05% respectively.ConclusionA single oral dose of NEPA targeting dual pathways showed effective control of nausea-vomiting in patients on the HEC and MEC regimens and had good control over nausea-vomiting in acute, delayed and overall phase of nausea-vomiting.

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.

Avoidable Acute Care Use Associated with Nausea and Vomiting Among Patients Receiving Highly Emetogenic Chemotherapy or Oxaliplatin.

Chemotherapy-induced nausea and vomiting (CINV) contributes to avoidable acute care, a metric now tracked in Medicare's oncology outcome measure. CINV is preventable, yet guidelines are often not followed. We sought to quantify acute care involving CINV and other avoidable toxicities after highly emetogenic chemotherapy (HEC) to identify excess risk and assess clinician adherence to antiemesis guidelines for HEC. We retrospectively evaluated U.S. electronic health records (2012-2018) using Medicare's OP-35 outcome measure to identify avoidable acute care involving any of 10 toxicities, including CINV, after HEC regimens relative to non-HEC. Antiemetic guideline adherence was defined as use ofneurokinin-1 (NKl) receptor antagonists Q5 (RAs) plus 5-hydroxytryptamine type 3 RA+ dexamethasone at HEC initiation. Among 17,609 patients receiving HEC, acute care rates associated with HEC chemotherapy included 32% cisplatin, 31% carboplatin, and 21% anthracycline/cyclosphospharnide (AC), with 76% meeting the criteria as avoidable events. Oxaliplatin rates were 29%. Avoidable acute care occurred 1.83 times (95% confidence interval, 1.76-1.91, p < .0001) as often after HEC versus non-HEC excluding oxaliplatin; CINV-related acute care occurred 2.29 times as often. Nonadherence to antiemesis guidelines occurred in 34% and 24% of cisplatin and AC courses, respectively, because of omission of a NKl RA. Patients treated with HEC regimens experienced high avoidable acute care use, 1.8 times the risk seen for other chemotherapy. Nonadherence to guideline-directed antiemetic prophylaxis highlights the need to ensure adherence to antiemetic guidelines, including the use of NKl RA in HEC. After survival, perhaps the most important goal in oncology is limiting avoidable acute care, a goal now used by Medicare to impact cancer reimbursement. This study found that patients treated with highly emetogenic chemotherapy (HEC) regimens had high rates of avoidable acute care use, 1.8 times the risk seen for other chemotherapy. A substantial proportion of the avoidable acute care involved chemotherapy-induced nausea and vomiting. Results showed that incomplete adherence to national antiemetic guidelines for HEC regimens primarily driven by omission of upfront neurokinin-1 receptor antagonist use, suggesting that improved adherence can meaningfully resolve this gap in quality and cost of care.

Study protocol for SPARED trial: randomised non-inferiority phase III trial comparing dexamethasone on day 1 with dexamethasone on days 1–4, combined with neurokinin-1 receptor antagonist, palonosetron and olanzapine (5 mg) in patients receiving cisplatin-based chemotherapy

IntroductionDexamethasone (DEX) is administered for multiple days to prevent chemotherapy-induced nausea and vomiting for patients receiving highly emetogenic chemotherapy (HEC); however, its notorious side effects have been widely reported. Although...

A retrospective case cohort analysis on the clinical utility of fosaprepitant in CINV prophylaxis in day care center of South India

Background: Control of chemotherapy-induced nausea and vomiting is a crucial factor in ensuring patient’s compliance and adherence to cancer chemotherapy cycle. Fosaprepitant is a water-soluble N-phosphoryl derivative of aprepitant, which is often administered along with 5-hydroxytryptamine 3 antagonist and a steroid in patients with highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Materials and Methods: A single-centric, retrospective cohort study was conducted in HCG Cancer Centre in South India, where patients who were prescribed fosaprepitant as a part of standard therapy were enrolled. Results: Among the 290 patients who were included in the analysis, 41.72% were male, 58.27% were female, and 36.20% belonged to 51–60 years of age. Advanced breast carcinoma was the most common diagnosis in 38.96% patients. HEC was prescribed in 222 patients; moderate emetogenic drugs and regimen were prescribed in 62 patients. Among patients who were prescribed HEC and MEC drugs and regimen, fosaprepitant, palonosetron, and dexamethasone were prescribed on day 1 followed by dexamethasone on days 2, 3, and 4. No infusion site reaction, hiccups, or any other adverse reactions were noted. Complete response was noted in all patients (100%) with HEC and MEC regimen cases. The formulation was well tolerated with none reporting any persistent or delayed or breakthrough emesis. Conclusion: Single-dose fosaprepitant used in combination with palonosetron and dexamethasone was well tolerated and effective in preventing chemotherapy-induced vomiting in patients receiving highly and moderately emetogenic drugs and regimen.

Economic analysis of palonosetron versus granisetron in the standard triplet regimen for preventing chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy in Japan (TRIPLE phase III trial)

BackgroundWe conducted an economic assessment using test data from the phase III TRIPLE study, which examined the efficacy of a 5-hydroxytryptamine 3 receptor antagonist as part of a standard triplet antiemetic regimen including aprepitant and dexamethasone in preventing chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based highly emetogenic chemotherapy (HEC).MethodsWe retrospectively investigated all medicines prescribed for antiemetic purposes within 120 h after the initiation of cisplatin administration during hospitalization. In the TRIPLE study, patients were assigned to treatment with granisetron (GRA) 1 mg (n = 413) or palonosetron (PALO) 0.75 mg (n = 414). The evaluation measure was the cost-effectiveness ratio (CER) assessed as the cost per complete response (CR; no vomiting/retching and no rescue medication). The analysis was conducted from the public healthcare payer’s perspective.ResultsThe CR rates were 59.1% in the GRA group and 65.7% in the PALO group (P = 0.0539), and the total frequencies of rescue medication use for these groups were 717 (153/413 patients) and 573 (123/414 patients), respectively. In both groups, drugs with antidopaminergic effects were chosen as rescue medication in 86% of patients. The costs of including GRA and PALO in the standard triplet antiemetic regimen were 15,342.8 and 27,863.8 Japanese yen (JPY), respectively. In addition, the total costs of rescue medication use were 73,883.8 (range, 71,106.4–79,017.1) JPY for the GRA group and 59,292.7 (range, 57,707.5–60,972.8) JPY for the PALO group. The CERs (JPY/CR) were 26,263.4 and 42,628.6 for the GRA and PALO groups, respectively, and the incremental cost-effectiveness ratio (ICER) between the groups was 189,171.6 (189,044.8–189,215.5) JPY/CR.ConclusionsWe found that PALO was more expensive than GRA in patients who received a cisplatin-based HEC regimen.

Chemotherapy-Induced Nausea and Vomiting (CINV) in Hematologic Malignancy Patients Receiving Multi-Day Highly Emetogenic Chemotherapy (HEC)

INTRODUCTIONDespite recent advances in CINV prophylaxis, many questions remain unanswered including optimal treatment for hematologic malignancy (HM) patients receiving multi-day chemotherapy regimens. As preparation for stem cell transplant (SCT) and for high grade HM, highly emetogenic chemotherapy (HEC) containing regimens are often utilized. International guidelines recommend a three-drug combination of a 5-HT3receptor antagonist (5-HT3 RA), an NK-1 receptor antagonist (NK-1 RA) and dexamethasone (dex) before HEC. Little is known about CINV prevention in HM multi-day regimens.METHODSWe conducted a prospective observational study in U.S. research centers with expertise in HM and SCT surveying providers and adult patients receiving up to 7 consecutive days of chemotherapy including at least one HEC drug. Those receiving concurrent radiation therapy were excluded as were patients taking antiemetics or having nausea and vomiting prior to initiation of chemotherapy. Patients completed a diary and a modified Functional Living Index - Emesis (FLIE) questionnaire daily, beginning at screening, during chemotherapy, and for up to 5 days after the last day of treatment. Daily use of scheduled antiemetics and rescue medication was collected. The primary objective was to survey patterns of CINV care for multi-day chemotherapy in HM and assess efficacy of the intervention.RESULTSSeventy-six patients were enrolled at 5 centers (range 8 -25 patients per center) between May 2015 and February 2016. Of the patients, 72 underwent pre-SCT conditioning and 4 multi-day chemotherapy for HM. Forty-nine (68%) were male and 58 (81%) were Caucasian; median age was 58 (range 22-74). The most common diagnoses were NHL, 27 (36%); multiple myeloma, 19 (25%); and AML, 15 (20%). Seventy-one patients completed all surveys. All received ≥ 1 HEC drug on day 1. The most common chemotherapy regimens were BEAM, 28 (37%), high-dose melphalan, 18 (26%), melphalan, fludarabine, and campath, 8 (11%) and fludarabine and cyclophosphamide, 4 (5%). Anti-emetic therapy was highly variable, both prior to day 1 chemotherapy and throughout multi-day treatment. On day 1 the most common regimens included: a combination of 5-HT3 RA, NK-1 RA, dex in 28 (37%); 5-HT3 RA + dex in 24 (32%); 5-HT3 RA alone in 9 (12%); 5-HT3 RA and metoclopramide in 2 (3%); other 10 (13%) and none documented 3 (4%). Complete response rate (defined as no vomiting and no use of rescue medications) was observed in 15 patients (20%); complete response by day ranged from 95% on day 1 to 46% on end of study day (p=0.041). Mean±SD nausea scores by FLIE increased from 19.9±3.1 pretreatment to 22.4±3.3 overall (p=0.0031).CONCLUSIONApproaches to CINV in SCT and HM patients receiving multi-day HEC regimens are highly variable. A large majority of patients receiving multi-day chemotherapy are not achieving adequate control of nausea or vomiting. Additional clinical trials and development of evidence-based approaches to CINV prophylaxis in HM patients throughout multi-day chemotherapy are critical to improve supportive care. DisclosuresSchwartzberg:Helsinn: Consultancy, Research Funding; Eisai: Consultancy; Tesaro: Consultancy; Heron: Consultancy. Roeland:Teva: Speakers Bureau; Insys: Consultancy; Helsinn: Consultancy; Heron: Consultancy; AstraZeneca: Consultancy, Research Funding; Eisai: Speakers Bureau.

Safety and efficacy of NEPA, an oral fixed combination of netupitant and palonosetron, in older patients.

Prevention of chemotherapy-induced nausea and vomiting is critical in older patients with cancer. NEPA is an oral fixed combination of netupitant 300mg, a new NK1 receptor antagonist (RA), and palonosetron 0.5mg, a pharmacologically distinct 5-HT3 RA. This retrospective analysis evaluated the efficacy and safety of NEPA in older patients. Patients aged ≥65 and ≥70years from one phase II and two phase III trials were considered. Chemotherapy-naive patients with malignant tumors were treated with anthracycline-cyclophosphamide (AC), non-AC-based moderately emetogenic chemotherapy (non-AC MEC), or highly emetogenic chemotherapy (HEC). Following single-dose NEPA, patients received oral dexamethasone on day 1 (AC and non-AC MEC) or days 1-4 (HEC). Efficacy was evaluated through complete response (CR) in cycle 1. Safety was evaluated by AEs and ECGs. Data were summarized by descriptive statistics. Overall, 214 patients were ≥65years and 80 were ≥70years. A higher CR was observed in older patients versus the total population; in the acute phase >90% of patients ≥65years experienced CR. Efficacy was maintained over multiple cycles of chemotherapy. No significant nausea rates were generally higher in the older patients versus total population. Similar rates of AEs in the first treatment cycle were reported for patients ≥65years, ≥70years, and total population (72.9% vs 67.5% vs 70.0%, respectively). No cardiac safety concerns were raised. NEPA is highly effective in older patients receiving MEC or HEC regimens. NEPA is also well tolerated, demonstrating suitability for use in older patients who may have comorbidities.

Clinical Practices and Outcomes on Chemotherapy-Induced Nausea and Vomiting Management in South Korea: Comparison with Asia-Pacific Data of the Pan Australasian Chemotherapy Induced Emesis Burden of Illness Study

PurposeThis study reported patient outcomes of chemotherapy-induced nausea and vomiting (CINV) prophylaxis for highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC) regimens and evaluated its adherence to acute-phase CINV prophylaxis in the Korean population subset of the Pan Australasian Chemotherapy Induced Emesis burden of illness (PrACTICE) study.Materials and MethodsThis subgroup analysis evaluated 158 Korean patients receiving HEC or MEC and compared the data (wherever possible) with that of 648 patients from the Asia-Pacific (AP) region. Study endpoints included evaluation of primary CINV prophylaxis and adherence to acute-phase CINV prophylaxis in cycle 1 (American Society of Clinical Oncology [ASCO] Quality Oncology Practice Initiative [QOPI]).ResultsIn South Korea and the AP, a 5-hydroxytryptamine-3 receptor antagonist (5HT3-RA) prophylaxis for the acute phase was administered to 79/80 patients (98.8%) for HEC and 70/71 patients (98.6%) for MEC regimens (QOPI-1). Triple regimen (corticosteroid–5HT3-RA–neurokinin 1-RA) was initiated in 46/80 patients (57.5%) for prophylaxis of acute CINV in cycle 1 of HEC (QOPI-3). Double regimen (corticosteroid–5HT3-RA, with or within NK1-RA) was initiated in 61/71 patients (83.1%) for control of acute CINV in cycle 1 of MEC a(QOPI-2).ConclusionActive management of CINV is necessary in cycle 1 of HEC in South Korea, despite higher rates than the AP region. Adherence to the international guidelines for CINV prophylaxis requires attention in the acute phase in cycle 1 of the HEC regimen.

Testing the effectiveness of antiemetic guidelines: results of a prospective registry by the CINV Study Group of Japan.

Many cancer patients suffer from the common side effect of chemotherapy-induced nausea and vomiting (CINV). Guidelines recommend a combination of two prophylactic antiemetics for moderately emetogenic chemotherapy (MEC) and three for highly emetogenic chemotherapy (HEC) and certain MEC regimens. This multicenter, prospective, observational study analyzed data for 1,910 patients in Japan scheduled for MEC or HEC. Use of antiemetic prophylaxis in relation to type of chemotherapy, incidences of and risk factors for nausea, vomiting, and acute versus delayed CINV, and estimated incidence of CINV by staff were analyzed using Fisher's exact test and multivariate logistic regression. The patients recorded the incidence of CINV and severity of nausea by visual analogue scales daily for 7 days after receiving chemotherapy. A total of 240 (20.1 %) HEC and 476 MEC patients (66.6 %) received 2 antiemetics, compared with 883 (73.9 %) and 200 (28.0 %), respectively, who received 3 antiemetics. Approximately 74 % of HEC and 95 % of MEC patients received antiemetic therapy in compliance with guidelines. Acute nausea and vomiting were well controlled, but high incidences of delayed nausea occurred in both HEC and MEC patients. Delayed vomiting (p < 0.0001) was significantly less frequent in patients receiving three compared with 2 antiemetics. Female sex was a major risk factor for CINV. Medical staff tended to overestimate the incidence of CINV. Among HEC regimens, the incidence of CINV and the degree of nausea on day 1 of anthracycline-cyclophosphamide combination therapy were higher than with a cisplatin-based regimen. Adherence to antiemetic guidelines effectively controls vomiting but is less effective against delayed nausea in HEC and MEC patients. Identification of individual risk factors, such as female sex, will assist in the development of personalized treatments for CINV. More intensive antiemetic therapy or a different modality of prophylaxis should be considered for the control of acute CINV in an anthracycline-cyclophosphamide regimen.

Difference in the emetic control among highly emetogenic chemotherapy regimens: Implementation for appropriate use of aprepitant

Although antiemetic medication based on the emetogenicity of the cancer chemotherapy regimen is recommended, emetic control varies even among highly emetogenic chemotherapy (HEC). In the present study, we retrospectively investigated the rates of emetic control by a combination of granisetron, 5-HT3 antagonist and dexamethasone in various HEC regimens, including 5 single-day chemotherapy regimens such as gemcitabine/cisplatin (GEM/CDDP), epirubicin/cyclophosphamide (EPI/CPA), pemetrexed or vinorelbine/cisplatin (PEM or VNR/CDDP), doxorubicin/bleomycin/vinblastine/dacarbazine (ABVd) and rituximab/doxorubicin/cyclophosphamide/vincristine/prendisolone (R-CHOP21), and 2 multiple-day chemotherapy regimens such as 5-fluorouracil/cisplatin (5-FU/CDDP) and bleomycin/etoposide/cisplatin (BEP). Complete response (no emesis, no rescue treatment) during the overall period (days 1-5) was assessed as the primary endpoint. Chemotherapy-induced nausea and vomiting was well-controlled (complete response >70%) in GEM/CDDP and R-CHOP21, but not in other regimens. The effect of a triple antiemetic medication including aprepitant (APR) was subsequently examined in patients receiving EPI/CPA and 5-FU/CDDP. Complete response was significantly improved in patients receiving 5-FU/CDDP but not in those receiving EPI/CPA, although the complete protection from vomiting significantly increased in both cases. Of note, the administration of APR for 5 days, but not for 3 days, was required to completely block the incidence of vomiting during the 7 days of the observation period in patients receiving 5-FU/CDDP. These findings suggest that APR should be used appropriately based on the emetogenicity of HEC regimens.

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

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 prospective observational study of patients receiving the first cycle of HEC regimens with CDDP and without CDDP or MEC was performed. Eligible patients completed a 6-day diary recording emetic episodes, nausea assessment, and antiemetic medication use. Physicians and nurses estimated the incidence of acute and delayed CINV after the first administration of HEC and MEC. The observed incidence rates of CINV were compared with the rates predicted by healthcare providers. Aprepitant was given to patients receiving HEC regimes with CDDP. Twenty-nine physicians and nurses and 95 patients (87% receiving HEC and 14% MEC) were recruited. The global control of CINV was 66.67% for all patients and 73.33%, 47.06%, and 55.56% for patients receiving HEC regimens with CDDP, HEC regimens without CDDP and MEC, respectively. Physicians and nurses underestimated the control of acute CINV in patients receiving HEC regimens with CDDP, but they accurately predicted the control of delayed CINV. All physicians and nurses predicted the control of acute CINV after HEC regiments without CDDP and after MEC quite accurately, whereas they overestimated the control of delayed CINV after both regimens. Aprepitant allows for better control of CINV in HEC regimens with CDDP, and this control is accurately perceived by physicians and nurses. However, physicians and nurses overestimate the control of delayed CINV after HEC regimens without CDDP and after MEC. CINV is still an important target for improved therapeutic intervention and the healthcare providers must be aware of its actual incidence.

Phase III results for the novel neurokinin-1 (NK-1) receptor antagonist, casopitant: Single oral dosing regimen for chemotherapy-induced nausea and vomiting (CINV) in patients (Pts) receiving highly emetogenic chemotherapy (HEC)

9549 Background: In a phase II dose-ranging trial, casopitant, a novel NK-1 receptor antagonist, demonstrated efficacy in preventing CINV in pts receiving HEC. This Phase III trial evaluated 2 casopitant dosing regimens, here we present results of a single oral dose of casopitant (150 mg) added to ondansetron/dexamethasone (OND/DEX) for the prevention CINV events in pts receiving HEC. Methods: This multinational, double-blind, active-controlled trial included 810 pts, with 99% receiving cisplatin-based HEC regimens for up to 6 cycles. Pts were randomized to receive no additional therapy (CTRL; OND 32 mg IV + DEX 20 mg PO), or a single dose casopitant arm (150 mg PO + OND 32 mg IV + DEX 12 mg PO) D1, plus DEX 8 mg PO BID D2–4 for all pts. An additional arm evaluated a 3-day IV/oral dose (casopitant 90 mg IV + OND 32 mg IV + DEX 12 mg PO) on D1 plus casopitant 50 mg PO D2–3 + DEX 8 mg PO QD D2–4. Complete Response (CR; no vomiting/retching, rescue medications) in the first 120 hours of HEC was the primary endpoint. Results: In the first 5 days of cycle 1, pts receiving a single oral dose of casopitant achieved a statistically significant improvement (2.5% level of significance adjusted for 2 primary comparisons) in CR rates compared with CTRL. This clinical benefit appeared to be maintained in cycles 2–6 of HEC. Significant improvements were observed in CR in the acute and delayed phases. Clinically meaningful improvements in the secondary endpoints of no significant nausea (SN), and no nausea were also observed. AEs occurred with similar frequency in all arms. Common AEs were neutropenia, leukopenia and anemia. Conclusions: A single oral dose of casopitant added to a regimen of OND/DEX provided a clinically significant reduction in the number of pts experiencing CINV events over the first 5 days after HEC. This benefit appeared to be maintained through repeat cycles. This regimen was generally well tolerated over all cycles. Cycle of HEC Endpoints (0–120 hrs) CTRL n=265 (%) 150 mg PO D1 n=266 (%) P-value 1 Complete Response 175 (66) 228 (86) <0.0001 Acute (0–24 hrs) 234 (88) 253 (95) 0.0044 Delayed (24–120 hrs) 175 (66) 228 (86) <0.0001 No vomiting 179 (68) 236 (89) <0.0001 No SN (VAS < 25 mm) 184 (69) 207 (78) 0.0272 No nausea (VAS <5 mm) 121 (46) 151 (57) 0.0105 2 Complete Response 113/146 (77) 123/131 (94) NA 3 Complete Response 92/118 (78) 89/97 (92) NA 4 Complete Response 66/89 (74) 70/75 (93) NA 5 Complete Response 13/15 (97) 10/11 (91) NA 6 Complete Response 5/9 (56) 9/9 (100) NA Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline

1225 Ondansetron (OND) vs granisetron (GRA) in the control of chemotherapy-induced acute emesis

Nausea and Vomiting (N/V) are very frequent side effects of cancer chemotherapy. 5HT3 receptors antagonists are new antiemetic drugs that can improve quality of life of cancer patients receiving chemotherapy. We have conducted a multicentric randomized study to compare the efficacy and tolerability of two 5HT3 receptors antagonist: OND and GRA. We enrolled 118 non-pretreated cancer pts (70 females, 48 males) to receive OND 0.15 mg/kg iv dl (repeated at 2 and 4 hrs) (116 cycles) or GRA 40 mcr/kg iv dl (117 cycles) before chemotherapy regimen. Each pt was randomized to receive one of two schedules at first cycle and the other schedule at second cycle. The main patient characteristics were: mean age 51 yrs, KI 0–3.48 (41%) pts received highly emetogenic chemotherapy (HE), 70 (59%) pts received moderate emetogenic chemotherapy (ME). Thirty-six per cent of pts had breast cancer, 24% lung, 16% LH/LNH, 24% other. Of the total 233 cycles administered (93 HE, 140ME) we have registered the following results: (1) HE regimen: N/V grade (G)1 11% (OND) and 11% (GRA), G2 17% (OND) and 17% (GRA), G3 4% (OND) and 2% (GRA). Seventeen per cent (OND) and 20% (GRA) had not N/Y. (2) ME regimen: N/V grade (G) 1 16% (OND) and 16% (GRA), G2 15% (OND) and 11% (GRA), G3 2% (OND) and 3% (GRA). Seventeen per cent (OND) and 21% (GRA) had not N/V. The main toxicities were: headache 24% (OND) and 23% (GRA), light-headedness 13% (OND) and 18% (GRA), constipation 11% (OND) and 6% (GRA), other 6% (OND) and 6% (GRA). None of these differences were statistically significant. It is to note that each pt was requested to express a preference between the two drugs: 22% of pts chose OND, 38% GRA and 40% expressed no preference. These differences are statistically significant (α = 0.05). In conclusion we think that OND and GRA are effective but the two drugs are equally active and toxic. From a subjective point of view we noted a trend in favour of GRA.