Control Of Chemotherapy-induced Nausea And Vomiting In Patients Research Articles

Outcomes of chemotherapy-induced nausea and vomiting guideline adherence in pediatric and adult patients: a systematic review.

This study describes chemotherapy-induced nausea and vomiting (CINV) control rates in pediatric and adult patients who did or did not receive guideline-consistent CINV prophylaxis. We conducted a systematic literature review of studies published in 2000 or later that evaluated CINV control in patients receiving guideline-consistent vs. guideline-inconsistent CINV prophylaxis and reported at least one CINV-related patient outcome. Studies were excluded if the guideline evaluated was not publicly available or not developed by a professional organization. Over-prophylaxis was defined as antiemetic use recommended for a higher level of chemotherapy emetogenicity than a patient was receiving. We identified 7060 citations and retrieved 141 publications for full-text evaluation. Of these, 21 publications (14 prospective and seven retrospective studies) evaluating guidelines developed by six organizations were included. The terms used to describe CINV endpoints and definition of guideline-consistent CINV prophylaxis varied among studies. Included studies either did not address over-prophylaxis in their definition of guideline-consistent CINV prophylaxis (48%; 10/21) or defined it as guideline-inconsistent (38%; 8/21) or guideline-consistent (3/21; 14%). Eleven included studies (52%; 11/21) reported a clinically meaningful improvement in at least one CINV endpoint in patients receiving guideline-consistent CINV prophylaxis. Ten reported a statistically significant improvement. This evidence supports the use of guideline-consistent prophylaxis to optimize CINV control. Institutions caring for patients with cancer should systematically adapt CINV CPGs for local implementation and routinely evaluate CINV outcomes.

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.

English

BACKGROUND Chemotherapy-induced nausea and vomiting (CINV) is a frequent and feared adverse effect of cancer chemotherapy. International guidelines recommend combinations of 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, dexamethasone, and/or neurokinin-1 (NK1) receptor antagonists for the control of CINV in patients receiving highly emetogenic chemotherapy (HEC) as a part of their treatment. Even though, nausea in delayed period is less controlled and poses a major concern for these patients. METHODS This open label, prospective study was conducted in a rural medical college in Etawah District in Uttar Pradesh, India from November 2017 to November 2018 over a period of 1 year to observe the efficacy of low dose (5 mg OD) olanzapine in combination with standard anti-emetic regimen for the prevention of CINV. Olanzapine is a food and drug administration (FDA) approved antipsychotic drug that has anti-emetic activity and has shown to improve CINV. Low dose olanzapine along with a standard combination of ondansetron, dexamethasone and aprepitant was given to patients receiving highly emetogenic chemotherapy (Cisplatin >70 mg/m2 or doxorubicin-cyclophosphamide combination). CINV was assessed using common toxicity criteria of adverse events (CTCAE) version 5.0. RESULTS Complete response to nausea was observed in 90.90 %, 60.60 % and 54.54 % in acute, delayed and overall period respectively. Complete response to vomiting was observed in 96.96 %, 69.69 % and 66.66 % in acute, delayed and overall period respectively. Complete response to Grade-2 (or above) nausea was observed in 96.96 %, 93.93 % and 90.90 % in acute, delayed and overall period, respectively. Daytime Grade -3 somnolence which was seen in 2/33 patients (6.06 %) was attributable to olanzapine. Patients receiving olanzapine were more likely to have complete response of nausea and emesis in the early, late, and overall assessment periods especially of higher grade (G2 and G3). CONCLUSIONS The authors concluded that low dose olanzapine 5 mg OD combined with an NK1- receptor antagonist, a 5-HT3–receptor antagonist, and dexamethasone is safe and efficacious in the prevention of CINV in patients receiving HEC. KEYWORDS Olanzapine, Low Dose, CINV, HEC

Evaluating the incidence of chemotherapy-induced nausea and vomiting in patients with B-cell lymphoma receiving dose-adjusted EPOCH and rituximab.

Studies evaluating antiemetic prophylaxis have primarily focused on the solid tumor setting and single-day regimens. This study evaluates antiemetic prophylaxis and chemotherapy induced nausea and vomiting (CINV) in patients with lymphoma receiving a multiday doxorubicin-cyclophosphamide containing regimen. This was a retrospective, single center, cohort study evaluating patients with aggressive non-Hodgkin B-cell lymphoma receiving dose-adjusted R-EPOCH in the hospital. Data was collected from the electronic medical record from April 2016 to September 2019. Complete response over 120 hours was the primary outcome. Secondary outcomes included complete response during the acute and delayed phases as well as complete control. A total of 73 patients who received dose adjusted R-EPOCH were identified. Most patients (n = 39, 53%) were male with a the median age was 63 years (range: 21-81). Most patients received ondansetron 16 mg once daily (n = 48, 66%) on days 1-5 as antiemetic prophylaxis with a minority receiving either dexamethasone (n = 8) or an NK1 antagonist (n = 13) in addition to ondansetron. Complete response rate was 32% and the complete response in the acute and delayed phase was also 32%. Control of CINV in patients with lymphoma hospitalized to receive dose-adjusted R-EPOCH was suboptimal, with only 32% of patients achieving complete response. Nearly three-quarters of patients received only a 5HT3 receptor antagonist as scheduled antiemetic therapy without an NK1 receptor antagonist. This data supports the importance of improving awareness of regarding multiday CINV guidelines and ensuring timely update and implementation of these evidence-based guidelines.

Olanzapine-containing antiemetic therapy for the prevention of carboplatin-induced nausea and vomiting

There remains an unmet clinical need for the control of chemotherapy-induced nausea and vomiting (CINV), particularly in the prevention of nausea and the delayed phase control. We evaluated the efficacy and safety of antiemetic therapy with olanzapine, a neurokinin-1 receptor antagonist, a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist and dexamethasone in patients receiving carboplatin-containing chemotherapy. Olanzapine inhibits signalling via multiple neurotransmitter receptors involved in CINV. Chemotherapy-naïve patients with lung cancer who received carboplatin-containing chemotherapy were enrolled in this phase-II study. Patients received olanzapine, aprepitant, a 5-HT3 receptor antagonist and dexamethasone. The primary endpoint was the complete response rate (no vomiting and no rescue therapy) during 120h after administration of chemotherapy agents. Thirty-three patients received olanzapine-containing antiemetic therapy. The overall complete response rate was 93.3% (95% confidence interval, 80.4-98.3%). The frequency of nausea was 15.2% in the delayed phase and 18.2% in the overall phase. Somnolence was observed in 16 patients. Adding olanzapine to antiemetic therapy with aprepitant, a 5-HT3 receptor antagonist and dexamethasone improved CINV control in patients receiving carboplatin-containing chemotherapy.

Antiemetic efficacy and safety of granisetron or palonosetron alone and in combination with a corticosteroid for ABVD therapy-induced nausea and vomiting

BackgroundAntiemetic effects and safety of granisetron or palonosetron alone and in combination with a corticosteroid against chemotherapy-induced nausea and vomiting (CINV) were retrospectively evaluated in patients with Hodgkin lymphoma receiving adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) therapy.MethodsA total of 39 patients were eligible for this study. Before ABVD therapy, granisetron or palonosetron was intravenously administered with or without a corticosteroid (dexamethasone or hydrocortisone) and aprepitant. The proportions of patients with complete control (CC) during the overall (0–120 h after the start of ABVD therapy), acute (0–24 h) and delayed (24–120 h) phases were evaluated. CC was defined as no vomiting and no use of antiemetic rescue medication with only grade 0–1 nausea.ResultsGranisetron and palonosetron were administered in 21 and 18 patients, respectively. The CC rate during the acute, delayed and overall phases was not statistically different between the two groups. The CINV was completely controlled during overall phase in 58.3% of patients receiving granisetron or palonosetron in combination with a corticosteroid, whereas in 11.1% of those without co-treatment of a corticosteroid (P < 0.05). There were significantly higher frequencies of anorexia, leucopenia and neutropenia in the palonosetron group. There is a statistically significant difference in the frequency of febrile neutropenia between presence and absence of a corticosteroid (p = 0.024).ConclusionThese findings suggested that a combination use of a corticosteroid with a 5-HT3 receptor antagonist was preferable for CINV control in patients with Hodgkin lymphoma receiving ABVD therapy, although the careful management of febrile neutropenia is required.Trial registrationThe study approval numbers in the institution; 24–12 and 24–359. Registered April 17, 2012 and June 21, 2012.

Genetic risk factors for chemotherapy-induced nausea and vomiting in patients with cancer receiving cisplatin-based chemotherapy.

Younger age and female sex have already been well-known risk factors for chemotherapy-induced nausea and vomiting (CINV), and 30-50% of cancer patients still suffer from CINV. Genetic polymorphisms are suggested to influence antiemetic treatment response. This study included a subset of patients previously enrolled in a randomised controlled trial; 156 patients were evaluated. This study aimed to evaluate the role of pharmacogenomic polymorphisms relevant to antiemetic response in patients with cancer receiving cisplatin-based chemotherapy. The study's efficacy endpoint was the proportion of patients with complete response (CR). The study endpoint was evaluated separately in the acute (CR0-24) and delayed (CR24-120) phases. Thirteen polymorphisms were genotyped, and the association of these genotypes with the efficacy of prophylactic antiemetics was then investigated. Confounding variables for the CR were identified using stepwise multivariate logistic regression analysis. Age and sex were included as independent variables by the forced-entry method, and the stepwise method was used to select the pharmacogenomic factors for inclusion as independent variables. Multivariate logistic regression analysis revealed that the ERCC1 8092AA (odds ratio [OR] = 11.25; 95% confidence interval [CI] 1.74-72.71; p = 0.011) and female sex (OR = 3.63; 95% CI 1.14-11.58; p = 0.029) were significant predictors of CR0-24. No significant association of CR24-120 with pharmacogenomic polymorphisms was found via multivariate logistic regression analysis. ERCC1 polymorphism influenced the extent of CINV control in patients receiving cisplatin-based chemotherapy. Clinical trial information: UMIN 000009335.

Comprehensive study of risk factors for chemotherapy-induced nausea and vomiting in cancer patients receiving cisplatin-based chemotherapy: A TRIPLE pharmacogenomics study.

10091 Background: Chemotherapy-induced nausea and vomiting (CINV) is one of the most unpleasant adverse effects of chemotherapy. Resistance to prophylactic antiemetic treatment is problematic, with 30%–50% of patients experiencing unsatisfactory control. Younger age and female sex are well-known risk factors for CINV. Genetic polymorphisms are suggested to influence antiemetic treatment response. Methods: This study included a subset of patients previously enrolled in a randomised controlled trial. This study aimed to evaluate the role of pharmacogenomic polymorphisms relevant to antiemetic response in patients with cancer receiving cisplatin-based chemotherapy. The study’s efficacy endpoint was the proportion of patients with complete response (CR). The study endpoint was evaluated separately in the acute (CR0-24) and delayed (CR24-120) phases. Thirteen polymorphisms were genotyped, and the association of these genotypes with the efficacy of prophylactic antiemetics was then investigated. Confounding variables for CR were identified using stepwise multivariate logistic regression analysis. Age and sex were included as independent variables by the forced-entry method, and the stepwise method was used to select the pharmacogenomic factors for inclusion as independent variables. Results: In this genetic polymorphism association study, 156 patients with solid cancer were evaluated. Multivariate logistic regression analysis revealed that ERCC1 8092AA (odd ratio [OR]: 11.251; 95% confidence interval [CI]: 1.741–72.712, P = 0.011) and female sex (OR = 3.630; 95% CI = 1.138–11.578, P = 0.029) were significant predictors of CR0-24. No significant association of CR24-120 with pharmacogenomic polymorphisms was found via multivariate logistic regression analysis. Conclusions: ERCC1 polymorphism might be influenced the extent of CINV control in patients receiving cisplatin-based chemotherapy. Clinical trial information: 000009335.

Phase III study of NEPA, a fixed combination of netupitant and palonosetron, versus an aprepitant regimen for prevention of chemotherapy-induced nausea and vomiting (CINV).

10090 Background: Co-administration of multiple antiemetics that inhibit several molecular pathways involved in emesis is required to optimize CINV control in patients receiving highly emetogenic chemotherapy (HEC). NEPA, a novel fixed combination of a highly selective NK1 receptor antagonist (RA), netupitant (300 mg), and palonosetron (PALO 0.50 mg), a pharmacologically distinct 5-HT3RA, has shown superior CINV prevention compared to PALO in cisplatin and AC-based settings. This study is the first head-to-head comparison of NEPA versus an aprepitant (APR)/granisetron (GRAN) regimen, with the primary objective being to demonstrate non-inferiority in preventing CINV. Methods: This randomized, double-blind, parallel group Phase III study conducted in an Asian population was designed to compare efficacy and safety of a single oral dose of NEPA with a 3-day oral APR/GRAN regimen in chemotherapy-naïve patients receiving cisplatin-based HEC. All patients also received oral dexamethasone (DEX) on days 1-4. The primary efficacy endpoint was complete response (CR: no emesis, no rescue medication) during the overall (0-120 h) phase. Non-inferiority was defined as a lower 95% CI greater than the non-inferiority margin set at -10%. Secondary efficacy endpoints included no emesis and no significant nausea (NSN: &lt; 25mm on 100mm VAS). Results: Treatment groups were comparable for the 828 patients analyzed: predominantly male (71%); mean age 54.5 years; ECOG 0-1 (98%); lung cancer (58%). NEPA demonstrated non-inferiority to APR/GRAN for overall CR; no emesis and NSN rates favored NEPA. Most frequent study drug-related adverse events (AEs) for NEPA included constipation (8.0%) and hiccups (2.7%). The type/incidence/severity of AEs were similar for NEPA and APR/GRAN. Conclusions: In this first study comparing NK1RA regimens and 4 days of DEX, NEPA administered only on day 1 was non-inferior to a 3-day oral APR/GRAN regimen in preventing CINV associated with HEC. [Table: see text]

Safety, efficacy, and patient acceptability of single-dose fosaprepitant regimen for the prevention of chemotherapy-induced nausea and vomiting

Control of chemotherapy-induced nausea and vomiting (CINV) is a crucial factor in ensuring that patients undergoing cancer chemotherapy can get the full benefit of therapy. Current antiemetic guidelines recommend that the neurokinin-1 receptor (NK-1R) antagonist aprepitant should be used as part of a combination regimen with dexamethasone and a serotonin receptor antagonist for the prevention of CINV in patients receiving highly emetogenic chemotherapy (HEC). Fosaprepitant is a water-soluble N-phosphoryl derivative of aprepitant that, when infused, is rapidly metabolized back to an active aprepitant. The existing literature in PubMed about fosaprepitant was screened and selected in order to address the emerging data from two randomized clinical trials evaluating the efficacy and safety of a single-dose fosaprepitant regimen. These phase III trials demonstrated that fosaprepitant given as a single intravenous dose of 150 mg was either noninferior to the conventional 3-day aprepitant or significantly superior to placebo for the prevention of acute and delayed CINV in patients receiving high-dose cisplatin. In both trials, fosaprepitant was well tolerated although more frequent infusion-site adverse events were observed with fosaprepitant. The new dosage regimen of fosaprepitant, therefore, would be an option for CINV control in patients receiving cisplatin-based chemotherapy. The clinical efficacy is consistent with the findings from a time-on-target, positron-emission tomography study evaluating the NK-1R occupancy in the central nervous system (CNS) over 5 days after a single-dose infusion of 150 mg fosaprepitant in healthy participants. The single-dose regimen is capable of blocking more than 90% of the NK-1Rs in the CNS for at least 48 hours after infusion, which is sufficient to control delayed CINV for 2 to 5 days after HEC. The new dosage regimen of fosaprepitant can provide a simplified treatment option that maintains high protection while ensuring adherence to scheduled antiemetic medication throughout most of the 5-day period encompassing the major risk for CINV.

Palonosetron: A Second-Generation 5-Hydroxytryptamine Receptor Antagonist

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles and patient risk factors (female gender, younger age, alcohol consumption, history of motion sickness) are the major risk factors for CINV. The use of 5-hydroxytryptamine (5-HT)3 receptor antagonists plus dexamethasone has significantly improved the control of acute CINV, but delayed nausea and vomiting remains a clinical problem. A new agent, palonosetron, has recently been approved for the prevention of acute CINV in patients receiving either moderately or highly emetogenic chemotherapy and for the prevention of delayed CINV in patients receiving moderately emetogenic chemotherapy. Palonosetron is a 5-HT3 receptor antagonist with a longer half-life and a higher binding affinity than first-generation 5-HT3 receptor antagonists. In a single dosing study, palonosetron was highly effective in controlling CINV compared with a single dose of dolasetron or ondansetron in patients receiving moderately emetogenic chemotherapy. Palonosetron in combination with dexamethasone demonstrated control of CINV in patients receiving highly emetogenic chemotherapy. Palonosetron appeared to be as effective in subsequent courses of chemotherapy compared with the initial course of chemotherapy. There were no clinically relevant differences seen among palonosetron, ondansetron or dolasetron in laboratory, electrocardiographic or vital-sign changes, and adverse reactions reported in the clinical trials were the most common reactions reported for the 5-HT3 receptor antagonist class. Recent studies using palonosetron-based anti-emetic combinations in moderately and highly emetogenic chemotherapy, as well as in the clinical setting of multiple-day chemotherapy, have been reported. Future studies may consider the use of palonosetron with current and other new agents and in other clinical settings, such as bone marrow transplantation and radiation therapy.

Relative efficacy of various 5- hydroxytryptamine receptor antagonists in the prevention and control of acute nausea and vomiting associated with platinum-based chemotherapy

8623 Background: The introduction of 5-Hydroxytryptamine-3 receptor (5-HT3) antagonists has represented a significant clinical advance in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV), particularly for patients receiving highly emetogenic platinum-based regimens. However no study to date has compared the relative efficacy of Dolasetron, Granisetron, Ondansetron and Palonosetron with Dexamethasone in the prevention and control of acute CINV in patients undergoing platinum-based therapy. Methods: Retrospective data were reviewed for 207 consecutive patients receiving Platinum-based chemotherapy in our infusion center between November 1999 and August 2005. Patients receiving 5-HT3 antagonists without Dexamethasone (n=11) were not eligible for the study. Further 15 patients were excluded because of no documentation of CINV. The remaining 181 patients constitute the subject of this study. Patient characteristics including age, sex, race, diagnosis, history of heavy alcohol intake, chemotherapy regimen administered, number of cycles, and performance status at the start of therapy were noted. Primary outcome measure was complete control of acute CINV. National Cancer Institute Common Toxicity Criteria version 2.0 was used to assess toxicity. Results: The 181 patients received 572 cycles of platinum-based therapy. Dolasetron (n=157), Granisetron (n=81), Ondansetron (n=131) and Palonosetron (n=203) (each given with Dexamethasone) achieved complete control of vomiting in 89.8%, 95.5%, 92.3% and 88.1% (ρ=0.86) of cycles respectively. Respectively, complete nausea control was observed in 68.1%, 75.3%, 69.4% and 73.3% (ρ=0.35). DEX 20 mg was not superior to 10mg in complete control of nausea and vomiting (ρ=0.06 and ρ=0.67 respectively). Similarly complete control of nausea and vomiting (ρ=0.12 and ρ=0.10 respectively) was not significantly different in patients getting cisplatin compared to carboplatin based regimens. Conclusion: This study does not demonstrate a significant difference in the efficacy of the four 5-HT3 antagonists in controlling acute CINV. The higher dose of Dexamethasone confers no added benefit over the lower 10mg dose. No significant financial relationships to disclose.