An Update in Our Understanding of the Relationships Between Gene Polymorphisms and Chemotherapy-Induced Nausea and Vomiting.
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ABSTRACT:
SUBMITTER: Jin Y
PROVIDER: S-EPMC8458022 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Despite current advances in antiemetic treatments, between 30% to and 60% of oncology patients experience chemotherapy-induced nausea (CIN) and 13% to 33% report chemotherapy-induced vomiting (CIV). Inter-individual differences are observed in the occurrence and severity of chemotherapy-induced nausea and vomiting (CINV). This review summarizes and critiques studies on associations between occurrence and severity of CINV and polymorphisms in serotonin receptor, drug metabolism, and drug transport pathway genes. Sixteen studies evaluated the associations between the occurrence and/or severity of CINV and single nucleotide polymorphisms (SNPs). Across these studies, three SNPs in 5-hydroxytryptamine receptor (5-HT3R) genes, two alleles of the cytochrome P450 family 2 subfamily D member 6 (CYP2D6) gene, and three SNPs in ATP binding cassette subfamily B member 1 (ABCB1) gene were associated with the occurrence and severity of CINV. Given the limited number of polymorphisms evaluated, additional research is warranted to identify new mechanisms to develop more targeted therapies.
| S-EPMC5777158 | biostudies-literature
Project description:ObjectiveTo investigate the correlation between aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphisms and chemotherapy-induced nausea and vomiting (CINV).MethodsA total of 90 Chinese patients with malignant tumors receiving chemotherapy for the first time were recruited in this study. The occurrence of CINV was observed within 120 h after treatment with docetaxel and cis-platinum chemotherapy (DP regimen). The data of the patients (including age, gender, tumor stage, habitual alcohol consumption, motion sickness, morning sickness, and average sleep time prior to chemotherapy) were collected through a questionnaire. ALDH2 rs671 polymorphisms of the patients were analyzed using a multiple single nucleotide polymorphism genotyping, and the Hardy-Weinberg equation was used for genetic linkage analysis. The correlations between the factors including ALDH2 rs671 polymorphisms and the occurrence of CINV were analyzed.ResultsThe incidence of CINV was 48.9% among the patients receiving their first chemotherapy with DP regimen. Univariate analysis indicated that the genetic polymorphisms of ALDH2 rs671 were significantly correlated with the occurrence of CINV (P < 0.05). Multivariate logistic analysis indicated that ALDH2 rs671 mutation (OR: 3.019, 95% CI: 1.056-8.628, P < 0.05) and average sleep time prior to chemotherapy no longer than 6 h (OR: 2.807, 95% CI: 1.033-7.628, P < 0.05) were risk factors for CINV in patients with malignant tumors receiving the first chemotherapy with DP regimen.ConclusionALDH2 gene mutation at rs671 is a risk factor contributing to the occurrence of CINV, and understanding of the underlying mechanism may help to more effectively control the occurrence of CINV.
| S-EPMC10339303 | biostudies-literature
Project description:BackgroundGenotype frequencies for chemotherapy-induced nausea and vomiting (CINV)-related polymorphisms have not yet been reported for Japanese subjects.MethodsWe analyzed 10 genotype frequencies for following polymorphisms associated with the development of CINV: serotonin 5-HT3 receptors (HTR3); neurokinin-1 receptors (Tachykinin-1 receptors, TACR1); dopamine D2 receptors (DRD2); and catechol-O-methyltransferase (COMT).ResultsAll polymorphisms were successfully genotyped in 200 Japanese subjects and were in Hardy-Weinberg equilibrium. Almost all genotype frequencies were similar to those in the HapMap database or in the previous reports, while frequencies for the Y192H polymorphism in TACR1 were different in Japanese subjects from those in a previous report.ConclusionsThe present study revealed genotype frequencies for polymorphisms, which were related to the appearance of CINV in Japanese subjects. Individual therapy based on genotype variations for each race is needed to allow cancer patients to undergo chemotherapy more safely and to understand etiology of CINV.
| S-EPMC4955237 | biostudies-literature
Project description:ObjectiveNausea and vomiting remain life-threatening obstacles to successful treatment of chronic diseases, despite a cadre of available antiemetic medications. Our inability to effectively control chemotherapy-induced nausea and vomiting (CINV) highlights the need to anatomically, molecularly, and functionally characterize novel neural substrates that block CINV.MethodsBehavioral pharmacology assays of nausea and emesis in 3 different mammalian species were combined with histological and unbiased transcriptomic analyses to investigate the beneficial effects of glucose-dependent insulinotropic polypeptide receptor (GIPR) agonism on CINV.ResultsSingle-nuclei transcriptomics and histological approaches in rats revealed a topographical, molecularly distinct, GABA-ergic neuronal population in the dorsal vagal complex (DVC) that is modulated by chemotherapy but rescued by GIPR agonism. Activation of DVCGIPR neurons substantially decreased behaviors indicative of malaise in cisplatin-treated rats. Strikingly, GIPR agonism blocks cisplatin-induced emesis in both ferrets and shrews.ConclusionOur multispecies study defines a peptidergic system that represents a novel therapeutic target for the management of CINV, and potentially other drivers of nausea/emesis.
| S-EPMC10326744 | biostudies-literature
Project description:Netupitant/palonosetron (NEPA; Akynzeo®), available in oral and intravenous (IV) formulations, is a fixed-dose combination of the neurokinin 1 (NK1) receptor antagonist netupitant (or the prodrug, fosnetupitant, in the IV formulation) and the second-generation serotonin 3 (5-HT3) receptor antagonist palonosetron. Administered as a single dose, (fos)netupitant/palonosetron (in combination with dexamethasone) is indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) in adults. In clinical trials, (fos)netupitant/palonosetron plus dexamethasone was associated with high complete response rates (no emesis and no rescue medication) in the acute, delayed and overall phases in patients receiving highly or moderately emetogenic chemotherapy, with efficacy maintained over multiple cycles. Further, oral netupitant/palonosetron was found to be superior to palonosetron and non-inferior to aprepitant plus granisetron in preventing CINV in individual trials. Both the oral and IV formulations of the drug combination are well tolerated. The fixed-dose combination is concordant with guideline recommendations and provides a simple and convenient option for prophylaxis against acute and delayed CINV in patients receiving highly or moderately emetogenic chemotherapy.
| S-EPMC8463343 | biostudies-literature
Project description:BackgroundWe examined the efficacy of olanzapine for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy.MethodsIn a randomized, double-blind, phase 3 trial, we compared olanzapine with placebo, in combination with dexamethasone, aprepitant or fosaprepitant, and a 5-hydroxytryptamine type 3-receptor antagonist, in patients with no previous chemotherapy who were receiving cisplatin (≥70 mg per square meter of body-surface area) or cyclophosphamide-doxorubicin. The doses of the three concomitant drugs administered before and after chemotherapy were similar in the two groups. The two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. Nausea prevention was the primary end point; a complete response (no emesis and no use of rescue medication) was a secondary end point.ResultsIn the analysis, we included 380 patients who could be evaluated (192 assigned to olanzapine, and 188 to placebo). The proportion of patients with no chemotherapy-induced nausea was significantly greater with olanzapine than with placebo in the first 24 hours after chemotherapy (74% vs. 45%, P=0.002), the period from 25 to 120 hours after chemotherapy (42% vs. 25%, P=0.002), and the overall 120-hour period (37% vs. 22%, P=0.002). The complete-response rate was also significantly increased with olanzapine during the three periods: 86% versus 65% (P<0.001), 67% versus 52% (P=0.007), and 64% versus 41% (P<0.001), respectively. Although there were no grade 5 toxic effects, some patients receiving olanzapine had increased sedation (severe in 5%) on day 2.ConclusionsOlanzapine, as compared with placebo, significantly improved nausea prevention, as well as the complete-response rate, among previously untreated patients who were receiving highly emetogenic chemotherapy. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02116530.).
| S-EPMC5344450 | biostudies-literature
Project description:Chemotherapy-induced nausea and vomiting (CINV) is one of the most common symptoms feared by patients, but may be prevented or lessened with appropriate medications. Several antiemetic options exist to manage CINV. Corticosteroids, serotonin receptor antagonists, and neurokinin receptor antagonists are the classes most commonly used in the prevention of CINV. There are many alternative drug classes utilized for the prevention and management of CINV such as antihistamines, benzodiazepines, anticonvulsants, cannabinoids, and dopamine receptor antagonists. Medications belonging to these classes generally have lower efficacy and are associated with more adverse effects. They are also not as well studied compared to the aforementioned agents. This review will focus on dronabinol, a member of the cannabinoid class, and its role in CINV. Cannabis sativa L. (also known as marijuana) contains naturally occurring delta-9-tetrahydrocannibinol (delta-9-THC). The synthetic version of delta-9-THC is the active ingredient in dronabinol that makes dronabinol an orally active cannabinoid. Evidence for clinical efficacy of dronabinol will be analyzed in this review as monotherapy, in combination with ondansetron, and in combination with prochlorperazine.
| S-EPMC4869612 | biostudies-other
Project description:IntroductionNausea and vomiting are two of the most frequent and troubling side effects patients experience during chemotherapy, interfering with compliance with cancer therapies and quality of life. While newly available treatments have improved our ability to manage nausea and vomiting, anticipatory and delayed nausea and vomiting are still major problems for patients receiving chemotherapy. Many cancer patients consider delaying future chemotherapy cycles and some contemplate stopping chemotherapy altogether because of their fear of experiencing further nausea and vomiting.Areas coveredThe purpose of this article is to provide an overview of the pathopsychophysiology of chemotherapy-induced nausea and vomiting (CINV), the recommended guidelines for treatment, and current agents in late-stage clinical trials, and future research needs to address the continued challenges of treatment-related nausea and vomiting.Expert opinionDespite advances in pharmaceutical and behavioral therapies, and the provision of standard clinical guidelines for effectively managing CINV, patients continue to experience it. Moreover, control of nausea, acute and delayed, and anticipatory nausea and vomiting remains an important, unmet need among cancer patients. It is critical to focus attention on better understanding the mechanisms underlying nausea, anticipatory symptoms and delayed symptoms.
| S-EPMC3938333 | biostudies-literature
Project description:PurposeWe aim to investigate the correlation between gene polymorphisms and cisplatin chemotherapy-induced nausea and vomiting (CINV), which was prevented by olanzapine or aprepitant triple antiemetic regimen.MethodsBefore chemotherapy, the blood samples of 89 malignant tumor patients who received multi-day chemotherapy with cisplatin were collected for sequencing and typing. As there were duplicate patients enrolled in different chemotherapy cycles, there were a total of 190 cases. The patients were divided into two groups randomly, who received the triple antiemetic regimen of olanzapine or aprepitant combined with 5-HT3RA and dexamethasone. The main evaluation indicators were the total protection (TP) rate in the acute phase (0-24 h), the delayed phase (25-120 h) and the overall phase (0-120 h).ResultsUnivariate analysis was performed on genetic loci that reached H-W balance with TP. In the olanzapine group, increased TP in the acute phase was associated with HTR3A rs1176719 non-GG (P < 0.05) genotype etc. Increased TP in the delayed phase was associated with HTR3A rs1176719 non-GG (P < 0.05) genotype etc. In the aprepitant group, increased TP in the acute phase was associated with the MTHFR rs1801131 TT (P < 0.05) genotype etc. Increased TP in the delayed phase was associated with HTR3A rs1062613 CC (P < 0.05) genetype ect. Multivariate Logistic regression analysis showed that HTR3B rs7943062GG (P < 0.05) genotype etc. were correlated with increased TP in the delayed phase. MTHFR rs1801131TT genotype was associated with increased TP in the acute phase (P < 0.05) and delayed phase (P < 0.05).ConclusionThis study found that gene polymorphisms, including HTR3B (rs1062613, rs1176719, rs2276303), HTR3B (rs45460698, rs7943062), HTR3C (rs6766410), ERCC1 (rs3212986), ERCC4 (rs744154) and MTHFR(rs1801131), may be independent prognostic factors for CINV.
| S-EPMC10625179 | biostudies-literature
Project description:PurposeThis study aims to determine the incidence of nausea and vomiting (CINV) after moderately emetogenic chemotherapy (MEC), under medical practice conditions and the accuracy with which physicians perceive CINV.MethodsChemotherapy-naive patients receiving MEC between April 2012 and May 2013 were included. Patients completed a diary of the intensity of nausea and number of vomiting episodes. Complete response and complete protection were assessed as secondary endpoints.ResultsOf 261 patients included, 240 were evaluated. Median age was 64 years, 44.2 % were female and 11.2 % were aged less than 50 years; 95.3 % of patients received a combination of 5-hydroxytryptamine 3 (5-HT3) antagonist + corticosteroid as antiemetic treatment. Vomiting within 5 days of chemotherapy administration occurred in 20.8 %, nausea in 42 % and significant nausea in 23.8 % of patients. An increase in the percentage of patients with significant nausea (from 9.4 to 21.7 %) and vomiting (from 9.2 to 16.5 %) was observed from the acute to the delayed phase. Complete response was 84.2 % in the acute phase, 77 % in the late phase and 68.9 % in overall period. Complete protection was 79.5 % in the acute phase, 68.8 % in the late phase and 62.4 % throughout the study period. Physicians estimated prophylaxis would be effective for 75 % of patients receiving MEC, compared with 54.1 % obtained from patients' diary.ConclusionDespite receiving prophylactic treatment, 31 % of patients did not achieve a complete response and 38 % complete protection. In general, nausea was worse controlled than vomiting. The results also showed the late phase was worse controlled than the acute phase in all variables. Healthcare providers overestimated the effectiveness of antiemetic prophylaxis.
| S-EPMC4519584 | biostudies-literature