Nausea In Cancer Patients Research Articles

Management of psychiatric disorders in patients with cancer.

Management of psychiatric disorders in patients with cancer.

Factors Associated with Chemotherapy Induced Nausea in Cancer Patients: A Case-Control Study

Background: Chemotherapy-induced nausea (CIN) is one of the most common and uncomfortable symptoms in cancer patients, and different factors can be associated with it. Objectives: This study aimed to determine different factors associated with CIN in cancer patients. Methods: A total of 144 cancer patients were selected by convenience sampling. The patients at acute phase of chemotherapy were assigned to case group (n = 58) if they had nausea or to control group (n = 86) if they did not have nausea. The patients' data were collected using a researcher-made questionnaire including items on potential factors for CIN through interviews with the patients and according to their medical records. Logistic regression models were used to conduct data analysis, and the correlations in question were expressed as odds ratio (OR) at 95% confidence interval (CI). Results: The results showed that the chance of nausea increased by 6.4, 2.4, 1.2, and 1.5 times in case of expected nausea, pain, carbohydrate intake, and smelling a specific odor, respectively. The increasing nausea-inducing effect of drugs led to increased chance of post-chemotherapy nausea (OR = 2.366). Conclusions: Having pain, expecting nausea, carbohydrate intake, smelling a certain odor, and high emetogenic potential of chemotherapy are effective in the development of CIN.

High Feasibility and Safety, but Negligible Efficacy of Acupressure for Treating Nausea in Cancer Patients Admitted to the Palliative Care Unit: A Pilot Study.

Management of nausea is an important dimension of palliative care. The first choice for treating nausea is antiemetics, but their efficacy is inadequate. Acupressure intervention for nausea in cancer patients has been studied as a non-pharmacological therapy, and appears to have had some effect. However, such a therapy has not been well reviewed in patients with terminal cancer. The purpose of this study was to clarify the feasibility of acupressure intervention and examine its safety and preliminary efficacy. We recruited cancer patients that fulfilled the eligibility criteria and were admitted to the palliative care unit, from August 2018 to February 2019, in Tohoku University Hospital, Japan. We conducted a longitudinal assessment of acupressure intervention in a single arm. We identified the patient's research accomplishments and evaluated possible fainting due to the vagal reflex and symptom severity. Descriptive statistics were used to calculate the completion rate for the feasibility and Wilcoxon signed-rank tests to compare the average of continuous variables for the safety and efficacy. Twelve patients participated in this study and completed the procedure. Their average age was 70 years (SD = 9.3), and the most common primary cancer sites were the rectum and pancreas. The blood pressure and pulse rate did not drop sharply. Four patients exhibited decreased nausea but there was no statistically significant difference (P = 0.5). We suggested that acupressure has high feasibility and safety, as an intervention for patients with terminal cancer. However, no significant differences were observed regarding its effect on nausea.

Fixed-Dose Netupitant and Palonosetron for Chronic Nausea in Cancer Patients: A Double-Blind, Placebo Run-in Pilot Randomized Clinical Trial

ContextNo clinical trials have examined the effect of netupitant/palonosetron (NEPA) on chronic nausea in patients with cancer. ObjectivesIn this pilot randomized trial, we assessed the efficacy of NEPA and placebo on chronic nausea. MethodsThis double-blind, parallel, randomized trial enrolled patients with cancer and chronic nausea for at least 1 month, intensity ≥4/10 and not on moderately or highly emetogenic systemic therapies. Patients started with a placebo run-in period from days 1 to 5; those without a placebo response proceeded to the double-blinded phase between days 6 to 15 (NEPA: placebo 2:1 ratio). The primary outcome was within-group change in average nausea over the 24 hours on a 0–10 numeric rating scale between day 5 and 15. ResultsAmong the 53 enrolled patients, 46 proceeded to placebo run-in and 33 had blinded treatment (22 NEPA and 11 placebo). We observed a statistically significant within-group improvement in nausea numeric rating scale between day 5 and 15 in the NEPA group (mean change, −2.0; 95% CI, −3.1 to −0.8) and the placebo group (mean change, −2.3; 95% CI, −3.9 to −0.7). A complete response was achieved in 8 (38%) patients in the NEPA group and 2 (20%) in the placebo group by day 15. No grade 3–4 toxicities were attributed to NEPA. There were no statistically significant between-group differences for the primary/secondary outcomes. ConclusionsNEPA and placebo were associated with similar magnitude of within-group improvement in chronic nausea without significant between-group differences (Clinicaltrials.gov NCT03040726).

Malus domestica reduces chemotherapy-induced nausea and vomiting: A randomized double-blind placebo-controlled clinical trial.

Background:Chemotherapy-induced nausea and vomiting (CINV) is considered as the most common complications of chemotherapy which has a detrimental influence on the quality of life of patients with cancer. We assessed the efficacy of Apple (Malus domestica) syrup for reducing CINV.Materials and Methods:This study was a randomized, double-blind, placebo-controlled trial carried out in a Hematooncology Clinic affiliated to Mazandaran University of Medical Sciences, Sari, Iran (from October 2017 to August 2018). Subjects were randomly allocated to receive apple syrup or placebo along with their previous antiemetic treatment and chemotherapy regimen, three times a day. Thirty-four patients received apple syrup (n = 16) or placebo (n = 18). Statistical analysis was conducted using SPSS software Version 21® (SPSS Inc., Chicago, IL, USA). A P < 0.05 indicated statistical significance.Results:Both acute and delayed nausea grades were significantly lower in M. domestica syrup in comparison to placebo syrup (P = 0.001 and 0.001, respectively). The duration of nausea (P = 0.04) was lower in intervention group compared to placebo group.Conclusion:These findings demonstrated that M. domestica syrup can reduce the severity and duration of nausea in cancer patients who received chemotherapy.

Predictive Factors of Opioid-Induced Nausea in Cancer Patients

Approximately 30% of patients experience nausea after initiation of opioid therapy, which can lead to poor quality of life. We aimed to identify risk factors for opioid-induced nausea at the initiation of opioid therapy by conducting a retrospective review of medical records of patients diagnosed by palliative care specialists with solid cancer and pain at the lesion site at Showa University Hospital between June 2005 and June 2011. The primary endpoint was the development of nausea grade ≥1 according to the Common Terminology Criteria for Adverse Events version 4.0 within 48 hours of initiation of opioid therapy. The median age of the 134 enrolled patients was 67.7 (range 28–95) years. Fifty-three percent were male and 44% had gastrointestinal cancer. Furthermore, 22.4% had opioid-induced nausea. Age (odds ratio (OR) 1.74; 95% confidence interval (CI), 1.13–2.69), edema (OR 5.83; 95% CI, 1.22–28.19), and gastrointestinal cancer (OR 2.61, 95% CI 1.07–6.36) were significantly associated with opioid-induced nausea. Prophylactic antiemetics were found to be ineffective.

The Effects of Peppermint Oil on Nausea, Vomiting and Retching in Cancer Patients Undergoing Chemotherapy: An Open Label Quasi–Randomized Controlled Pilot Study

ObjectivesThe current study evaluated the effects of peppermint oil on the frequency of nausea, vomiting, retching, and the severity of nausea in cancer patients undergoing chemotherapy. DesignA quasi-randomized controlled study. SettingPatients were recruited from the ambulatory chemotherapy unit of a public hospital located (Batman, Turkey) between September 2017 and September 2018. InterventionsThe participants in the intervention group applied one drop the aromatic mixture on the spot between their upper lip and their nose, three times a day for the five days following chemotherapy administration, in addition to the routine antiemetic treatment. Participants in the control group underwent only the routine antiemetic treatment. Main outcome measures VAS-the severity of nausea and the Index of Nausea, Vomiting, and Retching. ResultsThe VAS nausea score was significantly lower after peppermint oil applying in the patients receiving Folfirinox (treatment effect (mean dif.): 4.00±2.28; P<0.001), Paclitaxel-Trastuzumab (treatment effect (mean dif.): 1.70±0.90; P=0.014), Carboplatin-Paclitaxel (treatment effect (mean dif.): 3.71±1.41; P<0.001), and Cyclophosphamide-Adriamycin (treatment effect (mean dif.): 1.41±0.73; P=0.005) excluding cisplatin scedule (treatment effect (mean dif.): 0.56±2,18; P=0.642). We detected a statistical significant difference in the change in frequency of nausea, vomiting, retching in the other all schedules excluding cisplatin schedule (P<0.05). ConclusionsThe peppermint oil was significantly reduced the frequency of nausea, vomiting, retching and the severity of nausea in cancer patients undergoing chemotherapy. Therefore, usage of peppermint oil together with antiemetics after chemotherapy with moderate and low emetic risk may be recommended to cope with CINV.

Complementary and alternative medicines used by cancer patients to cope with nausea

Background: Cancer is a common health problem in the world. Nausea is one of the most common symptoms in cancer patients. Cancer patients often apply to complementary and alternative medicines (CAM) in symptom management.Aim: The aim of this study was to determine the CAM methods used by cancer patients to cope with nausea.Material and Method: The study has a descriptive design and its data were collected in an adult oncology unit of a university hospital between July and September 2019. A total of 205 patients diagnosed with cancer for at least 6 months were included in the study. Data were collected by using the Individual Identification Form and Attitude Scale against Holistic Complementary Medicine. Data were analyzed with SPSS 25.0 package program. Written permission was obtained from the relevant ethics committee, hospital and participants to conduct the study.Results: Sixty and a half percent of the subjects were female and the mean age was 50.64 ± 15.27. While 31.7% of the patients had information about CAM, the main source of information was the internet and social media (64.6%). It was found that 14.63% of the patients applied to a CAM to cope with nausea. The most commonly used method is phytotherapy with 86.67%. The total score environment of the Holistic Complementary Medicine Attitude Scale was 33.49 ± 4.63.Conclusions: It was found that the rate of using CAM in coping with nausea in cancer patients was lower than other symptoms in the literature and the most commonly used method was phytotherapy. Patients' attitudes towards CAM were found to be positive.

CD93-Signaling Regulates Self-Renewal and Proliferation of Chronic Myeloid Leukemia Stem Cells in Mice and Humans and Might be a Promising Target for Treatment

Background: The introduction of BCR/ABL-specific tyrosine kinase inhibitors (TKIs) more than two decades ago revolutionized chronic myelogenous leukemia (CML) therapy. The majority of CML patients treated with TKIs obtain durable cytogenetic and molecular responses. However, only a subgroup of these patients can successfully discontinue TKI therapy and maintain a treatment-free remission (Laneuville et al. 2011). TKI-resistant leukemia stem cells (LSCs) persist in the majority of patients at low levels over a prolonged period. These quiescent, self-renewing LSCs in the BM are the major cause of relapse after drug discontinuation (Holyoake et al, 2017). The selective elimination of LSCs requires the definition of unique signaling pathways that promote self-renewal of LSCs but not of normal HSCs. Based on the documented expression of CD93 on LSCs (Kinstrie et al, 2015), the aim of the present study was to investigate the role of the cell surface receptor CD93 in the regulation of self-renewal of human and murine CML LSCs and its contribution to disease development and progression. Methods and Results: We found CD93 expression on LSCs and leukemia progenitor cells but not on more differentiated leukemia granulocytes in a murine retroviral lineage-negative Sca-1+ c-kit+ (LSK) transduction/transplantation CML model. Next-generation sequencing analysis revealed that Cd93-/- LSCs have a silenced gene expression signature particularly in genes involved in the regulation of gene expression, stem cell maintenance and proliferation. Out of the 1120 genes differentially expressed between BL/6 and Cd93-/- LSCs, 1108 genes were down-regulated. In contrast, naïve BL/6 and Cd93-/- hematopoietic stem cells (HSCs) did not display a dysregulation in these pathways. Functionally, CD93-deficiency in LSCs resulted in impaired self-renewal, reduced LSC frequencies in vitro (at least by a factor of 100, P&amp;lt;0.001) and in the incompetence to induce and propagate CML in mice. To study whether CD93-signaling in LSCs relies on ligand-binding to the extracellular domain of CD93, we generated an extracellular domain deletion mutant of CD93 (mCd93intra). Comparable to transduction with full-length mCd93, the expression of Cd93intra restored colony formation of Cd93-/- LSCs in vitro, suggesting that the maintenance of LSC self-renewal is independent of ligand-binding to the extracellular domain of CD93. Furthermore, analysis of the sub-cellular localization of CD93 in CML cells using a lentiviral expression vector encoding for AcGFP1-N1-Cd93 demonstrated nuclear localization of the CD93 intracellular domain (ICD). SCY1 like pseudokinase 1 (SCYL1), a regulator of gene transcription, directly interacts with the highly charged juxta membrane domain of the cytoplasmic tail of CD93 (Bohlson et al, 2005). Silencing of Scyl1 significantly reduced colony formation of BL/6 but not Cd93-/- LSCs in vitro suggesting that the ICD of CD93 regulates gene transcription via Scyl1 in CML LSCs. To discover compounds that affect LSC function similarly as genetic CD93 blockade, we performed a compound screen using the FDA approved drug library V2. The antiemetic agent metoclopramide, which is widely used in clinical routine to reduce nausea in cancer patients, was one very promising candidate identified in the screen. Metoclopramide treatment reduced clonogenic potential of CD93-competent LSCs to comparable levels as CD93-deficient LSCs in vitro without further affecting colony formation of CD93-deficient LSCs. Analysis of LSCs from newly diagnosed CML patients similarly demonstrated that CD93-signaling induces the expression of genes associated with proliferation and stemness, resulting in an increased clonogenic potential in vitro. In addition, colony formation and re-plating capacity in semisolid cultures of human CD34+CD38- LSCs was significantly impaired by metoclopramide at a pharmacological concentration of 0.1mM compared to control treatment. Conclusions: Overall, these results indicate that CD93-siganling is an important regulator of stemness and proliferation of human and murine CML LSCs. Furthermore, this study identifies expression of CD93 by LSCs as promising novel target for the treatment of CML. Disclosures Baerlocher: Novartis: Research Funding.

Preliminary evaluation of a novel blood test to predict delayed nausea for breast cancer patients.

e18210 Background: We have previously reported on glutathione recycling capacity (GRC) in red blood cells as a predictor of delayed nausea in cancer patients treated with platinum-based chemotherapies [1]. The test identifies individual variations in the efficiency to scavenge reactive oxygen species, produced by chemotherapy-induced cell-damage, which triggers release of serotonin – a know inducer of chemotherapy-induced nausea and vomiting. In this current study, we have examined if the GRC assay and/or changes in substance P (SP), another inducer of nausea, can predict delayed nausea among breast cancer patients receiving doxorubicin- or taxane-based therapies and thereby provide better guidance to individualized antiemetic therapies. Methods: Chemotherapy naïve breast cancer patients were asked to participate in this IRB-approved study. Consented patients donated a tube of blood prior to each treatment cycle. Commercial kits were used to measure GRC (OxPhos, Rockland Inc.) and Substance P (Parameter, R&amp;D Systems). On-set, duration and severity of nausea, and anti-emetics prescribed were documented by the medical staff. Results: Obtained GRC and SP values were compared to documented incidences of nausea. We found that 26.8% of taxane treated patients [N = 42] had moderate/severe nausea and demonstrated a similar GRC pattern to platinum-based induced nausea, i.e. low GRC results in more severe nausea. Among doxorubicin treated [N = 31] patients, 41.9% had moderate/severe nausea but showed no correlation with GRC. However, preliminary evaluation of these patients showed a continuous increase in SP levels (average 1.74 fold increase after one cycle). Conclusions: In this initial evaluation of our on-going study, we found that fewer patients had nausea in the taxane treated group with a similar GRC predictive pattern as previously reported. However, patients in the doxorubicin treated group were more likely to experience nausea with no correlation to GRC but with a steadily rising level of SP during the early part of their regimen. Using SP testing could help identify patients that might have a medical benefit from additional NK1 antagonist therapy. 1. Kutner, T., et al. Supprot Care Cancer (2017) 25:581-587.

Development of Zindol® through multi-center clinical trial for chemotherapy induced nausea and vomiting

Despite the widespread use of 5-HT3 receptor antagonist anti-emetics, chemotherapy induced nausea and vomiting (CINV) continues to be reported by up to 70% of adult patients and up to 58% of children receiving highly emetogenic chemotherapy agents. Nausea and vomiting are among the most distressing side effects of chemotherapy. Zindol® is an enhanced ginger product that is standardized by the bioactive constituents, gingerols and shogaols, of ginger (Zingiber officinale Roscoe). We utilized polarity-guided supercritical fluid fractionation SFS-CXF technology to establish conditions for the isolation of the active ingredients and then manufactured the API using SFS-CXP following cGMP. The API was then formulated to achieve a specific concentration of gingerols and shogaols with all-natural liquid excipients designed to maximize the stability and bioavailability of the bioactive constituents and encapsulated into gel capsules with a nitrogen head following cGMP. Zindol® was successfully evaluated in a multi-center, 644-patient, dose-finding, placebo-controlled, randomized Phase II/III clinical trial as an adjunctive therapy to conventional 5-HT3 anti-emetics for nausea in cancer patients undergoing chemotherapy (US Patent). We have since studied the MOA using a newly developed in vitro potency assay (US Patent Pending) and are planning to conduct a pivotal Phase III clinical trial for CINV and file an NDA with the FDA. A sister dietary supplement product, Zindol® DS, has been reported to be safe and effective in motion sickness, and nausea and vomiting related to pregnancy, elective surgery and medications. We plan to conduct rigorous clinical trials for these indications after NDA approval of Zindol® for CINV in adult and pediatric populations.

Effects of overshadowing on conditioned and unconditioned nausea in a rotation paradigm with humans.

We examine whether overshadowing by salient stimuli is effective in reducing the ability of a certain environment (the putative conditioned stimulus) to evoke conditioned nausea in healthy humans that experience nausea-evoking rotation (as the unconditioned stimulus, US) in that environment. Twenty-four rotation-susceptible subjects (12 males, 12 females) were randomly assigned to receive either overshadowing by salient tasting beverages (OS+), or a control treatment (a familiar beverage, water; OS-) prior to rotation on three consecutive days (acquisition). To control for taste experiences, the alternative beverage was consumed 12h later in the home environment (OS+: water, OS-: salient beverage). At Day 4 (test), all subjects drank the familiar beverage (water) prior to rotation (US). Rotation was standardized as 2×1-min rotation/day. Nausea was determined by a 7-item symptom scale measuring symptom number (SN) prior to (anticipatory), immediately after, and 15 and 30min after rotation and by the Nausea Profile (NP) questionnaire immediately after rotation. Cortisol and tumour necrosis factor (TNF)-α in saliva were sampled at the same time-points. SN and cortisol were also measured at home. Overshadowing reduced anticipatory (conditioned) SN. Post-rotation nausea (i.e. the unconditioned response) measured by the NP decreased within the OS+ group only. Anticipatory cortisol and TNF-α were not affected by overshadowing. Treatment × gender interactions manifested for post-rotation cortisol and TNF-α. Groups did not differ in SN and cortisol at home. Overshadowing is effective in reducing symptoms of anticipatory nausea and rotation-induced unconditioned nausea; its effect on endocrine and immunological parameters is gender specific. Its application in alleviation of anticipatory nausea in cancer patients is considered.

病態に応じた制吐薬の推奨を緩和ケアチームが行うことによる, がん患者の悪心に対する効果

病態に応じた制吐薬の推奨を緩和ケアチームが行うことによる, がん患者の悪心に対する効果

Δ9-Tetrahydrocannabinol targeting estrogen receptor signaling: the possible mechanism of action coupled with endocrine disruption.

Δ(9)-Tetrahydrocannabinol (Δ(9)-THC), a biologically active constituent of marijuana, possesses a wide variety of pharmacological and toxicological effects (e.g., analgesia, hypotension, reduction of inflammation, and anti-cancer effects). Among Δ(9)-THC's biological activities, its recognized anti-estrogenic activity has been the subject of investigations. Since Δ(9)-THC is used as both a drug of abuse (marijuana) and as a preventive therapeutic to treat pain and nausea in cancer patients undergoing chemotherapy in the United States and other countries (synthesized Δ(9)-THC; dronabinol), it is important to investigate the mechanistic basis underlying the anti-estrogenic activity of Δ(9)-THC. Since Δ(9)-THC has "no" binding potential for estrogen receptor α (ERα) which can be activated by estrogen (E2), the question of how Δ(9)-THC exerts its inhibitory effect on ERα is not resolved. We have recently reported that ERβ, a second type of ER, is involved in the Δ(9)-THC abrogation of E2/ERα-mediated transcriptional activity. Here we discuss the possible mechanism(s) of the Δ(9)-THC-mediated disruption of E2/ERα signaling by presenting our recent findings as well.

Ginger and its pungent constituents non-competitively inhibit activation of human recombinant and native 5-HT3 receptors of enteric neurons.

Beneficial effects of ginger in the treatment of gastrointestinal (GI) problems and chemotherapy-induced nausea and vomiting are well accepted. In rodents, the action of ginger seems to be mediated by the inhibition of 5-HT3 receptors, which are established targets to combat emesis and irritable bowel syndrome. Heterologously expressed human 5-HT3 A or 5-HT3 AB receptors were characterized by means of Ca(2+) influx studies using HEK293 cells. Complementing Ca(2+) measurements in Fluo-4-AM-stained whole-mount preparations of the human submucous plexus were carried out. Furthermore, [3H]GR65630 binding assays were performed to reveal the mode of action of ginger and its pungent compounds. We show for the first time that ginger extracts and its pungent arylalkane constituents concentration-dependently inhibit activation of human 5-HT3 receptors. Ginger extracts inhibited both receptors with increasing content of pungent compounds, confirming that these are part of ginger's active principle. Inhibition potencies of the arylalkanes 6-gingerol and 6-shogaol on both receptors were in the low micromolar range. A lipophilic ginger extract and 6-gingerol had no influence on 5-HT potency, but reduced the 5-HT maximum effect, indicating non-competitive inhibition. The non-competitive action was confirmed by [(3) H]GR65630 binding, showing that the ginger extract did not displace the radioligand from 5-HT3 A and 5-HT3 AB receptors. The potential relevance of the inhibitory action of ginger on native 5-HT3 receptors in the gut was confirmed in whole-mount preparations of the human submucous plexus. While a general neurotoxic effect of 6-gingerol was ruled out, it inhibited the 2-methyl-5-HT-mediated activation of 5-HT3 receptors residing on enteric neurons. Our findings may encourage the use of ginger extracts to alleviate nausea in cancer patients receiving chemotherapy and to treat functional GI disorders.

Nausea in cancer patients randomised to acupuncture or sham, compared to patients receiving standard care during radiotherapy

Nausea in cancer patients randomised to acupuncture or sham, compared to patients receiving standard care during radiotherapy

A qualitative study of the subjective experience of chemotherapy-induced nausea in cancer patients and survivors.

e19553 Background: Despite improvements in anti-emetics and reduction of chemotherapy-induced vomiting, nausea remains problematic. We hypothesize that a set of symptoms is identified by patients as nausea and these vary. Methods: Two groups of cancer patients (N = 42) with current or past experience of chemotherapy-induced nausea consented to semi-structured interviews about nausea, which were transcribed and analyzed. At interview, survivors were a median of 3.5 years (range 4 weeks – 15 y) post-treatment, median age 50 (range 25 – 80); current patients were being treated in an out-patient clinic, median age 54 (range 39 – 72). Both groups comprised 12 females and 9 males. Results: Across both groups, the nature, number, location, duration and intensity of experiences described as nausea varied; no single symptom was common to all descriptions. Physical and psychological symptoms sometimes but not always included dry-retching, vomiting, loss of appetite, indigestion, change of taste, dizziness, bloating, reflux, inability to concentrate, fatigue and physical restlessness. Location of nausea varied from head/neck, sternum, mid and lower abdomen and the whole body. Onset ranged from immediate to day 5 post-chemotherapy. Duration was from 1.5 hours to 6 months with conditioned stimuli continuing to trigger nausea 11 years post-treatment in one case. Intensity varied between and within, patients and successive treatments. For most, distinguishing features of chemotherapy-induced (as opposed to other) nausea were a constant presence over time, fatigue and emotional associations with the cancer diagnosis; for many, nausea negatively impacted on social and work interactions. Triggers also varied, and included food (smells), negative emotions including anxiety, movement, smells (e.g. hand-cream, cleaning products), treatment related events, tooth-brushing and mentioning nausea. Prescribed anti-emetics were consistently noted as reducing the intensity of, but for many, not completely alleviating, nausea; distraction and relaxation were preferred management techniques. Conclusions: Control of nausea will require personalized management of a range of physical and psychological symptoms.

The Interactions of the 5-HT3 Receptor with Quipazine-Like Arylpiperazine Ligands. The Journey Track at the End of the First Decade of the Third Millennium

The 5-HT(3) receptor (5-HT(3)R) occupies a special place among the serotonin receptor subtypes because it has been shown to be a ligand-gated ion channel, which is involved in a number of physiological functions and important pathologies. 5-HT(3)R antagonists have shown an outstanding efficacy in the control of the emesis induced by anticancer chemotherapy and few adverse side-effects, so as to revolutionize the treatment of nausea in cancer patients. This review covers the authors' work performed during the past decade in the development of 5-HT(3)R ligands belonging to the class of arylpiperazine derivatives related to quipazine (quipazine-like arylpiperazines, QLAs) and represents the extension of the review previously published in Current Topics in Medicinal Chemistry in 2002. The discussion is focused mainly on the most significant structure-affinity relationships emerged in the progress of the work and shows how the original ideas have evolved in the recent years.

Treatment of Chemotherapy-Induced Nausea in Cancer Patients.

For over 30 years, chemotherapy-induced nausea and vomiting have been the most severe and troublesome symptoms for cancer patients receiving chemotherapy. Unresolved chemotherapy-induced nausea and vomiting can lead to metabolic disorders, dehydration, nutritional depletion and esophageal tears, and can reduce patients' daily functioning and quality of life and interfere with treatment schedules.(1, 2) Despite the widespread use of antiemetics, chemotherapy-induced nausea continues to be problematic. Unlike vomiting, nausea is a subjective and unobservable phenomenon making it extremely difficult to accurately assess and treat. Current research suggests that management of chemotherapy-induced nausea should focus on treating the symptoms before they occur rather than after they develop. This review highlights evidence-based interventions for the treatment of chemotherapy-related nausea.

Ginger for chemotherapy-related nausea in cancer patients: A URCC CCOP randomized, double-blind, placebo-controlled clinical trial of 644 cancer patients

9511 Background: Despite the widespread use of antiemetics, post-chemotherapy nausea and vomiting continue to be reported by up to 70% of patients receiving chemotherapy. Ginger (Zingiber Officinale), an ancient spice, is used by practitioners worldwide to treat nausea and vomiting. We conducted a multi-site, phase II/III randomized, placebo-controlled, double-blind clinical trial to assess the efficacy of ginger for chemotherapy-related nausea in cancer patients at the University of Rochester-affiliated Community Clinical Oncology Program (CCOP) member sites. Methods: Cancer patients who experienced nausea following any chemotherapy cycle and were scheduled to receive at least three additional cycles were eligible. Patients were randomized into four arms: 1) placebo, 2) 0.5g ginger, 3) 1.0g ginger, or 4) 1.5g ginger. All patients received 5-HT3 receptor antagonist antiemetics on Day 1 of all cycles and took three 250mg capsules of ginger or placebo twice daily for six days starting three days before the first day of the next two cycles. Patients reported the severity of nausea during the morning, afternoon, evening, and night on a 7-point semantic rating scale (‘1' = ‘Not at all Nauseated' and ‘7' = “Extremely Nauseated”) for Days 1–4 of each cycle. The goal was to determine if ginger was more effective than placebo in controlling chemotherapy-related nausea in participants given a 5-HT3 receptor antagonist antiemetic. Results: A total of 644 patients were accrued (90% female, mean age = 53). Breast (66%), alimentary (6.5%), and lung (6.1%) cancers were the most common cancer types. Analysis of covariance (ANCOVA) examined change in nausea in the four study arms on Day 1 of cycles 2 and 3. All doses of ginger significantly reduced nausea (p=0.003). The largest reduction in nausea occurred with 0.5g and 1.0g of ginger. Also, time of day had a significant effect on nausea (p&lt;0.001) with a linear decrease over 24 hours for patients using ginger. Conclusions: Ginger supplementation at daily dose of 0.5g-1.0g significantly aids in reduction of nausea during the first day of chemotherapy. Supported by NCI PHS grants 1R25CA10618 and U10CA37420. No significant financial relationships to disclose.