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PubMed2000

Aspects of delayed chemotherapy-induced nausea. Dexamethasone and adrenal response patterns in patients and healthy volunteers.

Delayed chemotherapy-induced nausea is still a clinical problem, and the underlying mechanisms are poorly understood. Previous studies have suggested that corticosteroids are involved, although the mechanisms by which corticosteroids exert their antiemetic effect are largely unknown. We have previously found impaired control of delayed nausea after injection of dexamethasone. The possibility of differences in the recovery of the hypothalamic-pituitary-adrenal (HPA) axis after injection of dexamethasone was investigated in patients (n = 5) with gynaecological cancer being treated with platinum-based chemotherapy and in healthy female volunteers (n = 10). Urinary free cortisol was used to assess the levels of endogenous cortisol. Results showed that in both patients and controls injections of dexamethasone led to a significant decline in endogenous cortisol levels in 24 h and a subsequent significant recovery in the next 24 h. We conclude that the recovery of the HPA axis is rapid after a single dose of dexamethasone in patients and controls. The absence of an abnormal response pattern in patients makes it probable that the suppression and recovery of the HPA axis after injection of dexamethasone does not influence the corticosteroid-induced rebound effect on delayed platinum-induced nausea.

Aged↗
PubMed1997

Ondansetron versus a chlorpromazine and dexamethasone combination for the prevention of nausea and vomiting: a prospective, randomised study to assess efficacy, cost effectiveness and quality of life following single-fraction radiotherapy.

Lower hemibody radiotherapy is an effective palliative treatment for patients with wide-spread bone metastases, but is frequently associated with the unpleasant side effects of nausea and vomiting. Patients often require admission to hospital for at least an overnight stay, with its inevitable costs. This study has investigated the clinical efficacy and safety profile of ondansetron, a 5HT3 receptor antagonist, and compared it to a standard antiemetic combination, chlorpromazine and dexamethasone. Sixty-six patients were randomised to receive antiemetic prophylaxis with either oral ondansetron or a combination of chlorpromazine and dexamethasone (33 patients in each arm): 60 were treated with lower abdominal radiotherapy (8 Gy mid-plane dose) and 6 with radiotherapy to the upper lumbar spine (12.5 Gy incident dose). Patients were assessed for severity of nausea and vomiting and for whether they would use the same antiemetic again. Quality of life was assessed using the Functional Living Index Cancer (FLIC) and Functional Living Index Emesis (FLIE) quality-of-life questionnaires. A detailed cost-benefit analysis was also performed. Ondansetron scored highly as an antiemetic, being significantly better at controlling emesis on all four study days (P < 0.001) and significantly better at controlling nausea on day 1 (P < 0.001) than the standard combination of chlorpromazine and dexamethasone. Quality of life was better in the ondansetron-treated group, and ondansetron was found to be safe with no significant adverse effects. As a result, 98% of patients and investigators would use ondansetron again. Cost-benefit analysis revealed that, when complete control of emesis is the aim, ondansetron is not unduly expensive compared to the standard antiemetic regimen. As ondansetron was clearly effective in patients receiving hemibody irradiation it seems it would be prudent to adopt it for use in such patients routinely. The use of ondansetron would allow them to be treated as outpatients, with the attendant financial and psychosocial benefits of such an approach.

Adult↗
PubMed1998

Rationale for the use of a single fixed intravenous dolasetron dose for the prevention of cisplatin-induced nausea and vomiting. Pooled analysis of 14 clinical trials.

Dolasetron mesilate is a selective 5-HT3 receptor antagonist that prevents chemotherapy-induced and postoperative nausea and vomiting. For the majority of patients in intravenous dolasetron trials for chemotherapy-induced nausea and vomiting, dosing has been based on body weight (mg/kg). The approved weight-based dose is 1.8 mg/kg based on results of controlled clinical trials. However, trials of dolasetron evaluating oral doses for prevention of chemotherapy-induced emesis, and intravenous doses for prevention and treatment of postoperative emesis have used a fixed milligram dose. To identify an appropriate intravenous fixed milligram dose for the prevention of chemotherapy-induced nausea and vomiting, this analysis was performed to derive efficacy results for fixed milligram doses from pooled results obtained with dosing based on body weight. Intravenous dolasetron doses for 1,598 patients treated on a mg/kg basis (0.3, 0.6, 1.2, 1.8, 2.4, 3.0 and 5.0 mg/kg) in 14 clinical trials were converted to fixed milligram doses based on weight. Fixed-dose groups were established at doses of 50, 75, 100, 125, 150, and 200 mg. Doses less than or equal to the midpoint between two dose groups were included in the lower dose group. Pooled results showed that the 100 mg intravenous dolasetron dose group (who received actual doses of 88-112 mg) produced the highest rate (53%) of complete response (0 emetic episodes and no rescue medication in the 24-h period following initiation of chemotherapy).

Adolescent↗
PubMed2000

A double-blind, randomised, parallel study comparing intravenous dolasetron plus dexamethasone and intravenous dolasetron alone for the management of fractionated cisplatin-related nausea and vomiting.

Fractionated cisplatin-containing regimens are routinely used for chemotherapy in certain types of cancer. Dolasetron has been shown to be effective in preventing acute emesis related to high-dose cisplatin chemotherapy over 24 h; its effectiveness has not been evaluated in fractionated cisplatin-containing chemotherapy. This trial was designed to assess the efficacy of dolasetron alone or dolasetron plus dexamethasone in preventing nausea and vomiting related to fractionated cisplatin chemotherapy. The patients were 210 cancer in-patients, who were randomised to receive 100 mg dolasetron i.v. or 100 mg dolasetron i.v. plus 20 mg dexamethasone before chemotherapy primarily with cisplatin (15-50 mg/m2) infused over < or =4 h for at least 2 but not more than 5 consecutive days. Dolasetron was administered to all patients 30 min before cisplatin. Dexamethasone was administered in double-blind fashion 5 min before cisplatin. Efficacy was measured at hour 24 of each study day using complete response (no vomiting and no rescue medication) and maximum severity of nausea, self-assessed by patients using a 100mm visual analogue scale. Most (198) of the patients completed the study and were evaluable. Overall complete response rates were significantly higher in the dolasetron plus dexamethasone group than in the dolasetron only group (72.9% vs. 40.8%, respectively; P<0.0001). Complete response rates on each study day were also significantly higher with dolasetron plus dexamethasone than with dolasetron alone (P<0.029), with an attenuated efficacy in the delayed phase in both groups. Chi-square test and logistic regression applied to daily response rates indicated a significant influence of treatment (day 1: P = 0.0002, day 2: P<0.0001, day 3: P = 0.0007, day 4: P = 0.0007, day 5: P = 0.029). Treatment and duration of chemotherapy exerted the only statistically significant subgroup effects on complete response (P<0.0001). Both treatments were administered safely. As seen with other 5-HT3 receptor antagonist antiemetics, the addition of dexamethasone to dolasetron significantly increases effectiveness in preventing nausea and vomiting related to fractionated cisplatin chemotherapy. Both dolasetron and dolasetron plus dexamethasone were well tolerated.

Adult↗
PubMed2006

Omission of fentanyl during sevoflurane anesthesia decreases the incidences of postoperative nausea and vomiting and accelerates postanesthesia recovery in major breast cancer surgery.

PURPOSE: Our purpose was to investigate the effect of omission of fentanyl during sevoflurane anesthesia on the incidences of postoperative nausea and vomiting and on postanesthesia recovery in female patients undergoing major breast cancer surgery. METHODS: Female patients (American Society of Anesthesiologists [ASA] physical status [PS] class I-II; age, 28-84 years) undergoing major breast cancer surgery were randomized to one of two anesthesia maintenance groups: sevoflurane-fentanyl anesthesia (SF; n = 25) or fentanyl-free sevoflurane anesthesia (S; n = 26). All patients were administered with propofol 2 mg x kg(-1) intravenously for anesthesia induction, a laryngeal mask airway was placed, and they received rectal diclofenac and local infiltration anesthesia. Anesthesia was maintained with sevoflurane in oxygen-air and they breathed spontaneously. The patients in group SF received fentanyl 0.1 mg intravenously and those in group S received normal saline during anesthesia. RESULTS: Group SF revealed higher incidences of postoperative nausea (68% vs 27%) and vomiting (32% vs 8%) in the first 24 postoperative hours than group S. The median (25th-75th percentile) length of time from postanesthesia care unit (PACU) admission to ambulation was significantly longer in group SF (n = 23) at 195 min (158-219 min), than in group S, at 141 min (101-175 min). Two patients in group SF could not walk during the PACU stay. CONCLUSION: Omission of fentanyl during sevoflurane anesthesia, combined with diclofenac and local infiltration anesthesia, decreases the incidences of postoperative nausea and vomiting and accelerates postanesthesia recovery in patients undergoing major breast cancer surgery.

Aged↗
PubMed1994

TCDD-induced hypophagia is not explained by nausea.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most potent known anorexigens with an unestablished mechanism of action. In the present study, the role of nausea in TCDD-induced hypophagia was assessed by a battery of behavioral (conditioned taste aversion [CTA], kaolin consumption, protein selection), biochemical (plasma oxytocin), and antiemetic drug intervention (trimethobenzamine, metoclopramide) approaches. Moreover, both the most TCDD-susceptible (Long-Evans [L-E]; IP LD50 approximately 10 micrograms/kg) and the most TCDD-resistant (Han/Wistar [H/W]; IP LD50 > 3000 micrograms/kg) rat strains were employed in the experiments. L-E rats were exposed to a lethal dose of TCDD (50 micrograms/kg), whereas H/W rats were treated with high but nonlethal doses (50 or 1000 micrograms/kg). TCDD produced a positive CTA response in H/W rats alone. These animals also increased their kaolin consumption more than L-E rats of either gender after TCDD exposure. TCDD decreased the proportional intake of energy from high-protein diet in female L-E rats, but tended to increase it in male L-E and H/W rats. TCDD did not affect plasma oxytocin concentration by itself, but potentiated the elevation caused by the positive control compound, LiCl, in L-E rats on day 8. Neither antiemetic tested had any detectable influence on TCDD-induced wasting. These findings imply that the degree of nausea elicited by TCDD in the rat depends on strain and gender. However, nausea has only a minor, if at all, causal role in the lethal wasting syndrome characteristic of this compound.

Animals↗
PubMed1989

Advances in the management of nausea and vomiting induced by non-cisplatin containing chemotherapeutic regimens.

Nausea and vomiting are the most feared toxicities of chemotherapy. Afferent impulses from the chemoreceptor trigger zone, peripheral sites, the cerebral cortex, or the vestibular center can initiate the emetic reflex. Antiemetic protection therefore requires interruption of appropriate emetogenic pathways. Since the chemoreceptor trigger zone contains numerous dopaminergic neurons, antidopaminergic agents including phenothiazines and metoclopramide have gained importance as antiemetics. However standard dose phenothiazines have limited efficacy while high dose metoclopramide may have excessive toxicity in the non-cisplatin setting. Recent advances have therefore centered on development of new classes of antiemetics. Corticosteroids have excellent activity alone or in combination with other antiemetic agents. Cannabinoids have recently been introduced into commercial use as antiemetics with particular activity against non-cisplatin chemotherapy. Benzodiazepines are active against anticipatory nausea and vomiting and are also used in combination antiemetic regimens. Although the vestibular center seems to have a lesser influence on chemotherapy-induced nausea and vomiting, vestibular blocking agents such as scopolamine may have a potential role as adjunctive antiemetics. Finally, appreciation of the role of serotonin (5-HT3) receptors in both peripheral and central emetic pathways may lead to a new class of antiserotonergic antiemetic agents.

Adrenal Cortex Hormones↗
PubMed1990

A comparison of ondansetron with metoclopramide in the prophylaxis of chemotherapy-induced nausea and vomiting: a randomized, double-blind study. International Emesis Study Group.

The efficacy of ondansetron was compared with metoclopramide in the prophylaxis of nausea and vomiting induced by cyclophosphamide greater than or equal to 500 mg/m2 in combination with doxorubicin greater than or equal to 40 mg/m2 or epirubicin greater than or equal to 40 mg/m2. complete anti-emetic protection in the 24 h following chemotherapy was achieved in 26 of 40 (65%) patients treated with ondansetron compared with 17 of 42 (41%) patients treated with metoclopramide. Severe nausea was present in 3% of patients in the ondansetron group and 31% in the metoclopramide group. A worst day analysis of control of emesis and nausea on days 2 and 3 following chemotherapy also demonstrated ondansetron to be more effective than metoclopramide. Both treatments were well tolerated. Ondansetron is more effective as an anti-emetic than metoclopramide in this type of cytostatic therapy.

Adult↗
PubMed1991

Dronabinol and prochlorperazine in combination for treatment of cancer chemotherapy-induced nausea and vomiting.

Dronabinol (Marinol, Roxane Laboratories, Columbus, OH) and prochlorperazine were tested alone and in combination in a randomized, double-blind, parallel group, multicenter study. Patients were randomized to receive either 1) dronabinol 10 mg every 6 hr plus placebo; 2) placebo plus prochlorperazine 10 mg every 6 hr; or 3) dronabinol and prochlorperazine, each 10 mg every 6 hr. Antiemetic treatment was begun 24 hr prior to and continued for 24 hr after the last dose of chemotherapy; all was given orally. Only 29% of patients in group 3 versus 47% in group 1 and 60% in group 2 experienced nausea after chemotherapy. In addition, the median duration per episode and severity of nausea were significantly less with combination therapy. Vomiting occurred after chemotherapy in 41%, 55%, and 35% of patients in groups 1, 2, and 3, respectively. The median duration per episode of vomiting was 1 min in group 3 versus two in group 1 and four in group 2. Side effects, primarily CNS, were more common in group 1 than in group 2; addition of prochlorperazine to dronabinol appeared to decrease the frequency of dysphoric effects seen with the latter agent. The combination was significantly more effective than was either single agent in controlling chemotherapy-induced nausea and vomiting.

Adult↗
PubMed1991

Transdermal scopolamine use in the control of narcotic-induced nausea.

Nausea affects from 40% to 70% of cancer patients who received narcotics to manage their pain. This occurs more frequently when they are ambulatory than when they are recumbent and may be the result of narcotic-enhanced labyrinthine sensitivity to motion. Scopolamine has previously been found to be an effective antiemetic for motion sickness. In a prospective pilot study, 9 (69%) of 13 cancer patients experienced rapid relief of their narcotic-induced nausea when they used Scopolamine Transderm-V patches alone. Only two patients experienced side effects with the scopolamine, and in one patient, the side effects may have been dose related. Although tolerance to the increased vestibular sensitivity may occur, this was not universal. Further prospective trials are necessary to establish whether transdermal scopolamine is useful in controlling the narcotic-induced nausea experienced by cancer patients.

Administration, Cutaneous↗
PubMed1991

Development of a behavioral measure of mouth pain, nausea, and wellness for patients receiving radiation and chemotherapy.

Toxicities from the chemotherapy and irradiation preparative regimen for bone marrow transplantation include nausea, emesis, and oral pain. Behavioral measures were developed as alternatives to paper and pencil measures of these symptoms because patients are sometimes too ill, unavailable, or unwilling to complete self-report scales. Behavioral observations also provide supplements to self-report for these multidimensional symptoms. For 24 days during the acute phase of transplantation, nurses rated the behavior of adult patients on: (a) oral pain (for example, requests pain medication or refuses mouth examination), (b) nausea (for instance, retches or keeps emesis basin near), (c) wellness (for example, talks voluntarily or smiles), (d) verbal complaints of pain, and (e) verbal complaints of nausea. The behavioral measures demonstrated good interday reliability (range, 0.70-0.86) and construct validity as demonstrated by a multitrait, multimethod correlation matrix.

Adult↗
PubMed1995

Chemotherapy-induced nausea and emesis in pediatric cancer patients: an analysis of coping strategies.

We investigated the preference and perceived efficacy of coping strategies used to manage chemotherapy-induced nausea and emesis in 57 pediatric oncology patients. Over 85% of children preferred "Wishful Thinking," "Emotional Regulation," and "Distraction" to cope with nausea, and "Emotional Regulation" to manage emesis. Stepwise logistic regression analyses revealed that the coping strategy used and its perceived efficacy depended upon patient age and gender, severity of symptom distress, time elapsed from last chemotherapy, experience, and whether nausea or emesis was the identified problem. Successful copers, defined as those reporting high coping efficacy and minimal distress, composed only 25% of the sample. These children most often used "Problem Solving" combined with "Social Support" for symptom management. Successful coping was also associated with lower emetogenic potential of chemotherapy. The significance of these results is discussed for identifying high-risk children who may benefit from coping interventions.

Adaptation, Psychological↗
PubMed1994

Tropisetron compared with a metoclopramide-based regimen in the prevention of chemotherapy-induced nausea and vomiting.

This randomised, open, parallel group study compared the antiemetic efficacy and tolerability of tropisetron with metoclopramide plus lorazepam in 102 patients receiving a first course of non-cisplatin-containing chemotherapy. Control of acute vomiting by tropisetron was significantly superior to that of the metoclopramide regimen, with total control (no vomiting) in 45% of 51 patients in the tropisetron group compared with 22% of 51 patients in the metoclopramide group (P = 0.013); total and partial control (< 5 vomits) occurred in 67 and 47% of patients, respectively (P = 0.044). The incidences of acute nausea and of delayed nausea and emesis were similar in the two treatment groups. Both tropisetron and metoclopramide were well tolerated; no adverse effects were attributed to tropisetron administration with the exception of headache. One patient in the metoclopramide group reported confusion and tremor thought to be related to the antiemetic therapy. Tropisetron is an effective and well-tolerated agent in the prevention of chemotherapy-induced vomiting. The control of acute nausea was similar in the two treatment groups, but tropisetron was superior to a metoclopramide-based regimen in the control of acute vomiting.

Acute Disease↗
PubMed2006

Conditioned gaping in rats: a selective measure of nausea.

When intraorally infused with a flavored solution previously paired with an emetic drug, rats display a characteristic gaping reaction that reflects conditioned nausea in this species that is unable to vomit. The commonly used conditioned taste avoidance measure, is not a selective measure of nausea because nearly every drug tested (even rewarding drugs) is capable of producing a conditioned taste avoidance. In contrast, only emetic drugs produce conditioned gaping reactions in rats, and anti-emetic drugs interfere with the establishment and the expression of conditioned gaping reactions but do not interfere with conditioned taste avoidance. The conditioned gaping reaction can be used as a pre-clinical tool to evaluate the side effects of nausea that might result from newly developed pharmaceutical agents.

Animals↗
PubMed2005

Chemotherapy-induced nausea and vomiting: current and new standards in the antiemetic prophylaxis and treatment.

Nausea and vomiting are considered as two of the most distressing side-effects of chemotherapy. Chemotherapy-induced nausea and vomiting have been classified into acute, delayed and anticipatory based on the time of onset. The frequency of nausea and vomiting depends primarily on the emetogenic potential of the chemotherapeutic agents used. With the introduction of the 5-HT3 receptor-antagonists in combination with dexamethasone in the early 1990s approximately 70% of patients receiving highly emetogenic chemotherapy were protected from acute emesis. However, 40% of patients have symptoms in the delayed phase. Another group of antiemetics, the neurokinin-1-receptor-antagonists, have recently been introduced. The addition of neurokinin receptor (NK1 receptor)-antagonists to standard therapy significantly improves emesis protection in the acute and in particular in the delayed phase by approximately 20%. Due to these new developments, revised antiemetic guidelines have been set. Here, the most recent developments in antiemetic therapy, including these guidelines, are reviewed.

Acute Disease↗
PubMed2006

Symptom experiences during chemotherapy treatment--with focus on nausea and vomiting.

Nausea and vomiting are common and well-studied symptoms in cancer care. Most previous studies have focused on the frequency and management of these symptoms. The aim of the study was to acquire a deeper understanding of cancer patients' symptom experiences with a focus on nausea and vomiting during chemotherapy treatment, and the consequences these have on their daily lives. Nine women with different types of cancer and chemotherapy treatments were admitted for chemotherapy treatment and participated in the study. Semi-structured interviews were conducted and analysed using content analysis inspired by Kvale's methods of clarifying and developing new meaning. Five main categories were identified as "before cancer diagnosis", "being ill--consequences on daily life", "going through chemotherapy treatment", "coping with treatment" and "after treatment--looking forward to a normal life". The present findings suggest that the individual experiences of nausea and vomiting during chemotherapy treatment may have a profound effect on how treatment is perceived and may influence future decisions concerning further treatment.

Activities of Daily Living↗
PubMed2006

Prophylaxis of postoperative nausea and vomiting: controversies in the use of serotonin 5-hydroxytryptamine subtype 3 receptor antagonists.

Postoperative nausea and vomiting (PONV) continues to be a "big little problem" despite recent advances in anesthesia. Because of an increased interest in, and the abundant publications on this topic, guidelines for the management of PONV were published in 2003. Several key but controversial issues regarding PONV prophylaxis were left unaddressed, however. These included whether clinical differences exist between the 5-hydroxytryptamine subtype 3 (5-HT3) receptor antagonists, concern over optimal dosage and timing of administration, optimal 5-HT3 receptor antagonist combination therapy, and whether rescue therapy is effective after prior administration of the same or a different 5-HT3 receptor antagonist. The application of these antiemetics in clinical practice has raised questions regarding the role of the 5-HT3 receptor antagonists in the treatment of postdischarge nausea and vomiting and opioid-induced nausea and vomiting. A brief overview of the incidence, risk factors and current management recommendations for PONV and current controversies with special emphasis on the 5-HT3 receptor antagonists, is discussed.

Analgesics, Opioid↗
PubMed2005

National Institutes of Health grant awards for pain, nausea, and dyspnea research: an assessment of funding patterns in 2003.

UNLABELLED: We introduce an interactive database that permits description and exploration of National Institutes of Health (NIH) funding patterns for research on pain, nausea, and dyspnea. The database encompasses both basic science and clinical research. This article describes how we created the database, including the procedures we developed for reviewing and classifying research grants. In addition, it reports NIH grants and funding activity for the year 2003, with a breakdown of funding activity by Institute and funding comparisons across Institutes. It also describes a first attempt to identify clinically significant but underfunded research domains. In 2003, the NIH funded 1148 grants having relevance to the domain of pain, representing 2.5% of the total NIH research budget. Of those, 581 grants, or about 1% of the NIH budget, had a primary focus on pain. Of the diseases and conditions addressed by the current implementation, musculoskeletal conditions were the best represented with 105 grants, whereas cardiac conditions had the fewest number of grants with 7. The NIH funded 43 grants for dyspnea research and a scant 29 grants for nausea studies. We discuss the current limitations of the database and our plans for further development. PERSPECTIVE: The interactive database and classification system for pain, nausea, and dyspnea research funded by the NIH reported on in this article represents an objective and verifiable resource for health policy makers and others interested in NIH funding decisions. The high inter-rater reliability achieved attests to the objectivity of the classification method. Initial analyses demonstrate that these data can usefully track funding patterns by NIH institutes and reveal underfunded areas of research.

Budgets↗