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Antiemetic activity of high-dose metoclopramide combined with methylprednisolone versus metoclopramide alone in dacarbazine-treated cancer patients. A randomized double-blind study of the Italian Oncology Group for Clinical Research.

In a double-blind randomized trial, we compared the efficacy and tolerability of high-dose (2 mg/kg X 4) intravenous metoclopramide (MTC) versus metoclopramide plus high-dose (250 mg X 2) intravenous methylprednisolone (MP) administered for the first 2 days in untreated patients submitted to dacarbazine chemotherapy for 5 days. Thirty-four patients entered the study. Complete protection from nausea and vomiting was achieved in the majority of patients all through the study period with both antiemetic treatments, with slightly greater efficacy at day 2 for the combination. However, after suspension of the antiemetic therapy, there was a relapse of vomiting in patients. Side effects were not different between the two treatments, but extrapyramidal reactions were significantly increased on the second day of antiemetic therapy. In conclusion, high-dose MTC with or without MP can give good antiemetic protection and the combination seems to be slightly more efficacious. However, the relapse of vomiting after discontinuing antiemetic treatment and the high incidence of extrapyramidal reactions justify further studies to find a better antiemetic treatment.

Dacarbazine↗

Prolongation of the antiemetic action of P6 acupuncture by acupressure in patients having cancer chemotherapy.

Previous work from our department has shown that P6 acupuncture is an effective adjuvant to conventional antiemetic therapy for patients having cytotoxic drugs. However, its efficacy is limited to about 8 h. The current studies show that the application of an elasticized wrist band with a stud placed over the acupuncture point, and pressed regularly every 2 h, will prolong the antiemetic action for 24 h. This proved more effective in hospitalized patients (20/20) than in outpatients (15/20), presumably due to the encouragement given to regularly press the stud. Nausea and vomiting remain problems with cancer chemotherapy despite the use of antiemetics. Following encouraging results with P6 acupuncture (ACP) in postoperative sickness this has been shown to be effective in cancer chemotherapy in 105 patients who, despite the use of conventional antiemetics had been sick following the previous treatment. Electrical stimulation (10 Hz DC) of P6 point for 5 min before administration of the cytotoxic drugs was effective in preventing sickness in 66% and only 6% got no benefit. The ACP was given with the antiemetics which the patients had been receiving. Although there were no side effects with the ACP, the benefit only lasted 6-8 h. This was not important in hospitalized patients where the treatment could be repeated, but was a problem with outpatients. It has been shown that pressure on the P6 point (acupressure) has an antiemetic action. A commercially available elasticized band with a plastic stud (Sea Band) is an effective method of applying pressure to P6 point.(ABSTRACT TRUNCATED AT 250 WORDS)

Acupuncture Therapy↗

Antiemetic efficacy of prochlorperazine, haloperidol, and droperidol in cisplatin-induced emesis.

The antiemetic efficacy of haloperidol, droperidol, and prochlorperazine in preventing cisplatin-induced emesis was evaluated. Twenty-seven patients receiving 51 courses of cisplatin chemotherapy randomly received antiemetic treatment with prochlorperazine (6 mg/sq m), droperidol (1 mg/sq m), or haloperidol (1 mg/sq m) in a double-blind crossover study. Antiemetics were given by intramuscular injection one hour before beginning cisplatin and every three hours thereafter for a total of six doses. The number of emetic episodes, volume of emesis, and duration of the emetic episodes were monitored by oncology nurses. There were no significant differences in the median number of emetic episodes among antiemetic treatments: 3.5 for prochlorperazine, 4.0 for haloperidol, and 3.0 for droperidol. There were also no significant differences among the antiemetics in the median volume of emesis or the median duration of the emetic episodes. At the doses used in this study, the antiemetic efficacy of prochlorperazine, droperidol, and haloperidol appear to be comparable for patients receiving cisplatin chemotherapy.

Aged↗

Oral combination antiemetics in patients with small cell lung cancer receiving cisplatin or cyclophosphamide plus doxorubicin.

BACKGROUND: Intravenous antiemetic combinations containing a 5-HT3 receptor antagonist (like metoclopramide, ondansetron, or granisetron) with dexamethasone have become the standard therapy for the treatment of acute chemotherapy-induced vomiting. Intravenous antiemetics, however, can be more costly and take more time to prepare and deliver, and therefore are not preferred for home, outpatient, or office use. The objective of this study was to determine the antiemetic activity and safety of the oral combination antiemetic regimen of metoclopramide, dexamethasone, and diphenhydramine in patients with small cell lung cancer receiving standard outpatient chemotherapy programs. METHODS: Fifty-two patients receiving initial cisplatin (60 mg/m2) or cyclophosphamide (600-1500 mg/m2) plus doxorubicin (30-45 mg/m2) received an oral regimen of metoclopramide (3 mg/kg x 2 then 2 mg/kg x 2 or 4 doses), dexamethasone (20 mg) and diphenhydramine (50 mg x 2 or 3 doses) (oral MDD), beginning 30 minutes before chemotherapy. RESULTS: Vomiting was prevented in 15 of 21 (76%) patients (95% confidence interval [CI], 53%-92%) receiving cisplatin and 21 of 31 (71%) individuals (95% CI, 52%-86%) given cyclophosphamide plus doxorubicin. Adverse effects were mild and transient and included sedation, loose stools, akathisia, and hiccoughs. CONCLUSIONS: The oral MDD antiemetic regimen prevented acute emesis in 73% of the patients entered and was well tolerated in this population of patients with small cell lung cancer.

Administration, Oral↗

Clinical trials with antiemetic agents in cancer patients receiving chemotherapy.

Vomiting accompanied by nausea is a serious acute toxicity which occurs after chemotherapy with virtually every class of cancer chemotherapeutic agents. The inability to adequately alleviate this toxicity may lead to serious complications such as general malaise, weight loss, and electrolyte imbalance. We have reviewed 34 studies in which more than 2200 cancer patients were administered 25 different antiemetics for treatment of chemotherapy-induced vomiting. All patients received a variety of cancer chemotherapeutic agents given either as single agents or in combination. The antiemetic agents included phenothiazines, antihistamines, anticholinergics, benzoquinolizines, barbiturates, butyrophenones, procainamides, cannabinoids, steroids, and benzodiazepines. It is apparent from these studies that the use of conventional antiemetic agents for treating cancer chemotherapy-induced vomiting is of marginal value, and the use of investigational antiemetic agents show conflicting results as to efficacy. More quantitative measures for evaluating emesis need to be defined, and the implications that a particular antiemetic therapy may be efficacious for some but not all classes of cancer chemotherapeutic agents need to be evaluated.

Antiemetics↗

Antiemetic effect of intramuscular levonantradol in patients receiving anticancer chemotherapy.

Positive results of investigations of the antiemetic activity of delta-9-tetrahydrocannabinol (THC) in patients receiving cancer chemotherapy have led to the development of levonantradol, a synthetic derivative of THC. We assessed both the antiemetic activity and toxicity of intramuscular levonantradol in patients receiving cancer chemotherapy who were refractory to conventional antiemetic therapy. An open dose-finding study was conducted using initial doses of 0.5 mg. Doses were escalated by 0.5 mg when an incomplete response with no toxicity was observed. Of the 28 patients initially treated, 25/28 (89 per cent) achieved a complete or partial antiemetic response at doses ranging from 0.5 to 1.5 mg. There was no difference in response rate with respect to age or patient size. Of the 31 patients evaluable for toxicity, six reported none. Dysphoria, the dose-limiting toxicity, occurred in five patients (16 per cent) at 1.0 to 1.5-mg doses. The most commonly reported side effects were somnolence (48 per cent) and dry mouth (32 per cent). We conclude that intramuscular levonantradol is an effective antiemetic at doses as low as 0.5 mg.

Adolescent↗

Randomized crossover study of the antiemetic activity of levonantradol and metoclopramide in cancer patients receiving chemotherapy.

In a randomized crossover study 57 cancer patients receiving chemotherapy with high emetic potential were treated with low-dose levonantradol or standard-dose metoclopramide and crossed over to the other antiemetic drug in the next identical chemotherapy cycle. In the 45 patients evaluable for treatment response the antiemetic efficacy of levonantradol was significantly better: 62% had less nausea and 58% less vomiting, as against 11% and 16%, respectively, with metoclopramide. Patient preference for antiemetic treatment was levonantradol in 49% and metoclopramide in 22% of cases. Levonantradol treatment was accompanied by a relatively high incidence of side-effects (71%) compared with metoclopramide (29%). The antiemetic efficacy of each single drug was incomplete in most cases of this trial, and antiemetic combination therapy is recommended for further trials.

Adolescent↗

Antiemetics in children receiving cancer chemotherapy.

Nausea and vomiting are debilitating side effects that often accompany the administration of chemotherapy and may lead to adverse physiological and psychological effects. Chemotherapy agents usually stimulate the chemoreceptor trigger zone, which then sends signals to the vomiting center in the medullary lateral reticular formation. The neurochemistry of vomiting involves serotonin and serotonin S3 receptors. Nausea and vomiting are difficult to treat once they have occurred, and prior poor antiemetic control may lead to future anticipatory nausea and vomiting. Thus, good antiemetic regimens must be prophylactic, scheduled, and individualized. Specific regimens must be adjusted to account for the emetogenic potential of the chemotherapy drug(s) being administered and the individual patient's preferences. The major classes of antiemetics include serotonin S3 receptor antagonists, phenothiazines and metoclopramide. Steroids are ineffective antiemetics alone but good potentiators of other antiemetics. We usually recommend a serotonin S3 receptor antagonist alone for less emetogenic regimens or in conjunction with dexamethasone for more emetogenic regimens. For breakthrough vomiting, we usually add lorazepam and/or scopolamine.

Antiemetics↗

Dose-ranging evaluation of the antiemetic efficacy of intravenous dolasetron in patients receiving chemotherapy with doxorubicin or cyclophosphamide.

Selective 5-HT3 antagonists have proven to be safe and effective for the prevention of chemotherapy-induced nausea and vomiting. Dolasetron is a new highly selective addition to this class of antiemetics that has been shown to have significant antiemetic activity in patients receiving cisplatin-containing regimens. This pilot study was designed to evaluate the antiemetic efficacy of dolasetron in cancer patients receiving doxorubicin and/or cyclophosphamide. This study used an open-label, non-randomized design to evaluate the efficacy and safety of intravenous dolasetron in the prevention of emesis in patients receiving doxorubicin (25-75 mg/m2) and/or cyclophosphamide (400-1200 mg/m2). Sixty-nine patients received a single, intravenous dose of dolasetron over 15-20 min beginning 30 min prior to the start of chemotherapy. Dose levels of dolasetron studied were: 0.3, 0.6, 1.2, 1.8 and 2.4 mg/kg. Patients were monitored for emesis, nausea and adverse events for 24h after the start of chemotherapy. Overall, 61% of patients experienced complete control of emesis. No significant trend towards increased antiemetic efficacy (P = 0.076) or nausea control with increasing dolasetron dose was noted, although the power to detect significant differences was limited by the small number of patients on the 0.3-mg/kg and 2.4-mg/kg dose levels. Age, gender, and type of chemotherapy were significant predictors of complete antiemetic control. Adverse events were generally mild and included headache, chills, lightheadedness, fever, diarrhea, dizziness, and asymptomatic prolongation of ECG intervals. Intravenous dolasetron is safe and effective in the prevention of emesis induced by doxorubicin and/or cyclophosphamide.

Adult↗

Prophylactic antiemetic therapy with ondansetron, tropisetron, granisetron and metoclopramide in patients undergoing laparoscopic cholecystectomy: a randomized, double-blind comparison with placebo.

PURPOSE: Postoperative nausea and vomiting (PONV) is a distressing adverse effect of general anaesthesia. The aim of the current study was to compare the antiemetic activity of different 5-hydroxytryptamine3 receptor antagonists with that of metoclopramide and placebo. METHODS: In a prospective, randomized, double-blind study we have compared the antiemetic activity of the prophylactic administration of ondansetron 4 mg, tropisetron 5 mg and granisetron 3 mg with that of metoclopramide 10 mg and placebo in 132 patients undergoing laparoscopic cholecystectomy. All study drugs and placebo were given as a short iv infusion ten minutes before the induction of anaesthesia. Perioperative anaesthetic care was standardized in all patients. Nausea and vomiting were assessed by direct questioning of the patient at 1, 4, 9, 12, 18 and 24 hr after recovery from anaesthesia. If patients experienced nausea and/or vomiting, rescue antiemetic treatment (metoclopramide 10 mg iv) was administered. RESULTS: For the 24-hr recovery period after surgery, the percentages of emesis-free patients were 65.5%, 52%, 48%, 29.2% and 27.6% in the ondansetron, granisetron, tropisetron, metoclopramide and placebo groups, respectively. Prophylactic antiemetic treatment with ondansetron resulted in a lower incidence (P = 0.02) of PONV than with metoclopramide or placebo. The times at which rescue antiemetic was first received were longer (P < 0.01) in ondansetron group than in the placebo and metoclopramide groups. There were no statistical differences between ondansetron, tropisetron and granisetron groups. CONCLUSIONS: Ondansetron, when given prophylactically resulted in a significantly lower incidence of PONV than metoclopramide and placebo. Metoclopramide was ineffective.

Adult↗

Antiemetic guidelines: creating a more practical treatment approach.

Antiemetic guidelines from a variety of professional organizations have been available for several years. It is unclear just how often these guidelines have been used, however; data indicate that some practitioners still do not treat their patients according to the recommendations. Some of those involved in the creation of the original guidelines convened to try to create a simpler, more practical approach to the use of antiemetics in preventing chemotherapy-induced nausea and vomiting. The group's intention was to clarify available guidelines and produce a practical document, based on evidence, that could be used in everyday practice. The group created four consensus statements that would serve as a basis for their recommendations. One primary strategy used was to have chemotherapy-induced nausea and vomiting viewed as a single process that can occur throughout a treatment cycle, and not so much as an acute and a delayed process, as is usual in clinical trials. Patients' management should be considered over a 4- to 5-day period, rather than primarily dealing with the day of treatment only. The group created three tables: emetic risk of chemotherapy; treatment options based on emetic category; and antiemetic dosing recommendations. Use of these tables should make appropriate antiemetic selection more straightforward and easier for the practitioner in an everyday setting. Although this document alone may not solve all the challenges with appropriate antiemetic management, it will hopefully prove to be a step in the right direction.

Antiemetics↗

Chronic gastric electrical stimulation for gastroparesis reduces the use of prokinetic and/or antiemetic medications and the need for hospitalizations.

To investigate the effect of chronic gastric electrical stimulation (GES) on the daily use of prokinetics and antiemetics, hospitalizations, total symptom score (TSS), SF-36 status for health-related quality of life (HQOL), and gastric emptying of a solid meal, we evaluated 37 gastroparetic patients preoperatively and 1 year after undergoing GES implant. Prokinetic and antiemetic use was significantly reduced. Of 27 patients on at least one prokinetic at baseline, 8 were off at 1 year. Twenty-six patients requiring antiemetics before surgery decreased to 17. Mean TSS was significantly reduced and the reduction for patients off medications was significantly better than for patients still on medications. Overall SF-36 scores for HQOL were significantly improved, and patients off antiemetics had a significantly higher HQOL score than for patients on antiemetics at 1 year. Hospitalizations decreased from 50 +/- 10 days for the year prior to GES therapy to 14 +/- 3 days (P < 0.05). However, gastric emptying was not significantly improved. Conclusions are as follows. (1) Chronic GES significantly reduced the use of prokinetic/antiemetic medications and the need for hospitalization in gastropraretic patients, whose clinical and quality of life outcomes also significantly improved. (2) These data provide evidence of the positive economic impact of this new therapy on long-term clinical outcomes in gastroparetic patients not responding to standard medical therapy.

Adult↗

Blockade of lithium chloride-induced conditioned place aversion as a test for antiemetic agents: comparison of metoclopramide with combined extracts of Zingiber officinale and Ginkgo biloba.

The present study tests the hypothesis that the blockade of lithium chloride-induced conditioned place aversion might be a suitable model to assess antiemetic properties of drugs, especially in species that do not vomit, like rats. The effects of the known antiemetic compound metoclopramide were compared with those of zingicomb, a combination preparation of extracts of Ginkgo biloba and Zingiber officinale, also presumed to have antiemetic properties. Place conditioning was performed using a conventional three-compartment test procedure. On three successive conditioning trials, rats received an intraperitoneal (i.p.) injection of lithium chloride (125 mg/kg) and were placed into the compartment that they had preferred over three baseline trials. During the test, rats treated with lithium chloride (LiCl) spent less time in the treatment compartment, indicative of a conditioned place aversion (CPA). In the first experiment, metoclopramide (MCP) was administered intragastrically (IG) in doses of 2 or 10 mg/kg 60 min prior to LiCl injection. The pretreatment with 50 and 100 mg/kg zingicomb attenuated the LiCl-produced CPA, whereas a dosage of 10 mg/kg had no effect. These findings suggest that LiCl-induced CPA is a viable procedure with which to assess the antiemetic properties of metoclopramide. Furthermore, the data confirm the hypothesis that the phytopharmacon zingicomb might have antiemetic properties that are comparable to those of metoclopramide.

Animals↗

Comparative activity of antiemetic drugs.

Nausea and vomiting continues to be an important problem for cancer patients receiving chemotherapy. Chemotherapy-induced nausea and vomiting (CINV) are classified as acute, occurring within the first 24h, or delayed, occurring after the first 24h. A number of antiemetic agents are available for the management of nausea and vomiting, including 5-HT3-receptor-antagonists, corticosteroids, NK-1-receptor-antagonists, dopamine-receptor antagonists, benzodiazepines, neuroleptics and cannabinoids. With modern antiemetic therapy, vomiting can be prevented in 70-80% of patients, whereas the control of nausea remains suboptimal. The development of acute emesis is known to depend on serotonin. The pathophysiology of delayed emesis is less well understood, and multiple mechanisms may contribute, including substance P. Here, the most recent developments in the antiemetic therapy, including new antiemetic drugs and the latest guidelines for antiemetic prophylaxis, are reviewed.

Antiemetics↗

Antiemetic effects of granisetron, droperidol and dexamethasone in otologic surgery.

The objective was to assess the antiemetic activity of granisetron, dexamethasone and droperidol in the otologic surgeries. Sixty patients in ASA (American Society of Anesthesiologists) I and II risk groups who underwent surgery for chronic otitis media were assessed in a double blind and randomized trial. The patients were divided into three equal groups. Single intravenous dose of granisetron (3 mg), granisetron (3 mg) plus dexamethasone (8 mg) and droperidol (1.25 mg) were prophylactically administered to the patients in group 1, group 2 and group 3, respectively, and their antiemetic actions were compared. The antiemetic effects of the drugs were not significantly different between the groups (P>0.05). The antiemetic effects also did not differ significantly in the early and late postoperative periods (P>0.05). In conclusion, the results of prophylactic use or side effects of granisetron, granisetron plus dexamethasone or droperidol are similar in middle ear surgery. Therefore, cost effectivity of the antiemetic prophylaxis should be reconsidered in otologic surgery in the light of the results of this study.

Adult↗

The antiemetic effect of granisetron in lower hemibody radiotherapy.

Radiotherapy-induced emesis is poorly controlled with existing antiemetics. 5-Hydroxytryptamine (5HT3) receptor antagonists are a new class of antiemetics which have been demonstrated to be effective in controlling cytotoxic-induced emesis. We have prospectively studied the antiemetic efficacy of the 5HT3 receptor antagonist granisetron in an open non-randomized efficacy and toxicity study, at two dose levels, in patients receiving lower hemibody radiotherapy for multiple bone metastases. Of the 22 patients studied, 13 patients received 20 micrograms/kg and nine patients 40 micrograms/kg of granisetron, administered as an intravenous infusion 1 h before radiotherapy. Radiotherapy was administered as a single exposure to the lower half body to a midline dose of 8 Gy. A complete response (no nausea or vomiting) was observed in 9/13 patients at the lower dose level and 6/9 patients at the higher level. No major adverse events were recorded. We conclude that granisetron is a well-tolerated and effective antiemetic agent in radiotherapy-induced emesis. Formal comparison with conventional antiemetic agents in this situation is required.

Aged↗

Individualized outcome feedback produces voluntary antiemetic prescribing practice changes.

STUDY OBJECTIVE: To determine the impact of individualized outcome feedback on antiemetic prescribing practices and compare outcomes of a cost-effective, standardized antiemetic protocol (PROT) to that of customized antiemetic therapy (NONPROT). DESIGN: Prospective, observational study with randomized component. SETTING: Postanesthesia care unit (PACU) of an academic medical center. PATIENTS: 3027 consecutive ASA physical status I, II, and III patients receiving general anesthesia. INTERVENTIONS: Patients were randomized to receive 0.625 mg droperidol or 4 mg ondansetron for postoperative nausea and/or vomiting (PONV) from a protocol, or received customized antiemetic therapy. MEASUREMENTS AND MAIN RESULTS: Incidence of PACU PONV, selection of PROT versus NONPROT, patient satisfaction, and use of PONV prophylaxis were measured and indexed by an attending anesthesiologist in a monthly report for 4 months. Monthly expenditures for antiemetic therapy prior to, during, and after the study were collected. Literature on PONV outcomes, appropriate timing, and selection of PONV prophylaxis was distributed. The NONPROT group was slightly older than the PROT group; otherwise, demographics were similar between all groups. The incidence of PONV did not differ between the PROT and NONPROT groups (11% vs. 10%), and the incidence of PONV in patients receiving prophylaxis was higher in both groups (17% PROT vs. 15% NONPROT). Patients receiving ondansetron as a first-line drug required rescue therapy less often (5%) than those receiving droperidol (14%); however, patient satisfaction was indistinguishable among all groups. During the study, the use of prophylaxis decreased 47% without an increase in PONV, and PROT selection increased 54%. CONCLUSIONS: Individualized outcome feedback produced a 48% reduction in monthly expenditures for ondansetron and droperidol, which was sustained after the study. Patients satisfaction between ondansetron 4 mg and droperidol 0.625 mg given in the PACU did not differ in spite of a slightly greater efficacy of ondansetron as a first-line drug.

Adult↗

An analysis of the antiemetic protection of metoclopramide plus dexamethasone in Chinese patients receiving moderately high emetogenic chemotherapy.

This descriptive study aimed to evaluate the antiemetic protection of metoclopramide plus dexamethasone in a sample of 33 Chinese breast cancer patients who were receiving doxorubicin and cyclophosphamide. The antiemetic protection effect was not satisfactory. The results showed that the worst nausea and vomiting was experienced on the third day, with 87.9% of patients reporting nausea and 63.6% experiencing vomiting on that day. In almost one-third of the sample antiemetic medication failed to protect against either acute vomiting or delayed vomiting (i.e. patients continued to experience more than five emetic episodes). Complete protection from acute vomiting was seen in 36.4% of patients, whereas complete protection from delayed vomiting was seen in only one-third of the patients. There was an association between acute nausea/vomiting and delayed nausea/vomiting. Different types of antiemetics need to be offered to Chinese patients receiving chemotherapy (i.e. 5-HT3 receptor antagonists or a combination of antiemetics), but more research should be directed to this area.

Adult↗