tropisetron and Vomiting

To compare the efficacy of prophylactic ondansetron and tropisetron for postoperative nausea and vomiting (PONV).. A literature search was performed to identify studies that compare the efficiency of ondansetron with that of tropisetron in preventing PONV. Only randomized controlled trials updated to January, 2021 were included.. The final pooled analysis included 14 studies totaling 1705 patients and indicated that ondansetron was 39% less effective than tropisetron in preventing postoperative vomiting with a higher incidence of dizziness. However, no significant difference was detected between ondansetron and tropisetron in PONV, postoperative nausea, antiemetic treatment, and headache.. Tropisetron is superior to ondansetron in preventing postoperative vomiting.PROSPERO No: CRD42021237368.

Topics: Antiemetics; Double-Blind Method; Humans; Ondansetron; Postoperative Nausea and Vomiting; Randomized Controlled Trials as Topic; Tropisetron; Vomiting

Review the clinical evidence of tropisetron or palonosetron, an old- and new-generation serotonin (5-hydroxytryptamine) type 3 (5-HT3) receptor antagonist (RA), respectively, for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with cancer, and evaluate any difference in efficacy trends. A literature search of the EMBASE and PubMed databases was performed to identify publications of intravenous (IV) tropisetron (generic forms or Navoban®) for the treatment of CINV in patients with various cancers. Data from the pivotal clinical studies evaluating the IV formulation of Aloxi® (palonosetron HCl) were also considered. The effectiveness and safety of each antiemetic was summarized. Sixteen papers for tropisetron fulfilled the inclusion criteria and were extracted for full analysis; publications from six pivotal palonosetron clinical trials were considered. No direct data comparisons could be made between the two drugs, due to the varying definitions of efficacy endpoints between studies. For tropisetron, the rates of no emesis were lower in patients receiving highly emetogenic chemotherapy (HEC) versus moderately emetogenic chemotherapy (MEC). For palonosetron, the rates of complete response (no emesis, no rescue medication) were comparable in the MEC and HEC settings, demonstrating the effectiveness of this agent in patients receiving HEC. Both antiemetics offered some protection against nausea, although lower rates of no nausea were achieved compared with rates of no emesis. Two trials that evaluated the efficacy of palonosetron and tropisetron within the same study reported that palonosetron was more effective than tropisetron in controlling delayed vomiting in the HEC and MEC settings, with significantly higher rates of no emesis observed (P≤0.01). Palonosetron was non-inferior or more efficacious in controlling CINV compared with other older 5-HT3RAs, such as dolasetron, ondansetron, and granisetron. Conversely, tropisetron was no more efficacious than ondansetron or granisetron. Both tropisetron and palonosetron were generally well tolerated, with adverse event profiles consistent with drugs of this class (e.g., headache, constipation, and diarrhea). These data suggest that palonosetron is a highly selective prophylactic agent that may have an improved therapeutic profile compared with tropisetron, and is a feasible treatment option for controlling CINV in patients with cancer.

Topics: Antineoplastic Agents; Female; Humans; Male; Nausea; Neoplasms; Palonosetron; Tropisetron; Vomiting

Nausea is a common symptom in advanced cancer, with a prevalence of up to 70%. While nausea and vomiting can be related to cancer treatments, such as chemotherapy, radiotherapy, or surgery, a significant number of people with advanced cancer also suffer from nausea unrelated to such therapies. Nausea and vomiting may also cause psychological distress, and have a negative impact on the quality of life of cancer patients; similarly to pain, nausea is often under-treated. The exact mechanism of action of corticosteroids on nausea is unclear, however, they are used to manage a number of cancer-specific complications, including spinal cord compression, raised intracranial pressure, and lymphangitis carcinomatosis. They are also commonly used in palliative care for a wide variety of non-specific indications, such as pain, nausea, anorexia, fatigue, and low mood. However, there is little objective evidence of their efficacy in symptom control, and corticosteroids have a wide range of adverse effects that are dose and time dependent. In view of their widespread use, it is important to seek evidence of their effects on nausea and vomiting not related to cancer treatment.. To assess the effects of corticosteroids on nausea and vomiting not related to chemotherapy, radiotherapy, or surgery in adult cancer patients.. We searched CENTRAL, MEDLINE Ovid, Embase Ovid, CINAHL EBSCO, Science Citation Index Web of Science, Latin America and Caribbean Health Sciences (LILACS), Conference Proceedings Citation Index - Science Web of Science, and clinical trial registries, from inception to 23rd August 2016.. Any double-blind randomised or prospective controlled trial that included adults aged 18 years and over with advanced cancer with nausea and vomiting not related to chemotherapy, radiotherapy, or surgery were eligible for the review, when using corticosteroids as antiemetic treatment.. All review authors independently assessed trial quality and extracted data. We used arithmetic means and standard deviations for each outcome to report the mean difference (MD) with 95% confidence interval (CI). We assessed the quality of the evidence using GRADE and created a 'Summary of findings' table.. Three studies met the inclusion criteria, enrolling 451 participants. The trial size varied from 51 to 280 participants. Two studies compared dexamethasone to placebo, and the third study compared a number of additional interventions in various combinations, including metoclopramide, chlorpromazine, tropisetron, and dexamethasone. The duration of the studies ranged from seven to 14 days. We included two studies (127 participants) with data at eight days in the meta-analysis for nausea intensity; no data were available that incorporated the same outcome measures for the third study. Corticosteroid therapy with dexamethasone resulted in less nausea (measured on a scale of 0 to 10, with a lower score indicating less nausea) compared to placebo at eight days (MD 0.48 lower nausea, 95% CI 1.53 lower to 0.57 higher; very low-quality evidence), although this result was not statistically significant (P = 0.37). Frequency of adverse events was not significantly different between groups, and the interventions were well tolerated. Factors limiting statistical analysis included the lack of standardised measurements of nausea, and the use of different agents, dosages, and comparisons. Subgroup analysis according to type of cancer was not possible due to insufficient data. The quality of this evidence was downgraded by three levels, from high to very low due to imprecision, likely selection bias, attrition bias, and the small number of participants in the included studies.. There are few studies assessing the effects of corticosteroids on nausea and vomiting not related to chemotherapy, radiotherapy, or surgery in adult cancer patients. This review found very low-quality evidence which neither supported nor refuted corticosteroid use in this setting. Further high quality studies are needed to determine if corticosteroids are efficacious in this setting.

Topics: Adrenal Cortex Hormones; Adult; Chlorpromazine; Dexamethasone; Humans; Indoles; Metoclopramide; Nausea; Neoplasms; Time Factors; Tropisetron; Vomiting

5-HT3 receptor antagonists are extensively used as efficacious agents in counteracting chemotherapy-induced emesis. Recent investigations have shed light on other potential effects (analgesic, anxiolytic, and anti-psychotic). Some studies have reported neuroprotective properties for the 5-HT3 receptor antagonists in vitro and in vivo. When administered to Aβ-challenged rat cortical neurons, 5-HT3 receptor antagonists substantially abated apoptosis, elevation of cytosolic Ca(2), glutamate release, reactive oxygen species (ROS) generation, and caspase-3 activity. In addition, in vivo studies show that 5-HT3 receptor antagonists possess, alongside their anti-emetic effects, notable immunomodulatory properties in CNS. We found that pretreatment with tropisetron significantly improved neurological deficits and diminished leukocyte transmigration into the brain, TNF-α level, and brain infarction in a murine model of embolic stroke. Our recent investigation revealed that tropisetron protects against Aβ-induced neurotoxicity in vivo through both 5-HT3 receptor-dependent and -independent pathways. Tropisetron, in vitro, was found to be an efficacious inhibitor of the signaling pathway leading to the activation of pro-inflammatory NF-κB, a transcription factor pivotal to the upregulation of several neuroinflammatory mediators in brain. This mini review summarizes novel evidence concerning effects of 5-HT3 antagonists and their possible mechanisms of action in ameliorating neurodegenerative diseases including Alzheimer, multiple sclerosis, and stroke. Further, we discuss some newly synthesized 5-HT3 receptor antagonists with dual properties of 5-HT3 receptor blockade/alpha-7 nicotinic receptor activator and their potential in management of memory impairment. Since 5-HT3 receptor antagonists possess a large therapeutic window, they can constitute a scaffold for design and synthesis of new neuroprotective medications.

Topics: Animals; Drug Therapy; Humans; Indoles; Multiple Sclerosis; Receptors, Serotonin, 5-HT3; Serotonin 5-HT3 Receptor Antagonists; Tropisetron; Vomiting

Double-blinded, randomized, placebo-control trials of selective serotonin 3 receptor antagonists (5-HT3R-ANTs) for schizophrenia have differed in outcome. This meta-analysis tests the hypothesis that 5-HT3R-ANTs are effective for the treatment for schizophrenia. We searched PubMed, the Cochrane Library database, and PsycINFO up to June 15, 2013. We conducted a systematic review and meta-analysis of individual patient data from randomized controlled trials comparing 5-HT3R-ANTs add-on therapy with placebo. The risk ratio (RR), 95 % confidence intervals (CI), and standardized mean difference (SMD) were calculated. A random-effects model was used. Six studies (total n = 311) were identified. These included one granisetron plus risperidone study, one ondansetron plus risperidone study, one ondansetron plus haloperidol, and three tropisetron plus risperidone studies. The statistically significant effects of 5-HT3R-ANTs add-on therapy on Positive and Negative Syndrome Scale (PANSS) total scores were SMD = -1.03, CI = -1.70 to -0.36, p = 0.003 (I (2) = 82 %, 5 studies, n = 261); on negative scores were SMD = -1.10, CI = -1.82 to -0.39, p = 0.002 (I (2) = 84 %, 5 studies, n = 261); and on PANSS general scores were SMD = -0.70, CI = -1.23 to -0.17, p = 0.01 (I (2) = 73 %, 5 studies, n = 261). However, 5-HT3R-ANTs add-on therapy was not superior to placebo in PANSS positive scores (SMD = -0.12, p = 0.33). Dropout due to all cause (RR = 0.80, p = 0.50), inefficacy (RR = 0.76, p = 0.65), or adverse events (RR = 0.84, p = 0.75) was similar in both groups. Constipation occurred significantly more often with 5-HT3R-ANTs than placebo (RR = 2.05, CI = 1.07-3.91, p = 0.03, NNH = 11, p = 0.02). 5-HT3R-ANTs add-on therapy is more beneficial on the psychopathology (especially negative symptoms) than controls in patients with schizophrenia, and 5-HT3R-ANTs seem to be well-tolerated treatments.

Topics: Antipsychotic Agents; Constipation; Double-Blind Method; Drug Therapy, Combination; Granisetron; Haloperidol; Humans; Indoles; Nausea; Ondansetron; Randomized Controlled Trials as Topic; Receptors, Serotonin, 5-HT3; Risperidone; Schizophrenia; Serotonin 5-HT3 Receptor Antagonists; Severity of Illness Index; Symptom Assessment; Treatment Outcome; Tropisetron; Vomiting

Comparing antiemetic efficacy of different 5-HT(3)-receptor antagonists (5-HT(3)RAs) is difficult due to inter-study variability. Therefore, a meta-analysis was performed to comparatively evaluate dolasetron, granisetron, ondansetron and tropisetron for acute chemotherapy-induced nausea and vomiting (CINV).. Comparisons between 5-HT(3)RAs were based on 44 randomized studies (including 12,343 patients) identified by MEDLINE, CANCERLIT or EMBASE searches and subcategorized by chemotherapy type (cisplatin- or non-cisplatin-based).. When all studies were combined, granisetron was equivalent to ondansetron (n = 27), and showed an advantage vs tropisetron (p = 0.018; n = 12). Ondansetron vs tropisetron (n = 11) and ondansetron vs dolasetron (n = 3) revealed equivalence in each comparison. An advantage for 3 mg granisetron vs 8 mg ondansetron was found in non-cisplatin-based studies (p = 0.015; n = 6). Overall equivalence was seen between ondansetron, 24 or 32 mg, and granisetron, 2 or 3 mg, for all studies (n = 13). There was a possible advantage for higher (24 or 32 mg) vs lower (8 mg) ondansetron dose regimens with cisplatin-based trials (n = 6). No differences were seen between 3 and 1 mg granisetron doses (n = 6).. Efficacy of 5-HT(3)RAs for preventing CINV following cisplatin- and non-cisplatin-based chemotherapy is comparable, with the exception of granisetron vs tropisetron. Some differences were noted in dosing subanalyses.

Topics: Antiemetics; Antineoplastic Agents; Granisetron; Humans; Indoles; Ondansetron; Quinolizines; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Treatment Outcome; Tropisetron; Vomiting

This analysis compares the antiemetic efficacy of the 5-HT3-receptor antagonists granisetron and tropisetron in acute chemotherapy-induced nausea and vomiting (CINV). All published randomized studies comparing granisetron with tropisetron in conventionally-dosed, emetogenic chemotherapy are included in this pooled analysis. The target criterion for antiemetic success was 'acute complete response' (complete absence of vomiting in the 24 h after the start of chemotherapy) and the rate of successful treatment reported as 'response rate' (acute complete response rate per patient). Twelve studies were used comprising 810 patients. Comparison between granisetron and tropisetron in patients receiving cisplatin-based therapy showed superiority of granisetron (odds ratio above 1.0) in six out of seven studies. However, this difference did not reach statistical significance. In patients receiving noncisplatin-based therapies, four out of five studies showed an advantage of granisetron over tropisetron with one study showing a significant advantage. Pooled analysis of all studies demonstrated a significant overall advantage for granisetron over tropisetron (p=0.042). This is supported by the individual studies: overall, ten out of the 12 studies analyzed showed an advantage for granisetron, with a 6.4% difference in response rate. This advantage was more pronounced in noncisplatin-based therapy (7.3%), whereas in cisplatin-based therapy, the difference was 5.4%. The overall results of this pooled analysis of cisplatin and noncisplatin-based studies suggest that granisetron has a marginal but clinically potentially relevant statistically significant advantage in efficacy over tropisetron for the control of acute CINV.

Topics: Antiemetics; Antineoplastic Agents; Granisetron; Humans; Indoles; Serotonin Antagonists; Tropisetron; Vomiting

The antiemetic efficacy and tolerability of Tropisetron (Navoban, Novartis Pharma Switzerland AG, Bern), a selective 5-hydroxytriptamine receptor antagonist, has been assessed in the prevention of acute vomiting in children receiving chemotherapy for solid tumors. Tropisetron iv was given 30 min before administration of chemotherapy at a dose of 5 mg in children <20 kg body weight and at a dose of 10 mg in those >20 kg. A total of 50 children were studied in 189 courses of chemotherapy. Control of emesis was defined as total in absence of acute vomiting, as major if 1 or 2 events of acute vomiting occurred, and as not controlled if >2 events of acute vomiting occurred. Response was studied, taking into account Tropisetron dosage, degree of emetogenicity of the chemotherapeutic agents in pretreated and non-pretreated patients, and according to age groups. Tropisetron, administered in a single daily dose of 8-12 mg/m(2), was found to be very effective in completely controlling acute emesis in 92% of the courses of moderately and highly emetogenic chemotherapy administered to pediatric patients with solid tumors. Moreover, Tropisetron, at this dosage, did not lead to any adverse effects.

Topics: Adolescent; Adult; Age Factors; Analysis of Variance; Antiemetics; Antineoplastic Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Humans; Indoles; Infant; Infusions, Intravenous; Male; Tropisetron; Vomiting

The need to control chemotherapy-induced emesis has stimulated research into anti-emetics. Emesis is not only unpleasant, but negatively impacts on global quality of life. The development of two new classes of drugs has been responsible for the major advances in anti-emesis. The 5 hydroxytryptamine3 (5HT3) antagonists in combination with dexamethasone significantly improved the control of acute post chemotherapy emesis, but delayed emesis which can last for several days was still problematic, yet its incidence was underestimated by clinicians. Both the control of acute and delayed emesis was improved when the neurokinin1 (NK1) receptor antagonists were added to 5HT3 antagonists and steroids. The complete control of delayed emesis was improved by 21% with little toxicity. The triple drug combination has become the standard of care for preventing the emesis associated with cytotoxic drugs of high emetic potential.

Topics: Administration, Oral; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Australia; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Granisetron; Humans; Indoles; Isoquinolines; Male; Neoplasms; Ondansetron; Palonosetron; Patient Satisfaction; Prognosis; Quality of Life; Quinolizines; Quinuclidines; Treatment Outcome; Tropisetron; Vomiting

Cytotoxic drug-induced nausea and vomiting are the side effects most feared by cancer patients. Emesis is an instinctive defense reaction caused by the somato-autonomic nerve reflex, which is integrated in the medulla oblongata. Emesis caused by anticancer drugs is associated with an increase in the concentration of serotonin (5-HT) (5-HT) in the intestinal mucosa and brainstem. 5-HT released from the enterochromaffin (EC) cells, which synthesize and secrete 5-HT, stimulates the 5-HT receptors on the adjacent vagal afferent nerves. The depolarization of the vagal afferent nerves stimulates the vomiting center in the brainstem and eventually induces a vomiting reflex. 5-HT released from EC cells appears to mediate the cisplatin-induced emesis sensitive to 5-HT(3) receptor antagonists. The precise role of 5-HT in the occurrence of vomiting has not been fully elucidated. The present review describes the role of 5-HT in anticancer drug-induced emesis from the viewpoint of 5-HT release and afferent vagal nerve activity. Various models and methods for predicting emesis are also evaluated.

Topics: Animals; Antiemetics; Antineoplastic Agents; Cisplatin; Enterochromaffin Cells; Granisetron; Humans; Indoles; Ondansetron; Receptors, Serotonin, 5-HT3; Receptors, Serotonin, 5-HT4; Serotonin; Serotonin 5-HT3 Receptor Antagonists; Serotonin 5-HT4 Receptor Antagonists; Serotonin Antagonists; Tropisetron; Vagus Nerve; Vomiting

Tropisetron is a serotonin (5-hydroxytryptamine; 5-HT) antagonist that is primarily used in the prevention of chemotherapy-induced nausea and vomiting. Antagonism of 5-HT3 binding sites in the peripheral and central nervous system is the probable mechanism of prevention of acute nausea and vomiting. Effects on delayed nausea and vomiting are less well understood as these are probably not mediated solely by 5-HT3 receptors. Tropisetron monotherapy is effective for the control of acute, and to a lesser extent delayed, nausea and vomiting in patients receiving moderately to severely emetogenic chemotherapy. The combination of dexamethasone and tropisetron is more effective than monotherapy. Complete control of cisplatin-induced nausea and vomiting was obtained in 69 to 97% of patients receiving the combination compared with 46 to 80% receiving tropisetron monotherapy in randomised trials. There were generally no significant differences between the control of acute or delayed nausea and vomiting provided by tropisetron, ondansetron or granisetron in randomised, comparative trials. The antiemetic efficacy of tropisetron was maintained over multiple cycles of chemotherapy. Most comparative studies showed tropisetron monotherapy to be more effective than metoclopramide in controlling acute nausea and vomiting, with the exception of 1 study which showed similar efficacy. However, high dose metoclopramide plus dexamethasone provided similar control of delayed emesis to tropisetron plus dexamethasone. Tropisetron is also effective in children, including those who responded poorly to previous antiemetic treatment. Tropisetron and ondansetron generally have similar efficacies in this population. The drug enhanced patients' quality of life and was well tolerated by adults and children alike. The recommended oral and IV dosage of tropisetron is 5 mg once daily; there is no increase in efficacy with doses >5 mg.. Tropisetron is similar to other 5-HT3 receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting in both adults and children. It is suitable as first-line therapy (combined with a corticosteroid) for the prevention of acute nausea and vomiting in patients treated with moderately to severely emetogenic chemotherapeutic agents. This combination is also moderately effective in the prevention of delayed nausea and vomiting.

Topics: Animals; Antiemetics; Antineoplastic Agents; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Indoles; Nausea; Quality of Life; Serotonin Antagonists; Tropisetron; Vomiting

Tropisetron is used as an anti-emetic agent against chemotherapy-induced nausea and vomiting. Tropisetron shows strong 5-HT3 antagonist and weak 5-HT4 antagonist activities in vitro. In the various animal models of vomiting including chemotherapy- or radiotherapy-induced emesis in the dog and ferret, tropisetron is reported to inhibit the emetic episodes. The potent anti-emetic activity of oral tropisetron rather than the i.p. administered drug suggests that it can act directly from the intestinal lumen as well as from the blood stream after its absorption. Moreover, the anti-emetic activity of tropisetron may involve the 5-HT4-receptor mechanism in addition to the 5-HT3-receptor mechanism. Tropisetron has several pharmacological activities other than anti-emesis such as the stimulation of the gastric emptying and the inhibition of the diarrhea, visceral pain and anxiety. These effects of tropisetron may contribute to the high clinical efficacy of tropisetron against chemotherapy-induced emesis.

Topics: Administration, Oral; Animals; Antiemetics; Antineoplastic Agents; Anxiety; Diarrhea; Disease Models, Animal; Dogs; Gastric Emptying; In Vitro Techniques; Indoles; Nausea; Radiotherapy; Receptors, Serotonin; Serotonin Antagonists; Tropisetron; Vomiting

The knowledge of the importance, the physiopathological mechanisms, and the management of the chemotherapy-induced emesis has increased exponentially during the last 20 years. High-dosage metoclopramide (MCP) therapy has been introduced in the eighties and serotonine type-3 receptor antagonists (5-HT(3) antagonists) have been used since the late eighties and early nineties. Due to both classes of substances the results of the antiemetic therapies have improved drastically. After 20 years of intensive clinical research it seems to be appropriate to come to an intermediate conclusion.. With the aid of an overview and a new analysis of the literature published on this topic so far, the current state of research is shown (including the fields in which further improvement will be necessary), and suggestions are made, wherever it seemed possible, to attain the "gold standard" in antiemetic therapy.. In connection with all highly or very highly emetogenic chemotherapies, an antiemetic prophylaxis should be initiated on the day of therapy, especially when using platinum or most of the cyclophosphamide-based regimes for cancer treatment. The recommended prophylaxis consists of a combination of 5-HT(3) antagonists with a corticosteroid. To combat the so-called delayed emesis on the days following therapy, all patients should undergo an oral corticoid therapy, possibly in combination with MCP (especially platinum-therapy patients), less frequently with 5-HT(3) antagonists. With these means of prophylaxis emesis can be prevented/avoided completely in most patients, and nausea can at least be reduced. It is sufficient to administer a single dose of 5-HT(3) antagonists prior to chemotherapy. For ondansetron and granisetron, the best documented substances within this class of drugs, 8 mg (ondansteron) and 3 mg (granisetron) are considered standard dosages. Among the corticoids, most data have been accumulated for dexamethasone. A standard dose of 10 to 20 mg can be administered prior to chemotherapy. Right after and especially on the days following chemotherapy higher dosages seem to be indicated.. Further therapy improvements, especially concerning emesis and nausea on the days following chemotherapy, are necessary and are currently object of clinical research.

Topics: Antineoplastic Combined Chemotherapy Protocols; Benchmarking; Dexamethasone; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Granisetron; Humans; Indoles; Metoclopramide; Nausea; Ondansetron; Premedication; Randomized Controlled Trials as Topic; Research; Serotonin 5-HT3 Receptor Antagonists; Tropisetron; Vomiting

In the past few years important progress in the prevention of chemotherapy-induced nausea and vomiting has been made mainly thanks to the introduction of the 5-HT3 receptor antagonists in clinical practice (ondansetron, granisetron, tropisetron). In the prevention of acute emesis induced by cisplatin, an intravenous combination of a 5-HT3 receptor antagonist plus single dose dexamethasone (20 mg) should be considered the treatment of choice. This is also the case in the prevention of acute emesis induced by moderately emetogenic chemotherapy (intravenous cyclophosphamide, doxorubicin, epirubicin, carboplatin, used alone or in combination), but high and repeated doses of dexamethasone should be used (8 mg intravenously plus 4 mg orally every 6 hours for four doses starting contemporarily to chemotherapy administration). Several-well conducted double-blind comparative studies among intravenously administered 5-HT3 receptor antagonists have been carried out. Almost all showed that they have identical antiemetic activity and tolerability. Therefore, the choice among 5-HT3 receptor antagonists should be based only on their acquisition cost in each country. In the prevention of delayed emesis (from day 2 to day 4) induced by cisplatin oral metoclopramide (0.5 mg/kg or 20 mg every 6 hours for four doses daily) and oral ondansetron (8 mg twice daily), both combined with dexamethasone, showed similar antiemetic efficacy. Metoclopramide plus dexamethasone should be considered the antiemetic regimen of choice due to its lower cost. Ondansetron plus dexamethasone is a valid alternative regimen that should be preferred in patients who not tolerate metoclopramide and in patients who suffer from acute vomiting. In the prevention of delayed emesis induced by moderately emetogenic chemotherapy oral dexamethasone or oral ondansetron showed a good antiemetic efficacy, but the results from a recently published study seem suggest the necessity to treat only patients who present acute vomiting or moderate-severe nausea. In fact, patients obtaining complete protection from vomiting and nausea (or at most mild acute nausea) have a very low incidence of delayed emesis.

Topics: Antiemetics; Antineoplastic Agents; Cisplatin; Dexamethasone; Drug Therapy, Combination; Granisetron; Humans; Indoles; Metoclopramide; Nausea; Ondansetron; Phenothiazines; Serotonin Antagonists; Tropisetron; Vomiting

Topics: Anesthesia, General; Antiemetics; Double-Blind Method; Humans; Indoles; Multicenter Studies as Topic; Nausea; Postoperative Complications; Randomized Controlled Trials as Topic; Serotonin Antagonists; Treatment Outcome; Tropisetron; Vomiting

Since there continues to be a high incidence of postoperative nausea and vomiting associated with many types of surgery, and the standard antiemetics often do not achieve satisfactory results, there have been attempts to use the 5-HT3 antagonists. This group of substances is relatively new, but has already been used successfully as an antiemetic during chemotherapy. To date, results are on hand for four different 5-HT3 receptor blockers: ondansetron, tropisetron, granisetron and dolasetron. Applied intravenously, all four have been effective both in prophylaxis and also as therapy for postoperative emesis. Except for ondansetron, there is so far no definitely clear knowledge about the lowest possible effective dosage. The entire group is well tolerated: only occasional and minor side effects have been reported. Even though not all the hopes originally set in the 5-HT3 group of antagonists have been fulfilled, progress has nevertheless been achieved. Especially noteworthy points are a positive cost-effectiveness relationship of these drugs and their appropriate use in case of the proper indications.

Topics: Antiemetics; Clinical Trials as Topic; Dose-Response Relationship, Drug; Granisetron; Humans; Indoles; Infusions, Intravenous; Nausea; Ondansetron; Postoperative Complications; Quinolizines; Serotonin Antagonists; Tropisetron; Vomiting

This analysis was undertaken to review published reports of the comparative efficacy and safety of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists in the prophylaxis of acute chemotherapy-induced emesis.. Comparison data used are the preclinical pharmacology as well as the design and results of clinical trials. Seven comparative studies that used granisetron, ondansetron, or tropisetron in patients who received either moderately or highly emetogenic chemotherapy are reviewed. As the study designs, patient population, chemotherapy, antiemetic doses and schedule, and methods of assessment were slightly different, the results of each study are analyzed independently. Effectiveness is assessed by emetic episodes, nausea, and patient preference.. The preclinical pharmacologic profile is different among the 5-HT3 antagonists in terms of potency, selectivity, dose response, and duration of action. The comparative clinical trials show that a single intravenous (i.v.) dose of granisetron 3 mg is as effective as multiple (8 mg x 3) or single (32 mg) i.v. doses of ondansetron for the prevention of acute nausea and emesis due to cisplatin. In the two moderately emetogenic clinical trials, granisetron 3 mg i.v. was at least as effective as ondansetron 8 mg i.v. +/- 24 mg orally and tropisetron 5 mg i.v. Patient preference was evaluated in three of the four crossover trials: granisetron was preferred in three of four, and no preference was reported in the fourth. The one trial to compare ondansetron 0.15 mg/kg x 3 versus granisetron 10 micrograms/kg x 1 or granisetron 40 micrograms/kg i.v. demonstrated equivalent control of nausea and vomiting in patients who received cisplatin-based chemotherapy.. The 5-HT3 receptor antagonists compared are highly effective antiemetic agents that have now become the standard of care for preventing chemotherapy-induced emesis. Whether the described preclinical differences among these agents are also clinically significant remains to be seen. In the comparative trials analyzed, the 5-HT3 receptor antagonists demonstrated relatively equivalent clinical efficacy. Cost analysis may favor the use of one agent over another depending on the emetogenic challenge, dose of the 5-HT3 antagonists, and number of doses recommended. Patient preference may be an important factor to be considered in future antiemetic trials.

Topics: Antiemetics; Antineoplastic Agents; Cisplatin; Granisetron; Humans; Indoles; Ondansetron; Prognosis; Selective Serotonin Reuptake Inhibitors; Tropisetron; Vomiting

Topics: Antiemetics; Evaluation Studies as Topic; Humans; Indoles; Ondansetron; Randomized Controlled Trials as Topic; Treatment Outcome; Tropisetron; Vomiting

Nausea and vomiting are the most distressing side effects associated with the administration of chemotherapy for neoplastic diseases. Nausea, in particular, often had been ignored in studies of chemotherapy side effects. Recently, progress has been made in the control of chemotherapy-induced nausea and vomiting, due, in part, to a better understanding of the physiologic mechanisms involved.. This paper reviews recent advances in the control of emesis, focusing on pharmacologic treatments.. The efficacy and safety of the serotonin (5-HT3) receptor antagonists granisetron, ondansetron, and tropisetron in the control of acute and delayed emesis and emesis induced by repeat-cycle chemotherapy are summarized. Although differences in study design and definitions of response criteria have made it difficult to compare the studies that have evaluated these three agents, the overall body of literature supports several clinical findings.. (1) The 5HT3 antiemetic agents have been shown to be clinically more effective in the control of nausea and emesis than previously used agents. (2) No one of the three has demonstrated consistently greater efficacy. (3) Efficacy appears to be more pronounced for cisplatin-containing regimens than for moderate or less emetogenic chemotherapy regimens. (4) Effectiveness of the 5HT3 agents appears to be less for delayed nausea and emesis than for acute symptoms. Potential control of anticipatory nausea and emesis has not been investigated. (5) Control over nausea appears to be significantly less than control over emesis. In the studies in which it has been measured, nausea control remains incomplete for approximately half the patients given 5HT3 agents. (6) The efficacy of the agents appears to diminish across repeated days and, perhaps, across repeated chemotherapy cycles. (7) The addition of a steroid such as dexamethasone increases the efficacy of both 5HT3 and other antiemetic agents. This effect also seems to apply to delayed nausea and emesis.

Topics: Antiemetics; Antineoplastic Agents; Granisetron; Humans; Indoles; Nausea; Ondansetron; Serotonin Antagonists; Tropisetron; Vomiting

The serotonin-receptor (5-HT3) antagonists combined with dexamethasone are considered the antiemetic therapy of choice in the prevention of cisplatin-induced emesis. As there are now several compounds on the market, the dilemma of preference is particularly relevant. In preclinical studies some differences among the three marketed drugs (ondansetron, granisetron and tropisetron) have emerged. In particular, tropisetron and granisetron have a greater potency and duration of action and seem to have a greater selectivity toward the 5-HT3 receptor with respect to ondansetron. Furthermore, while with tropisetron and granisetron there is a linear dose/response relationship, this does not seem to be the case for ondansetron. These preclinical differences, however, do not seem to correlate with the clinical antiemetic activity of these compounds. In fact, although the number of comparative studies is small, with all of them presenting several shortcomings (small number of patients, not blinded studies, no association with steroids, sponsored trials), it seems that the antiemetic activity and tolerability of ondansetron, granisetron and tropisetron is very similar. If these data are confirmed, the least expensive of the 5-HT3 antagonists should be the drug of choice. We feel, however, that the answer to this rather difficult question of choice will come from very large, independent, methodologically correct studies designed to show small but clinically significant differences (i.e., less than 10% in complete protection from emesis). These trials, which require about 1000-1500 patients, are ongoing and the one carried out as a multicenter study by the Italian Group for Antiemetic Research is close to conclusion.

Topics: Animals; Antiemetics; Cisplatin; Clinical Trials as Topic; Dose-Response Relationship, Drug; Granisetron; Humans; Indoles; Neoplasms; Ondansetron; Serotonin Antagonists; Tropisetron; Vomiting

Tropisetron is a potent and selective serotonin 3 (5-hydroxytryptamine3; 5-HT3) receptor antagonist with antiemetic properties, probably mediated via antagonism of receptors both at peripheral sites and in the central nervous system. When compared with antiemetic regimens containing high-dose metoclopramide in a small number of studies, tropisetron was generally as effective at preventing acute and delayed vomiting induced by high-dose cisplatin (> or = 50 mg/m2). In these studies tropisetron completely prevented vomiting occurring in the first 24 hours after chemotherapy in 35 to 76% of patients. Tropisetron was superior to alizapride in preventing emesis induced by high-dose alkylating agents. The effectiveness of tropisetron in patients who had previously had partial control of emesis was improved by the addition of dexamethasone. Tropisetron appears to be well tolerated with the most frequently reported adverse effect being headache. Extrapyramidal effects, which can occur in 5 to 10% of patients receiving high-dose metoclopramide and which may limit its use, have been reported in only isolated cases with tropisetron. Thus, tropisetron is an effective, apparently well tolerated agent which can be administered once daily for the prevention of chemotherapy-induced nausea and vomiting. However, further clinical experience is needed to clarify the optimum role of tropisetron as an antiemetic agent, particularly with regard to other drugs in its class. Nonetheless, preliminary results indicate that tropisetron will be a useful alternative for use in controlling emesis induced by cytotoxic therapy.

Topics: Animals; Antiemetics; Antineoplastic Agents; Clinical Trials as Topic; Humans; Indoles; Nausea; Neoplasms; Tropisetron; Vomiting

This review discusses the development of tropisetron as an antiemetic drug with the patient in mind. The original aims of the programme and the progress achieved towards them to date are described. The efficacy and safety data from two dose-ranging studies and four comparative-treatment studies with tropisetron were combined in a prospectively planned meta-analysis of 799 patients. An integrated safety summary is presented which includes all patients from the six studies. Tropisetron at a dose of 5 mg once daily is an effective and well-tolerated, single-agent, antiemetic treatment, which can be given without special precautions to all patients receiving highly emetogenic chemotherapy. In comparison with metoclopramide, tropisetron is more effective in the prevention of nausea and vomiting. When compared with the most potent cocktail treatments currently in use (containing high-dose metoclopramide, dexamethasone and lorazepam or diphenhydramine), tropisetron is equally effective in the prevention of acute vomiting and somewhat less effective in the prevention of nausea. Overall, tropisetron is an effective and well-tolerated antiemetic treatment that is simple to administer, comparing well with currently available antiemetic cocktails. Tropisetron remains effective for the prevention of nausea and vomiting during multiple chemotherapy courses. The simple dosing schedule (5 mg i.v. day 1; one 5 mg capsule daily, days 2-6) makes tropisetron ideal for both inpatient or outpatient use.

Topics: Antiemetics; Antineoplastic Agents; Humans; Indoles; Nausea; Serotonin Antagonists; Tropisetron; Vomiting

This state-of-the-art review describes the development, over the past 12 years, of new agents for the control of chemotherapy- and radiotherapy-induced emesis. While the mechanism of chemotherapy-induced nausea and vomiting is still not fully understood, significant progress in prevention of the symptoms has been achieved. The discovery that high-dose metoclopramide was very effective in antiemetic control ultimately led to the development of a new class of antiemetics, the 5-HT3 receptor antagonists, of which tropisetron is the most recent to be introduced. The emphasis of the review is on acute chemotherapy-induced emesis and includes current thinking on the influence of patient characteristics on the emetic outcome. The new 5-HT3 receptor antagonists do not demonstrate any of the distressing extrapyramidal reactions so frequently encountered with conventional antiemetics acting at dopamine receptor sites. Mild headache is the most characteristic side effect of this class of agents. The major advantages of the newer 5-HT3 receptor antagonists, such as tropisetron, over the conventional antiemetic regimens are convenience, flexibility and, above all, single-dose usage.

Topics: Antiemetics; Antineoplastic Agents; Drug-Related Side Effects and Adverse Reactions; Humans; Indoles; Nausea; Serotonin Antagonists; Tropisetron; Vomiting

Topics: Cisplatin; Dose-Response Relationship, Drug; Headache; Humans; Indoles; Serotonin Antagonists; Tropisetron; Vomiting

This review describes clinical experience with tropisetron, a new 5-hydroxytryptamine type 3 (serotonin 3)-receptor antagonist, which was found to possess antiemetic properties in animal studies and pilot studies in chemotherapy-treated patients. Tropisetron 5mg once daily is an effective and well tolerated antiemetic treatment for chemotherapy-induced emesis. Tropisetron can be administered without special precautions to all patients who undergo aggressive chemotherapy, and remains effective during multiple chemotherapy courses. The efficacy of tropisetron compares well with that of the best available complicated antiemetic cocktails, but tropisetron is better tolerated. The simple dosage schedule of either 1 injection or 1 capsule per day makes tropisetron ideal for both inpatient and outpatient treatment.

Topics: Animals; Antiemetics; Antineoplastic Agents; Humans; Indoles; Tropisetron; Vomiting

In recent years a new class of agents, the serotonin type 3 receptor antagonists, has been identified. This article reviews the preclinical, pharmacological and clinical data of ondansetron, granisetron and tropisetron, the first representatives of this group. Preclinical work showed that the drugs interfere with a variety of physiological processes, and hold promise for clinical utility in a wide range of areas. To date, these agents have proven, both in early clinical and comparative studies, to be potent antiemetic agents in patients receiving cisplatin and non-cisplatin chemotherapy as well as radiotherapy. In comparative studies the antiemetic efficacy mostly has been superior to conventional antiemetic drugs with regard to the acute chemotherapy-related symptoms; whereas their role in delayed emesis needs further investigation. This also applies for their role as an antiemetic in other types of nausea and vomiting (post-operative). Toxic effects have been modest, no extrapyramidal reactions have been reported. Potential clinical use in psychiatric disorders has been suggested, and the results of clinical trials are awaited.

Topics: Animals; Antiemetics; Granisetron; Humans; Imidazoles; Indazoles; Indoles; Ondansetron; Serotonin Antagonists; Tropisetron; Vomiting

Topics: Antiemetics; Antineoplastic Agents; Granisetron; Humans; Indoles; Ondansetron; Serotonin Antagonists; Tropisetron; Vomiting

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Granisetron; Headache; Humans; Imidazoles; Indazoles; Indoles; Nausea; Ondansetron; Radiation Injuries; Radiotherapy; Serotonin Antagonists; Tropisetron; Vomiting

These results thus indicate, that ICS 205-930 is a very effective antiemetic for cancer chemotherapy-induced emesis in man. Given as a single dose prior to the chemotherapeutic agent, ICS 205-930 inhibits emesis and nausea for at least 24 hr. Together with the lack of extrapyramidal side-effects, these properties of ICS 205-930 indicate a clear superiority to the current therapeutic standard metoclopramide.

Topics: Animals; Antiemetics; Cats; Cisplatin; Dogs; Drug Evaluation; Ferrets; Humans; Indoles; Nausea; Serotonin Antagonists; Tropisetron; Vomiting

There are no well-recognized guidelines for antiemesis during concurrent chemoradiotherapy (CCRT) for cervical cancer (CC) and nasopharyngeal cancer (NPC) until now. The study was designed to assess the efficacy and safety of fosaprepitant combined with tropisetron and dexamethasone in preventing nausea and vomiting during 5 weeks of fractionated radiotherapy and concomitant weekly low-dose cisplatin chemotherapy in patients with CC or NPC.. Patients with CC or NPC were scheduled to receive fractionated radiotherapy and weekly cisplatin (25-40 mg/m. Between July 2020 and July 2022, 116 patients consented to the study of whom 103 were included in this interim analysis (fosaprepitant group [N = 52] vs control group [N = 51]). The cumulative incidence of emesis at 5 weeks (competing risk analysis) was 25% (95% CI 14.2-37.4) for the fosaprepitant group compared with 59% (95% CI 43.9-71.0) for the control group. There was a significantly lower cumulative risk of emesis in the fosaprepitant group (HR 0.35 [95% CI 0.19-0.64]; p < 0.001). Fosaprepitant was well tolerated as the incidences of adverse events in the two groups were comparable.. The addition of fosaprepitant to tropisetron plus dexamethasone significantly reduced the risk of nausea and vomiting during 5 weeks of CCRT in patients with CC or NPC, and fosaprepitant was well tolerated.. The trial was registered with ClinicalTrials.gov on October 3, 2022, number NCT05564286.

Topics: Antiemetics; Antineoplastic Agents; Cisplatin; Dexamethasone; Dose Fractionation, Radiation; Drug Therapy, Combination; Female; Humans; Nasopharyngeal Neoplasms; Nausea; Prospective Studies; Tropisetron; Uterine Cervical Neoplasms; Vomiting

A prospective randomized controlled trial was conducted to compare 5 mg olanzapine plus standard triple antiemetic therapy for the prevention of nausea and vomiting induced by multiple-day cisplatin chemotherapy.. (1) The primary endpoint CR during OP was 76.0% (45/59) vs 67.0% (41/61) between the quadruple group and triplet group (P = 0.271). The secondary endpoint CR during the AP was significantly higher in the quadruple group than in the triplet group, which was 100.0% (59/59) vs 93.0% (57/61) (P = 0.045). The difference of CR during delayed phase between the groups was especially higher in the quadruple group compared to the triplet group (76.0% (45/59) vs 67.0% (41/61) (P = 0.271)). The rate of patients who achieved total protection in the overall phase was also higher in the quadruple group than the triplet group (28.8% (17/59) vs 23.0% (14/61) (P = 0.463)). During the OP, the incidence of no vomiting in the quadruple group and the triplet group was 93.2% (55/59) vs 80.3% (49/61) (P = 0.038), respectively. (2) Kaplan-Meier curves of time to first emesis were obviously longer in the quadruple group compared with the triplet group (P = 0.031). According to FLIE, no impact of CINV on daily life was defined as total score of questionnaire > 108; this study exhibited identical life quality between two groups. (3) The most common aprepitant- or olanzapine-related AEs included sedation, fatigue, and constipation. The occurrences between two groups were identical.. It may been recommended that 5 mg olanzapine plus tropisetron and dexamethasone, omitting aprepitant triplet regimen as an alternative therapy in prevention CINV induced by multiple-day cisplatin chemotherapy due to the excellent CINV control rate and safety.

Topics: Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Dexamethasone; Humans; Nausea; Olanzapine; Prospective Studies; Quality of Life; Tropisetron; Vomiting

We evaluated the efficacy of electroacupuncture combined with tropisetron in treating carboprost tromethamine-induced nausea and vomiting during cesarean section under lumbar anesthesia.. A total of 264 patients aged 22-40 years were enrolled, who received carboprost tromethamine and suffered nausea and vomiting during cesarean section under lumbar anesthesia. The patients were divided randomly into the control group, electroacupuncture group, tropisetron group, and electroacupuncture + tropisetron group.. Compared to the control group, the nausea and vomiting scores decreased at T3 in both the electroacupuncture and electroacupuncture + tropisetron groups, and decreased at T4 in the electroacupuncture group, tropisetron group, and electroacupuncture + tropisetron group; the motilin, gastrin, and 5-hydroxytryptamine (5-HT) levels decreased at T5 in the other 3 groups. Compared to the electroacupuncture + tropisetron group, the nausea and vomiting scores increased at T3 in the control and tropisetron groups, and increased at T4 in the other 3 groups; the motilin, gastrin, and 5-HT levels increased at T5.. Our study suggested that electroacupuncture combined with tropisetron could effectively relieve carboprost tromethamine-induced nausea and vomiting during cesarean section under lumbar anesthesia. The effect was better than its single application, and the reduced 5-HT, motilin, and gastrin levels might be involved in the underlying mechanism.. Ziel: Wir untersuchten die Wirksamkeit der Elektroakupunktur in Kombination mit Tropisetron bei der Behandlung von Carboprost-Tromethamin-induzierter Übelkeit und Erbrechen während eines Kaiserschnitts in Spinalanästhesie. Methoden: Insgesamt wurden 264 Patientinnen im Alter von 22 bis 40 Jahren, die Carboprost-Tromethamin erhalten hatten und während eines Kaiserschnitts in Spinalanästhesie an Übelkeit und Erbrechen litten, in die Studie aufgenommen. Die Patientinnen wurden randomisiert der Kontrollgruppe, der Elektroakupunktur-Gruppe, der Tropisetron-Gruppe oder der Elektroakupunktur + Tropisetron-Gruppe zugewiesen. Ergebnisse: Im Vergleich zur Kontrollgruppe sanken die Werte für Übelkeit und Erbrechen bei T3 sowohl in der Elektro­akupunktur- als auch in der Elektroakupunktur + Tropisetron-Gruppe und bei T4 in der Elektroakupunkturgruppe, in der Tropisetron-Gruppe und in der Elektroakupunktur + Tropisetron-Gruppe; die Motilin-, Gastrin- und 5-Hydroxytryptamin (5-HT)-Spiegel gingen bei T5 in den anderen drei Gruppen zurück. Im Vergleich zur Elektro­akupunktur + Tropisetron-Gruppe stiegen die Werte für Übelkeit und Erbrechen bei T3 in der Kontroll- und Tropisetron-Gruppe und stiegen bei T4 in den anderen drei Gruppen; die Motilin-, Gastrin- und 5-HT-Konzentrationen stiegen bei T5. Schlussfolgerungen: Unsere Studie spricht dafür, dass Elektroakupunktur in Kombination mit Tropisetron Carboprost-Tromethamin-induzierte Übelkeit und Erbrechen während eines Kaiserschnitts in Spinalanästhesie lindern kann. Der Effekt war stärker ausgeprägt als die alleinige Anwendung, und möglicherweise sind die verringerten 5-HT-, Motilin- und Gastrin-Konzentrationen an dem zugrunde liegenden Mechanismus beteiligt.

Topics: Antiemetics; Carboprost; Cesarean Section; Double-Blind Method; Drug Combinations; Electroacupuncture; Female; Humans; Indoles; Nausea; Pregnancy; Tromethamine; Tropisetron; Vomiting

Greater than 70% of patients with cancer experience chemotherapy-induced nausea and vomiting. In the current study, the authors examined the effects of electrostimulation of the K1 acupoint located on the sole of the foot because it is believed to have the potential to control chemotherapy-induced nausea and vomiting.. In this trial, 103 patients diagnosed with primary or metastatic liver cancer were recruited before transcatheter arterial infusion (TAI) of cisplatin or oxaliplatin and randomized to either group A (51 patients who were treated with the antiemetic tropisetron and acustimulation at the K1 acupoint for 20 minutes approximately 1 to 2 hours before TAI on the first day and then daily for the subsequent 5 days) or group B (52 patients who were treated with tropisetron and electrostimulation at a placebo point on the heel). The rate, intensity, and duration of nausea and vomiting were collected at baseline and then daily for 5 days after TAI. Quality of life was assessed daily using the MD Anderson Symptom Inventory and the EuroQoL scale.. No differences were found between groups A and B with regard to the incidence and degree of nausea or vomiting on day 1 or the following 5 days. Patients in group A had better EuroQoL scores compared with patients in group B (72.83 in group A vs 65.94 in group B; P =.04) on day 4 but not on the other days. No group differences were noted at any time point for MD Anderson Symptom Inventory scores.. Electrostimulation of K1 combined with antiemetics did not result in initial prevention of cisplatin-induced or oxaliplatin-induced nausea or vomiting.

Topics: Acupuncture Points; Antiemetics; Antineoplastic Agents; Cisplatin; Combined Modality Therapy; Electroacupuncture; Heel; Humans; Indoles; Liver Neoplasms; Nausea; Organoplatinum Compounds; Oxaliplatin; Tropisetron; Vomiting

To assess, in a prospective, observational study, the safety and efficacy of the addition of the neurokinin-1-receptor antagonist (NK1-RA) aprepitant to concomitant radiochemotherapy, for the prophylaxis of radiation therapy-induced nausea and vomiting.. This prospective observational study compared the antiemetic efficacy of an NK1-RA (aprepitant), a 5-hydroxytryptamine-RA, and dexamethasone (aprepitant regimen) versus a 5-hydroxytryptamine-RA and dexamethasone (control regimen) in patients receiving concomitant radiochemotherapy with cisplatin at the Department of Radiation Oncology, University Hospital Halle (Saale), Germany. The primary endpoint was complete response in the overall phase, defined as no vomiting and no use of rescue therapy in this period.. Fifty-nine patients treated with concomitant radiochemotherapy with cisplatin were included in this study. Thirty-one patients received the aprepitant regimen and 29 the control regimen. The overall complete response rates for cycles 1 and 2 were 75.9% and 64.5% for the aprepitant group and 60.7% and 54.2% for the control group, respectively. Although a 15.2% absolute difference was reached in cycle 1, a statistical significance was not detected (P=.22). Furthermore maximum nausea was 1.58 ± 1.91 in the control group and 0.73 ± 1.79 in the aprepitant group (P=.084); for the head-and-neck subset, 2.23 ± 2.13 in the control group and 0.64 ± 1.77 in the aprepitant group, respectively (P=.03).. This is the first study of an NK1-RA-containing antiemetic prophylaxis regimen in patients receiving concomitant radiochemotherapy. Although the primary endpoint was not obtained, the absolute difference of 10% in efficacy was reached, which is defined as clinically meaningful for patients by international guidelines groups. Randomized phase 3 studies are necessary to further define the potential role of an NK1-RA in this setting.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Chemoradiotherapy; Cisplatin; Dexamethasone; Drug Therapy, Combination; Esophageal Neoplasms; Female; Head and Neck Neoplasms; Humans; Indoles; Lung Neoplasms; Male; Middle Aged; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Ondansetron; Prospective Studies; Serotonin Antagonists; Tropisetron; Uterine Cervical Neoplasms; Vomiting

We aimed to compare the relative efficacy of tropisetron and metoclopramide in treating nausea/vomiting in undifferentiated ED patients.. We undertook a randomized, double-blinded, clinical trial. Adult patients requiring treatment for nausea/vomiting were randomly assigned to either tropisetron (5 mg) or metoclopramide (10 mg), by i.v. bolus. The primary end-point was incidence of vomiting. Secondary end-points were decrease in nausea score from baseline (0-100 VAS), the requirement of 'rescue' anti-emetics, ongoing nausea over 48 h and side-effects.. Fifty patients were enrolled in each group. The demographic variables, presenting complaints and nausea scores at baseline did not differ (P > 0.05). By 180 min, two (4.0%) and nine (18.0%) patients had vomited in the tropisetron and metoclopramide groups respectively (difference 14.0%, 95% CI 0.1-28.0, P= 0.05). Also, there were two and 20 episodes of vomiting respectively. Vomiting rates were 0.02 and 0.16 episodes/person-hour (difference 0.14 episodes/person-hour, 95% CI 0.07-0.21, P < 0.001) respectively. By 60 min and thereafter, the decrease in nausea score from baseline was greater (although not significantly so) in the tropisetron group. At 180 min, the decreases were 47.9 mm and 37.0 mm respectively (difference 10.9 mm, 95% CI -0.7-22.6). Five (10.0%) and 13 (26.0%) patients required a rescue anti-emetic respectively (difference 16.0%, 95% CI -0.7-32.7, P= 0.07). Of patients followed up, 13/47 (27.7%) and 20/49 (40.8%) had ongoing nausea respectively (difference 13.2%, 95% CI -7.7-34.0, P= 0.25). The tropisetron group had less akathisia.. Tropisetron was associated with a significantly lower vomiting rate and shows promise as an alternative anti-emetic in the ED.

Topics: Adult; Aged; Antiemetics; Double-Blind Method; Emergency Medical Services; Emergency Service, Hospital; Female; Humans; Incidence; Indoles; Male; Metoclopramide; Middle Aged; Nausea; Tropisetron; Vomiting; Young Adult

To compare the antiemetic efficacy and tolerability of tropisetron plus metopimazine with tropisetron plus placebo during 4 cycles of multiple-day, cisplatin-based chemotherapy.. 82 chemotherapy-naive patients with germ cell cancer scheduled to 4 cycles of multiple-day cisplatin-based chemotherapy (20 or 40 mg/m(2)/day for 5 days) given every 3 weeks were included. A double-blind parallel trial design was used and patients randomized to tropisetron plus metopimazine or tropisetron plus placebo. Tropisetron was administered as a single 5 mg intravenous dose on days 1-5 and a single 5 mg oral dose on day 6, and metopimazine as 30 mg orally t.i.d. on day 1, and q.i.d on days 2-6.. Patients were evaluable for efficacy during a total of 195 cycles. Small, but certain advantages were obtained with the combination. In cycle 1, complete protection from emetic episodes on day 1, days 1-5, days 6-9 and days 1-9 was achieved in 85.7%, 42.9%, 86.2% and 40.5% with tropisetron plus metopimazine and in 90.0%, 22.5%, 64.3% and 17.5% with tropisetron plus placebo, respectively. This difference achieved statistical significance in the overall period, days 1-9 (P = 0.029). During the entire period (days 1-9), significantly less nausea was seen in patients receiving tropisetron plus metopimazine (P = 0.027), whereas other nausea parameters did not reach statistical significance. The cumulative emetic protection rate after 4 cycles was 0.51 with tropisetron plus metopimazine and 0.25 with tropisetron plus placebo (P = 0.037). Side effects were generally few and mild with both treatments and no significant differences were seen.. Tropisetron plus metopimazine is superior to tropisetron during 4 cycles of multiple-day cisplatin-based chemotherapy, but both treatments are ineffective in a number of patients. The effect of the combination seems comparable to that of ondansetron plus dexamethasone. Newer drugs such as the neurokinin(1) receptor antagonist, aprepitant, should be investigated to optimize antiemetic therapy in patients receiving multiple-day chemotherapy.

Topics: Adolescent; Adult; Antiemetics; Antineoplastic Agents; Cisplatin; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Indoles; Isonipecotic Acids; Male; Middle Aged; Nausea; Neoplasms, Germ Cell and Embryonal; Tropisetron; Vomiting

Tropisetron hydrochloride (Navoban), as a highly selective 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, has been widely used in preventing and treating chemotherapy-induced nausea and vomiting for many years. This study was to evaluate the efficacy and safety of homemade tropisetron hydrochloride in preventing and treating cisplatin-based chemotherapy-induced nausea and vomiting.. A randomized, double-blinded, multicenter, comparative trial was conducted in cancer patients receiving cisplatin-based chemotherapy. All patients were assigned to group A-B or B-A randomly, and took homemade tropisetron hydrochloride and Navoban (positive control agent) to treat chemotherapy-induced nausea and vomiting.. A total of 118 patients were enrolled: 60 in group A-B and 58 in group B-A. There was no difference in the efficacy of relieving acute vomiting between homemade tropisetron hydrochloride and Navoban (P>0.05). The inhibition rates of nausea and vomiting were 28.59% and 52.61% respectively in group A-B, while 29.21% and 51.94% in group B-A (P>0.05). In addition, quality of life (QOL) showed no significant difference between the 2 groups at Days 3, 6, 10, and 21 (P>0.05). Besides, the occurrence rate of adverse events, such as constipation, abdominal distention, vertigo, headache and fatigue, was 27.97% in group A-B and 22.03% in group B-A (P>0.05).. Homemade tropisetron hydrochloride injection has both reliable efficacy and safety in preventing and treating cisplatin-induced acute or chronic nausea and vomiting; it is comparable with Navoban on many aspects, such as long action time, less adverse effects and improved QOL.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Double-Blind Method; Female; Humans; Indoles; Male; Middle Aged; Nausea; Neoplasms; Quality of Life; Serotonin Antagonists; Tropisetron; Vomiting

A prospective randomized open label study was carried out to evaluate the efficacy and effectiveness of prophylactic tropisetron versus rescue tropisetron in fractionated radiotherapy.. The study sample consisted of 288 cancer patients randomly allocated (3:4 ratio) into two treatment groups: 120 patients received prophylactic antiemetic treatment with tropisetron and 168 patients received rescue tropisetron. To determine the efficacy of prophylactic antiemetic treatment, nausea and vomiting were evaluated 1 d before radiation therapy (RT), at 24 and 72 h, at the end of every week during RT, and finally 1 wk after RT. Diary cards were used to record the intensity of nausea and vomiting as well as the incidence of adverse effects.. In the odds of nausea and vomiting, statistically significant differences were found between the two treatment groups over time. The incidence of nausea and vomiting were 1.89 (p = 0.009) and 2.19 (p = 0.001) times higher in the rescue tropisetron group than in the prophylactic tropisetron group. Factors that related significantly with increased nausea were primary cancer, rescue tropisetron, and radical RT. Moreover, factors for vomiting were primary cancer type, metastasis, palliative RT, and rescue tropisetron.. Higher numbers of patients receiving prophylactic tropisetron completed RT with lower incidence of nausea and vomiting than those in the rescue tropisetron group.

Topics: Aged; Antiemetics; Dose Fractionation, Radiation; Female; Humans; Indoles; Male; Middle Aged; Nausea; Neoplasms; Prospective Studies; Tropisetron; Vomiting

The antiemetic efficacy and tolerability of Tropisetron (Navoban, Novartis Pharma Switzerland AG, Bern), a selective 5-hydroxytriptamine receptor antagonist, has been assessed in the prevention of acute vomiting in children receiving chemotherapy for solid tumors. Tropisetron iv was given 30 min before administration of chemotherapy at a dose of 5 mg in children <20 kg body weight and at a dose of 10 mg in those >20 kg. A total of 50 children were studied in 189 courses of chemotherapy. Control of emesis was defined as total in absence of acute vomiting, as major if 1 or 2 events of acute vomiting occurred, and as not controlled if >2 events of acute vomiting occurred. Response was studied, taking into account Tropisetron dosage, degree of emetogenicity of the chemotherapeutic agents in pretreated and non-pretreated patients, and according to age groups. Tropisetron, administered in a single daily dose of 8-12 mg/m(2), was found to be very effective in completely controlling acute emesis in 92% of the courses of moderately and highly emetogenic chemotherapy administered to pediatric patients with solid tumors. Moreover, Tropisetron, at this dosage, did not lead to any adverse effects.

Topics: Adolescent; Adult; Age Factors; Analysis of Variance; Antiemetics; Antineoplastic Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Humans; Indoles; Infant; Infusions, Intravenous; Male; Tropisetron; Vomiting

Resistance to antiemetic treatment with 5-hydroxytryptamine type 3 (5-HT(3)) receptor antagonists is still a major problem resulting in patient discomfort and poor compliance to chemotherapy. We hypothesized that clinical resistance to 5-HT(3) antagonists is associated with the single-nucleotide polymorphism (3435C>T) in the gene that codes for the drug efflux transporter adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1).. Patients with cancer (N = 216) treated with chemotherapeutic regimens composed of highly or moderately emetogenic agents were examined for their antiemetic responses to tropisetron, ondansetron, or granisetron. The efficacy of antiemetic treatment was documented by self-report charts for 5 days after chemotherapy. ABCB1 3435C>T genotype was determined to analyze its association with the antiemetic efficacy of 5-HT(3) antagonists.. Within the first 24 hours of chemotherapy, the complete control rate of nausea and vomiting was higher in subjects with the ABCB1 TT genotype (n = 49) as compared with those with the CC (n = 60) or CT (n = 107) genotype (P = .044). The type of 5-HT(3) antagonists influenced the effect of genotype on antiemetic responses. The complete control rates were 92.9% in TT subjects (n = 14) in comparison to homozygote (47.6%, n = 21, P = .009) or heterozygote (56.1%, n = 41, P = .02) carriers of the 3435 C allele in granisetron-treated patients. However, during the delayed phase of chemotherapy, the complete control rates did not differ across genotypes.. These results suggest that ABCB1 3435C>T polymorphism is associated with antiemetic treatment efficacy in patients with cancer treated with 5-HT(3) antagonists, particularly in granisetron-treated patients, during the short-term phase of chemotherapy.

Topics: Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; ATP-Binding Cassette Transporters; Female; Gene Frequency; Genotype; Granisetron; Humans; Indoles; Male; Middle Aged; Nausea; Neoplasms; Ondansetron; Polymorphism, Single Nucleotide; Prospective Studies; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Time Factors; Treatment Outcome; Tropisetron; Vomiting

High-dose conditioning regimens of chemo-radiotherapy with or without total body irradiation (TBI) frequently induces nausea and vomiting in patients who are supported with stem cell transplantation. 5-Hydroxytrypamine(3) (5-HT(3)) receptor antagonists, when used alone, are unsatisfactory in the attenuation of emesis; Furthermore, consensus about their optimal dose, optimal dosing frequency and the combined use with other anti-emetic drugs are still controversial. The main objective of this trial was to observe the anti-emetic effectiveness and side effects of tropisetron plus dexamethasone and diphenhydramine (Group A) and tropisetron alone (Group B) on the patients undergoing high-dose treatment for peripheral blood stem cell (PBSC) mobilization and transplantation.. From December 1998 to September 2002, 68 patients undergoing autologous peripheral blood stem cell transplantation were allotted into this study. All the eligible patients were divided into group A or B non-randomly to compare the efficacy of the two regimens in the prevention of nausea and vomiting induced by high-dose treatment. Regimens:40 patients in group A were given tropisetron 5 mg,iv,every 12 h plus dexamethasone 5-10 mg, iv, daily, and diphenhydramine, 20 mg, im, daily. Twenty-eight patients in group B were received tropisetron alone,5 mg,iv,every 12h.. For nausea during the acute phase, complete response rates of group A and B were 55% and 46.4%, with an overall response rates of 97.5% and 85.7%,of which the difference was insignificant (P >0.05). For vomiting during the acute phase, complete response rates of group A and B were 77.5% and 78.6%, with an overall response rates of 90% and 92.9%, of which the difference was insignificant (P >0.05). For delayed phase, both the complete response and overall response rates were higher in group A, with the difference significant (P< 0.05). The side effects of both regimens were mild. Common side effects including abdomen discomfort,headache,heavy head and constipation did not necessitate the discontinuity of high-dose treatment.. The combination of tropisetron with dexamethasone and diphenhydramine is more effective than tropisetron alone in the control of nausea and vomiting induced by high-dose chemotherapy with or without TBI, which is especially more effective in the delayed phase of nausea and vomiting. The side effects of the combination regimen were mild. Based on these findings, we stress the importance of large randomized trials in the future.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Child; Combined Modality Therapy; Female; Humans; Indoles; Male; Nausea; Neoplasms; Peripheral Blood Stem Cell Transplantation; Radiotherapy; Transplantation, Autologous; Tropisetron; Vomiting

The antiemetic effectiveness of 5-HT3 receptor antagonists in combination with dexamethasone in patients receiving short-term infusion chemotherapy has been well demonstrated. Less information is available about the efficacy of the same antiemetic combination in patients treated with regimens of chemotherapy in which the drugs are delivered in continuous infusion of several hours. The purpose of this study was to report the effectiveness of a double administration of antiemetic drugs in patients treated with strong emesis-inducing drugs for several days. In this study, 19 male and 13 female patients with osteosarcoma, ages 9 to 45 years, treated with chemotherapy, received intravenous tropisetron 5 mg plus dexamethasone 8 mg every 12 hours during the first two cycles of the preoperative treatment: cisplatin 120 mg/m2 over 48 hours followed by Adriamycin 75 mg/m2 delivered in 24 hours and continuous infusion of ifosfamide 15 g/m2 over 120 hours. The assessment of the antiemetic efficacy was performed three times every day: from 8:00 am to 4:00 pm, from 4:00 pm to 12:00 am, and from 12:00 am to 8:00 am. The patients were followed from the beginning of the treatment until 2 hours after its end, when they were discharged from hospital. Complete protection from emesis was obtained in 80% of the 256 days of treatment: 81% during the first cycle (cisplatin 120 mg/m2 in 48 hours followed by Adriamycin 75 mg/m2 delivered in 24 hours) and 79% during the second cycle (continuous infusion of ifosfamide 15 g/m2 in 120 hours). In both cycles, complete protection declined from the first to the last day of treatment (from 100% to 62% during the first cycle and from 100% to 63% during the second cycle). These results indicate that when chemotherapy is administered in a protracted infusion, higher doses of antiemetic agents are necessary to achieve acceptable antiemetic activity.

Topics: Acute Disease; Adolescent; Adult; Antiemetics; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Child; Cisplatin; Dexamethasone; Doxorubicin; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Ifosfamide; Indoles; Infusions, Intravenous; Male; Middle Aged; Osteosarcoma; Serotonin Antagonists; Time Factors; Treatment Outcome; Tropisetron; Vomiting

To study the enhancement by dexamethasone of the effect of ondansetron and tropiesetron against postoperative nausea and vomiting (PONV) in patients receiving patient-controlled analgesia (PCA) and observe the effect of dexamethasone on wound healing.. One hundred and twenty elective surgical patients receiving PCA were divided into 4 groups, including 2 control groups with the prescription of ondansetron (8 mg) and tropiesetron (3 mg) respectively (control A and B) and 2 observation groups in which the patients were given ondansetron (8 mg) plus dexamethasone (10 mg) and tropiesetron (3 mg) plus dexamethasone (10 mg) respectively (observation groups C and D). The incidence and severity of PONV was observed at 4, 8, 2, 24 h and 2, 3 d postoperatively, and the time and grade of healing of the wound evaluated.. Significant difference in PONV between group A and group B was observed (P<0.01), and in the observation groups, PONV was markedly reduced compared with the control groups (C vs A, P<0.01; D vs B, P<0.05). In light of the time and grade of wound healing, the observation groups differed little from the control groups.. Dexamethasone (10 mg) can greatly enhance the effect of ondansetron and tropiesetron against PONV in patients receiving PCA without interfering the healing of the wound.

Topics: Analgesia, Patient-Controlled; Anti-Inflammatory Agents; Antiemetics; Dexamethasone; Drug Synergism; Drug Therapy, Combination; Humans; Indoles; Nausea; Ondansetron; Treatment Outcome; Tropisetron; Vomiting; Wound Healing

The use of serotonin 5-hydroxytryptamine type 3 receptor antagonists has substantially reduced, but not eliminated, nausea and vomiting in cancer chemotherapy. This study sought to investigate whether efficacy of antiemetic treatment with ondansetron and tropisetron depends on cytochrome P-450 2D6 (CYP2D6) genotype, hypothesizing that the rapid and particularly the ultrarapid metabolizers of these drugs are at risk of being undertreated.. Included in the study were 270 cancer patients receiving their first day of chemotherapy. Nausea and vomiting were documented using standardized interviews. The intensity of nausea was measured with visual analog scales before and twice during the chemotherapy. The relationship between the CYP2D6 genotypes and the tropisetron serum concentrations 3 and 6 hours after drug administration was analyzed in a subgroup of 42 patients. CYP2D6 genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism analysis.. Genetically defined poor metabolizers had higher serum concentrations of tropisetron than all other patients (P <.03). Approximately 30% of all patients receiving chemotherapy experienced nausea and vomiting. Genetically defined ultrarapid meta-bolizers of CYP2D6 substrates had higher frequency of vomiting within the first 4 hours (P <.001) and within the period 5 to 24 hours (P <.03) after treatment than all the other patients; the tendency for nausea was similar. This difference was more pronounced in patients treated with tropisetron than in those treated with ondansetron.. Antiemetic treatment with tropisetron or ondansetron could be improved by adjustment for the CYP2D6 genotype; approximately 50 subjects would have to be genotyped to protect one patient from severe emesis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Cytochrome P-450 CYP2D6; Female; Gene Expression Profiling; Genetic Predisposition to Disease; Genotype; Humans; Indoles; Male; Middle Aged; Nausea; Neoplasms; Ondansetron; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Predictive Value of Tests; Prospective Studies; Risk Factors; Serotonin Antagonists; Tropisetron; Vomiting

Tropisetron and granisetron are selective serotonin (5-HT3) antagonists that have been proven effective in the prevention of nausea and vomiting in adults and children receiving cancer chemotherapy. This prospective, randomised study was designed to compare the efficacy of the two agents in the prevention of vomiting and nausea in children receiving highly emetogenic chemotherapy for various malignancies. A total of 51 children (mean age: 7.7 +/- 4.8 year) were studied in 133 chemotherapy cycles. In 66 chemotherapy cycles, the children received tropisetron as an antiemetic agent in a dose of 0.2 mg/kg/24 h intravenously and, in 67 cycles, they received granisetron 40 micrograms/kg/24 h intravenously before cytotoxic drug administration during the days they received chemotherapy. The response per 24 h of chemotherapy was defined as complete (no nausea and vomiting), partial (1-4 events of vomiting and/or nausea), and failure (more than 4 events of vomiting and/or nausea). Efficacy of antiemetic therapy was evaluated as acute (Day 1) and overall was based on the worst day during the chemotherapy. Complete control of acute vomiting was achieved in 74% of tropisetron and 88% of granisetron patients (P = 0.04), and complete control of acute nausea in 56% and 82% respectively (p = 0.002). Overall response by means of complete control of both vomiting and nausea during the whole therapy period was 29% of tropisetron group and 55% of granisetron group (p = 0.007). The statistical analysis (depending on the emetogenicity of the chemotherapy cycles) showed increased efficacy of granisetron in highly (grade 3) emetogenic chemotherapy cycles (p = 0.002), whereas there was no difference in the very highly emetogenic cycles (p = 0.7). Also, granisetron was found to be more effective than tropisetron, especially in patients heavier than 25 kg (p = 0.02). The adverse reactions were few and mild. There were no differences in the tolerability of the two antiemetic therapy modalities. In conclusion, granisetron was found to be more effective than tropisetron in controlling nausea and vomiting in children receiving highly emetogenic chemotherapy. This increased antiemetic efficacy of ganisetron might have been related to maximal dose differences according to body weight.

Topics: Adolescent; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Female; Granisetron; Humans; Indoles; Infant; Male; Nausea; Prospective Studies; Therapeutic Equivalency; Treatment Outcome; Tropisetron; Vomiting

The objective of this study was to evaluate the efficacy and safety of ramosetron hydrochloride for the management of nausea and vomiting induced by chemotherapy in patients with hematological malignancies. A total of 30 patients with hematological malignancies were included in the ramosetron group. Ramosetron (0.3 mg i.v.) was administered 0.5 h before chemotherapy. The impact of ramosetron on anorexia, nausea and vomiting as well as other adverse effects were assessed. Meanwhile, another 39 patients received tropisetron (o.d. for 3 days). As compared to the tropisetron group, the response rate of the ramosetron group in controlling anorexia within 18-24 h after chemotherapy was higher (p < 0.05); within 18-24 h after chemotherapy, the complete response rate and effective rate in controlling nausea was higher (p < 0.05); within 12-18 h and 18-24 h after chemotherapy, the complete response rate and effective rate in controlling vomiting was higher (p < 0.05). The incidence of adverse effects was similar in both groups. We conclude that ramosetron belongs to a new generation of 5-HT3 receptor antagonists and that it is a safe, economic and effective antiemetic drug.

Topics: Adolescent; Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Appetite; Benzimidazoles; Constipation; Dizziness; Drug-Related Side Effects and Adverse Reactions; Female; Flushing; Gastrointestinal Diseases; Headache; Hematologic Neoplasms; Humans; Indoles; Male; Middle Aged; Nausea; Thirst; Treatment Outcome; Tropisetron; Vomiting

The rates of delayed nausea and vomiting by moderately emetogenic chemotherapy in patients with previous experience of acute emesis are usually quite high. This is a pilot study aiming to evaluate the safety of a new antiemetic schedule to prevent delayed emesis in this subset of patients. During 5 consecutive cycles of moderately emetogenic chemotherapy, we evaluated 50 patients (15 males) who experienced acute emesis in the first cycle of treatment. The regimen for prevention of delayed emesis consisted of daily tropisetron (5 mg orally from d 2 to d 6 of each chemotherapeutic cycle) associated to ACTH-Depot (1 mg intramuscularly 24 and 68 h after the initiation of chemotherapy). In 77% of chemotherapy cycles, there was a total elimination of nausea and vomiting, whereas in the remaining 23% of cycles, there was a major response defined as < or = 2 vomiting episodes per cycle or nausea grade 1 according to the WHO. The efficacy of the antiemetic regimen persisted during the entire treatment program without the appearance of toxic effects. The proposed antiemetic regimen is highly active in preventing delayed nausea and vomiting episodes in patients receiving moderately emetogenic chemotherapy. Moreover, no toxic effects were observed. These promising results require confirmation by a randomized trial.

Topics: Administration, Oral; Adrenocorticotropic Hormone; Adult; Aged; Antiemetics; Antineoplastic Agents; Delayed-Action Preparations; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Indoles; Injections, Intramuscular; Male; Middle Aged; Recurrence; Tropisetron; Vomiting

To compare the efficacy and adverse effects of Tropisetron with Kytril in the prevention of nausea and vomiting induced by anti-cancer drugs.. In a clinical randomized controlled cross-over trial, 34 patients (19 among them treated with regimens containing cisplatin) were randomized into A and B group. In group A, Tropisetron was given in the first cycle and Kytril in the second cycle, while in group B Kytril was given in the first and Tropisetron in the second cycle of the same chemotherapy.. In the Tropisetron treated group, the response rate was 97.1% with 4.5 episodes of vomiting on the first day of chemotherapy, while that in the Kytril treated patients was 94.1% with 3 episodes of vomiting. There was no statistical difference between the 2 groups. Control of delayed emesis and other adverse reactions were comparable in both arms and there was no notable difference between Tropisetron and Kytril.. Tropisetron is an effective anti-emetic drug to prevent nausea and vomiting caused by anti-tumor agents, and its adverse reactions are mild.

Topics: Adolescent; Adult; Aged; Antiemetics; Antineoplastic Agents; Cross-Over Studies; Drug Administration Schedule; Female; Granisetron; Humans; Indoles; Male; Middle Aged; Nausea; Tropisetron; Vomiting

The purpose of this study was to evaluate the effectiveness of three 5-HT3 antagonists in routine clinical practice. The ultimate aim was to develop an antiemetic protocol, selecting a single 5-HT3 antagonist. Each of the drugs was studied for a 4-month period and data was collected from patients on nausea, vomiting (both acute and delayed) and side-effects by means of a diary card. A total of 274 patients were enrolled into the study. Success rates for acute emesis seen over the study period were in excess of 90%. There were no statistically significant differences between any of the three drugs investigated with respect to both acute and delayed nausea and vomiting. Similarly, there was no difference between the three groups for the incidence of constipation, diarrhoea and headache. Granisetron demonstrated a lesser deviation from the protocol in respect of the number of intravenous doses given to patients. The study allowed an effective 5-HT3 antagonist protocol to be developed for use in the management of nausea and vomiting in cancer patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Clinical Protocols; Female; Granisetron; Humans; Indoles; Male; Middle Aged; Nausea; Neoplasms; Ondansetron; Receptors, Serotonin; Receptors, Serotonin, 5-HT3; Serotonin Antagonists; Treatment Outcome; Tropisetron; Vomiting

The antiemetic efficacy of granisetron, ondansetron and tropisetron was evaluated in patients treated with cisplatin-Adriamycin (CDP/ADM) and ifosfamide (IFO) by continuous infusion (CI). In all, 90 patients with osteosarcoma were randomly assigned to receive granisetron (2 mg/m2), or ondansetron (5.3 mg/m2), or tropisetron (3.3 mg/m2) plus dexamethasone 8 mg/m2. Chemotherapy consisted of CDP (120 mg/m2, 48-h CI) followed by ADM (75 mg/m2, 24-h CI) and then, in the second cycle, delivered 3 weeks later, IFO 15 g/m2 (120-h CI). Complete protection (CP) from emesis was obtained on 59% of the 717 days of treatment, without significant differences among the three study drugs. A significantly higher rate of CP was obtained during chemotherapy with IFO than with CDP/ ADM (69% vs 44%; P<0.0001). The rate of CP declined from the first to the last day of treatment for both CDP/ADM (61% to 27%, P<0.0001) and IFO (95% to 43%) cycles (P<0.0001). When CDP/ ADM and IFO are delivered on multiple days by CI, granisetron, ondansetron and tropisetron have the same antiemetic efficacy, which declines from the first day onward through successive days.

Topics: Acute Disease; Adolescent; Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Child; Child, Preschool; Cisplatin; Doxorubicin; Drug Administration Schedule; Extremities; Female; Granisetron; Humans; Ifosfamide; Indoles; Male; Ondansetron; Osteosarcoma; Tropisetron; Vomiting

The purpose of this study was to compare the antiemetic efficacy of three 5-HT3 antagonists (granisetron, ondansetron, tropisetron) plus dexamethasone for the prevention of acute emesis induced by high-dose cisplatin chemotherapy. This was a randomized, open label, crossover study. Recruited into the study were 94 chemotherapy-naive patients of whom five were excluded because chemotherapy was not given, noncisplatin regimen was used instead, or presence of anticipatory vomiting. The remaining 89 evaluable patients were mostly (86.5%) male, and were all treated for head and neck cancers. The antiemetic regimens consisted of 1) granisetron 3 mg i.v. and dexamethasone 20 mg i.v. on day 1 (GRADEX); 2) tropisetron 5 mg i.v. and dexamethasone 20 mg i.v. on day 1 (TRODEX); and 3) ondansetron 8 mg i.v. and dexamethasone 20 mg i.v. to be followed by ondansetron 8 mg p.o. x 2 on day 1 (ONDEX). Patients were randomized to receive one of the three regimens in the first cycle, and treatment was crossed over to the other two regimens in subsequent cycles. Antiemetic efficacy was assessed using self-report diaries recording the number of vomiting episodes as well as duration and severity of nausea within the first 24 hours. Complete response was defined as no vomiting with or without mild nausea, and major response was defined as one vomiting episode and/or moderate to severe nausea. Major efficacy refers to either complete or major response. A total of 219 cycles was given to 89 patients: 16 received one cycle only, 16 received two cycles, and 57 received three cycles. No carryover effects were observed between cycles. Using pooled data from all cycles, the complete response rates to GRADEX, TRODEX, and ONDEX were 81%, 68%, and 71%, respectively (p = 0.11); the corresponding major efficacy rates were 91%, 93%, and 86%, respectively (p = 0.36). When only the first cycle was considered, the complete response rates to GRADEX, TRODEX, and ONDEX were 81%, 75%, and 74%, respectively (p = 0.58); the corresponding major efficacy rates were 92%, 94%, and 84%, respectively (p = 0.38). Analysis of the crossover data showed that the majority of patients achieved complete response or major efficacy with the different pairs of regimens, and there were no significant differences between different regimens in terms of complete response or major efficacy. The only exception was GRADEX versus TRODEX, in which 15.5% of patient achieved complete response with GRADEX as compared with 1.7%

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Cisplatin; Cross-Over Studies; Dexamethasone; Female; Granisetron; Head and Neck Neoplasms; Humans; Indoles; Injections, Intravenous; Male; Middle Aged; Ondansetron; Patient Satisfaction; Treatment Outcome; Tropisetron; Vomiting

The efficacy of an intravenous 5-HT3 antagonist (granisetron) and four oral 5-HT3 antagonists (granisetron, ondansetron, tropisetron and ramosetron) on chemotherapy-induced emesis were investigated in 21 gynecologic cancer patients (63 courses). The severity of emesis after chemotherapy was classified in 4 grades (0: none, 1: slight loss of appetite, 2: severe loss of appetite, but tolerable, and 3: untolerable). The effect of 5-HT3 antagonists was judged by both the score for the severity of the emesis and the frequency of vomiting. The four oral 5-HT3 antagonists were almost the same in efficacy for 5 days after chemotherapy. Oral 5-HT3 antagonists were almost equipotent to intravenous granisetron for JT (paclitaxel + carboplatin) therapy or T (paclitaxel) therapy for 5 days after chemotherapy. However, they were ineffective for CAP (cisplatin + adriamycin + cyclophosphamide) therapy. From these results, oral 5-HT3 antagonists were proved to have a sufficient anti emetic effect after chemotherapy in cases of JT or T therapy. However, in cases of CAP therapy, intravenous 5-HT3 antagonists were thought to be preferable for the control of emesis due to chemotherapy.

Topics: Administration, Oral; Antiemetics; Benzimidazoles; Carboplatin; Cisplatin; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Genital Neoplasms, Female; Granisetron; Humans; Indoles; Middle Aged; Nausea; Ondansetron; Paclitaxel; Serotonin Antagonists; Tropisetron; Vomiting

The goals of this work were to compare the relative efficacy of ondansetron, granisetron and tropisetron in a randomised double blind crossover trial, evaluating objective, subjective and pharmacoeconomic parameters. To this end, 136 patients were enrolled, 120 of whom were eligible and evaluable. Each patient received three identical chemotherapy cycles with an antiemetic protocol which consisted in dexamethasone 20 mg i.v. and a tapering dose schedule for 4 days, and a single i.v. dose of an antiserotoninergic drug in each cycle. Arm A patients received tropisetron 5 mg; arm B patients, granisetron 3 mg; and arm C patients, ondansetron 24 mg. Numbers of patients and days with emetic episodes, grade of nausea, patient preference, headaches, need for metoclopramide, nursing or medical consultation, or admission to emergency room or ward were evaluated. There was no difference in the percentage incidence of acute or delayed nausea and vomiting. Twenty-five per cent of patients preferred tropisetron, 30% preferred granisetron, and 45% preferred ondansetron (P<0.01). Toxicity was mild in less than 10% of patients. Direct and indirect costs of treatment varied from 19.74 to 28.53 euros for tropisetron, 31.07-46.51 euros for granisetron and 22.76-62.61 euros for ondansetron. There was no difference in objective activity. In the schedules studied, patients preferred ondansetron. Indirect costs amount to less than 10% of the total antiemetic cost. Direct costs varied widely and should be considered whenever an antiemetic drug is selected.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Cost-Benefit Analysis; Cross-Over Studies; Drug Costs; Female; Granisetron; Health Care Costs; Humans; Indoles; Male; Middle Aged; Nausea; Neoplasms; Ondansetron; Treatment Outcome; Tropisetron; Vomiting

Thirty-one patients treated with 58 cycles of cisplatin-based chemotherapy at a dose > 80 mg/m2 were enrolled into the study using tropisetron and dexamethasone in the prevention, of cisplatin-induced emesis. There was 87.9 per cent complete control, 10.3 per cent major control, and 1.7 per cent failure for nausea episode on the first day of cycle. For the vomiting control, there was 96.6 per cent complete control, 3.4 per cent major control, and no failure. After the second day, the percentage of complete control increased gradually for both nausea and vomiting. The complete control for acute nausea and vomiting was 85.7 per cent and 92.9 per cent, respectively. The efficacy for delayed emesis was lower. There was 76.4 per cent complete control for delayed nausea and 85.7 per cent for delayed vomiting. The treatment was well tolerated without any serious adverse events related to tropisetron. Only hiccups was reported in 4 patients and recovered spontaneously at the end of the cycle. Combination of tropisetron and dexamethasone is an effective and safe antiemetic regimen in the prevention of cisplatin-induced emesis.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Cisplatin; Dexamethasone; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Indoles; Male; Middle Aged; Treatment Outcome; Tropisetron; Vomiting

The aim of this study was to compare antiemetic efficacy of three serotonin antagonists, granisetron, tropisetron and ondansetron, during conditioning for autologous stem cell transplantation (ASCT). Forty-five malignant lymphoma patients (mean age 38 years, M:F 30:15), undergoing the highly emetogenic regimen BEAM prior to ASCT, were randomized to receive IV granisetron (G) 3 mg once a day, IV tropisetron (T) 5 mg once a day, or IV ondansetron (0) 8 mg twice daily, for six days. The treatment groups were comparable with respect to age, sex and previous experience of nausea and/or vomiting. Nausea and/or emesis control failure was defined as a nausea lasting > or = 4 hours and/or > or = 3 episodes of vomiting/24 h, emesis control failure as > or = 3 episodes of vomiting/24 h. Both the period of chemotherapy (6 days) and the whole period of observation (10 days) were evaluated. Nausea and/or emesis control failure occurred in 24% of patients during the period of chemotherapy and in 51% of patients throughout the whole period of observation, while emesis control failed in 2% and 27% of patients, respectively. The efficacy of three serotonin antagonists was comparable during the chemotherapy period (5 patients with nausea and/or emesis control failure in the granisetron group, 2 in the tropisetron group and 4 in the ondansetron group,p = 0.40). When evaluating the whole period of observation, the antiemetic response to G and T was significantly better than to O, nausea and/or emesis control failure having occurred in 7 (47%) patients treated with G, 5 (33%) patients treated with T, and 12 (80%) patients treated with O, p = 0.03. The results concerning emesis control failures were similar, G 4 (27%), T 1 (7%), O 7 (47%), p = 0.04. Headache was the only frequent side effect of serotonin antagonists (30% incidence). All three serotonin antagonists sufficiently controlled nausea and vomiting during high-dose chemotherapy (BEAM) administration in 67-87% of patients. In comparison with ondansetron, both tropisetron and granisetron proved to be more effective after ASCT, when emetogenic factors other than chemotherapy alone participated.

Topics: Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cytarabine; Etoposide; Female; Granisetron; Hematopoietic Stem Cell Transplantation; Humans; Indoles; Lymphoma; Male; Melphalan; Nausea; Ondansetron; Serotonin Antagonists; Transplantation, Autologous; Tropisetron; Vomiting

Topics: Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Granisetron; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppression Therapy; Indoles; Leukemia; Male; Multiple Myeloma; Myelodysplastic Syndromes; Nausea; Ondansetron; Transplantation, Autologous; Transplantation, Homologous; Tropisetron; Vomiting

In this randomized study, the efficacy of a single dose of three serotonin antagonists were compared in prophylaxis of acute and delayed vomiting induced by moderately emetogenic, single-day chemotherapy in chemotherapy-naïve patients. A total of 54 patients were entered. Eighteen patients received ondansetron, 17 received tropisetron, and 19 received granisetron. Antiemetics were administered as 15-minute intravenous infusion before chemotherapy. Complete control of acute vomiting was achieved in 38.8% with ondansetron, 58.8% with tropisetron, and 73.7% with granisetron. Major response rates were 83.3%, 82.3%, and 89.5%, respectively. For the delayed control of emesis, complete control of delayed vomiting was achieved in 38.8% with ondansetron, 52.9% with tropisetron, and 73.7% with granisetron. The major response rates were 71.8%, 70.5%, and 100%, respectively. The adverse effects were rare and mild in all groups. The authors conclude that there may be clinically important differences among serotonin antagonists used for chemotherapy-induced emesis.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Female; Granisetron; Humans; Indoles; Male; Middle Aged; Ondansetron; Prospective Studies; Serotonin Antagonists; Tropisetron; Vomiting

Several studies have confirmed the efficacy of high-dose metoclopramide and, more recently, serotonin antagonists, with and without dexamethasone, in the prophylaxis of cisplatin-induced nausea and vomiting. Most of these trials have been reported from Western countries. There is little or no information about the efficacy and tolerability of these agents in ethnic groups in other countries. Furthermore, many patients in the developing countries cannot afford serotonin antagonists. The result is a critical need to evaluate these agents and justify their increasingly common use. The authors performed a prospective randomized trial to compare the efficacy and tolerability of tropisetron with and without dexamethasone against high-dose metoclopramide cocktail in patients receiving a uniform dose of cisplatin (100 mg/m2). Metoclopramide 2 mg/kg was combined with clemastine, dexamethasone, and lorazepam. These drugs were initially repeated at short intervals and subsequently given in the oral form for the next 5 days. Tropisetron 5 mg was administered intravenously 15 minutes immediately before cisplatin therapy and followed up with oral therapy for 5 days. The third group received the same doses of tropisetron along with dexamethasone before cisplatin and twice daily thereafter. The authors randomized 301 episodes. The patient characteristics were well balanced between the three groups. Acute nausea and vomiting were completely prevented in almost two thirds of patients receiving metoclopramide and tropisetron plus dexamethasone. These results are significantly superior to those of tropisetron alone (p < 0.01). Similarly, delayed nausea and vomiting were significantly better controlled with metoclopramdie cocktail and tropisetron plus dexamethasone than with tropisetron alone. Side effects were generally mild; however, they were more frequent with metoclopramide. The authors conclude that metoclopramide-based combination antiemetic therapy continues to be a cheaper alternative to serotonin antagonists and equally effective. Metoclopramide-based therapy, however, is more labor intensive, and issues related to administrative errors, side effects, and compliance gain increasing importance. The identification of persons at a higher risk for metoclopramide-induced side effects may help minimize the unacceptable consequences of therapy.

Topics: Acute Disease; Adult; Antiemetics; Antineoplastic Agents; Cisplatin; Dexamethasone; Drug Therapy, Combination; Female; Humans; Indoles; Male; Metoclopramide; Middle Aged; Nausea; Prospective Studies; Serotonin Antagonists; Tropisetron; Vomiting

The role of tropisetron as an anti-emetic drug in the prevention of delayed nausea and vomiting remains unclear. Therefore, effectiveness of tropisetron in patients receiving cancer chemotherapy was evaluated by application of summary measures using a quality of life (QOL) questionnaire. The diary-type QOL self-rating questionnaire was constituted by seven scales. A double-blind randomized, multicentre study was performed in 33 hospitals. Quality of life was measured in 98 patients. Patients receiving cisplatin were randomized to group T (administration of tropisetron before and 4 days after cisplatin treatment) and group P (administration of tropisetron before cisplatin treatment and followed by placebo for 4 days). The rate of complete protection from delayed emesis in the groups T and P was 46.3 and 36.5%. All scales, except social wellbeing changed immediately in both groups and reached a nadir on days 2-3, after that returning to the control levels during 2 weeks after cisplatin treatment. Group T was significantly better than group P in physical wellbeing, mental wellbeing, functional wellbeing and global QOL scores summarized by area under the curve and Difmax (maximum differences of QOL scales' score from the best score throughout the entire period). These results indicate that continuous administration of tropisetron could contribute to preventing patient QOL influenced by cisplatin treatment, and the combined use of summary measures may be useful for the evaluation of QOL in cancer clinical trial.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Cisplatin; Double-Blind Method; Female; Humans; Indoles; Male; Middle Aged; Nausea; Quality of Life; Surveys and Questionnaires; Tropisetron; Vomiting

The efficacy and tolerability of tropisetron alone or in combination with dexamethasone was studied in an open randomised trial in a total of 30 patients undergoing cisplatin based chemotherapy. Patients received tropisetron 5 mg plus dexamethasone 8 mg i.v. on day 1 followed by tropisetron 5 mg p.o. plus dexamethasone 4 mg orally bid on day 2-6 (group I) versus tropisetron 5 mg p.o. alone on day 2-6 (group II). No demographic difference among the groups was observed. Tumor locations were mainly at cervix (23%) and ovary (17%). Acute emesis was prevented completely, defined as no nausea and no vomiting, in 75 per cent of patients in group 1 compared with 73 per cent in group II. Delayed emesis was completely prevented in significantly more patients in group I (81% versus 49%). Adverse events were mild and similar in both groups. The most frequent side effects were headache, stupor and diarrhea. In conclusion, tropisetron is an effective and well tolerated antiemetic for preventing acute and delayed emesis in cisplatin-based chemotherapy. In addition, combining dexamethasone improved the efficacy in particular in controlling delayed emesis.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Dexamethasone; Drug Therapy, Combination; Female; Humans; Indoles; Male; Middle Aged; Nausea; Tropisetron; Vomiting

Tropisetron can prevent postoperative nausea and vomiting (PONV) at doses smaller than those used to control chemotherapy-induced nausea and vomiting. In this placebo-controlled study, the efficacy and tolerability of three different doses of tropisetron were compared for the treatment of established PONV after surgical procedures in general anesthesia. Of 1513 patients who satisfied inclusion criteria, 314 experiencing PONV during the first 2 h after recovery from anesthesia were treated with one of three different doses of tropisetron (0.5, 2, or 5 mg) or placebo, administered i.v. as a single dose. Patients were then observed during 24 h for efficacy and tolerability. All three doses of tropisetron were significantly better than placebo in controlling emetic episodes and in reducing the need for rescue treatment. There were no significant differences among the three doses. However, in the subgroup of patients who had previous PONV, and in those randomized for nausea alone, the 2-mg and 5-mg doses controlled emetic episodes better than the 0.5-mg dose. All studied doses of tropisetron were well tolerated and did not affect vital signs. We conclude that a single i.v. administration of tropiestron significantly reduces the recurrence of emetic episodes in patients with established PONV after elective surgery with general anesthesia. Its optimal dose seems to be 2 mg.. Three hundred-fourteen patients suffering from postoperative nausea and vomiting received different i.v. doses of a new antiemetic drug, tropisetron, to determine the lowest effective dose. We found that a single i.v. administration of tropisetron significantly reduced postoperative nausea and vomiting after elective surgery with general anesthesia.

Topics: Abdomen; Age Factors; Anesthesia, General; Antiemetics; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Indoles; Male; Narcotics; Nausea; Postoperative Period; Prognosis; Serotonin Antagonists; Tropisetron; Vomiting

The anti-emetic efficacy of a combination of tropisetron and dexamethasone was studied in 33 patients who underwent bone marrow transplantation. Another 50 patients receiving conventional anti-emetic therapies in bone marrow transplantation served as control. On the first and second days of preconditioning chemotherapy, 51% and 36% respectively of patients in the tropisetron and dexamethasone group did not experience vomiting, compared with only 12% and 10% of control group patients (P < 0.001). The mean number of episodes of vomiting in the tropisetron and dexamethasone group was also significantly lower than in the control group (0.97+/-1.65 vs 3.50+/-2.45 and 1.30+/-1.40 vs 4.44+/-2.91 respectively, both P < 0.001). Control of vomiting in the two groups was not significantly different during days 3-6. Analysis of patients receiving busulfan and cyclophosphamide as the preconditioning regimen still showed better anti-emetic control in the tropisetron and dexamethasone group than in the control group on the first two days of treatment (total control rate 33.3% vs 6.5% and 44.4% vs 12.9% respectively, P < 0.001). Patients given tropisetron and dexamethasone combination more frequently suffered from dizziness and burning sensation of the chest. However, diarrhea and extrapyramidal symptoms were the most frequent adverse effects seen after using conventional anti-emetic combination. The combination of tropisetron and dexamethasone was thus superior to conventional anti-emetic combinations in preventing vomiting during preconditioning period of bone marrow transplantation. The adverse effects of this combination were minimal and well tolerated by patients.

Topics: Adolescent; Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Busulfan; Carmustine; Child; Cyclophosphamide; Cytarabine; Dexamethasone; Dizziness; Drug Therapy, Combination; Female; Headache; Heartburn; Humans; Indoles; Leukemia; Male; Melphalan; Middle Aged; Multiple Myeloma; Podophyllotoxin; Transplantation Conditioning; Tropisetron; Vomiting; Whole-Body Irradiation

The single-institution, prospective, randomized trial was performed to evaluate the efficacy of tropisetron and chlorpromazine in the management of nausea and vomiting of terminal cancer patients. Patients had no recent chemotherapy or radiotherapy, and emesis was not due to bowel obstruction, electrolytic or metabolic disturbances, drug intake, or intracranial disease. One hundred and sixty patients randomly received either (a) chlorpromazine (CLO) (50 mg/day) plus dexamethasone (DEX) (2 mg/day), (b) chlorpromazine (25 mg/day) plus tropisetron (TRO) (5 mg/day), (c) chlorpromazine (25 mg/day plus tropisetron (5 mg/day) plus dexamethasone (2 mg/day), or (d) tropisetron (TRO) (5 mg/day). Patients were monitored from day 1 to day 15. No nausea or vomiting was defined as "total" control. On day 15, total vomiting control was achieved in 33.3% of the patients receiving CLO + DEX, 84.6% of the patients receiving CLO + TRO, 92.5% of the patients receiving CLO + TRO + DEX, and 78.9% of the patients receiving TRO. Total control of nausea was achieved in 18.0% of the patients receiving CLO + DEX, 74.4% of the patients receiving (CLO + TRO), 85.0% of the patients receiving CLO + TRO + DEX, and 65.8% of the patients receiving TRO. Tropisetron-containing combinations produced significant control of nausea and vomiting from the third day onward. All antiemetic drugs were well tolerated. These data suggest that tropisetron-containing combinations or tropisetron as a single agent are much more effective in the control of emesis in patients with advanced cancer than the conventional antiemetic combination of chlorpromazine plus dexamethasone. Tropisetron is well tolerated and may be the best choice for controlling persistent nausea and vomiting in terminal cancer patients.

Topics: Adult; Aged; Antiemetics; Chlorpromazine; Drug Therapy, Combination; Female; Humans; Indoles; Male; Middle Aged; Nausea; Neoplasms; Serotonin Antagonists; Tropisetron; Vomiting

In a randomised, double-blind and parallel-design multicentre study, 282 chemotherapy-naive cancer patients received tropisetron 5 mg intravenously (i.v.) before high-dose cisplatin on day 1, and oral tropisetron 5 mg daily on days 2-6, in combination with either placebo (n = 143) or dexamethasone (n = 135), given i.v. on day 1 and orally on days 2-6. Complete protection from acute vomiting/nausea was achieved in 76.3%/79.3% of patients receiving the combination and in 55.2%/61.5% of those receiving tropisetron alone. Complete protection on days 2-6 from delayed vomiting/nausea was obtained in 60%/60% and 39.2%/40.6%, respectively. Tropisetron in combination with dexamethasone is safe and more effective than tropisetron alone in the prevention of both acute and delayed cisplatin-induced emesis.

Topics: Administration, Oral; Adult; Aged; Antiemetics; Antineoplastic Agents; Cisplatin; Dexamethasone; Double-Blind Method; Drug Combinations; Female; Humans; Indoles; Infusions, Intravenous; Male; Middle Aged; Nausea; Treatment Outcome; Tropisetron; Vomiting

Chemotherapy-induced emesis is one of the most disturbing side effects of cancer therapy. Control of acute emesis has improved substantially during recent years, but control of delayed emesis and nausea remains a challenging problem. The role of 5-HT3 receptor antagonists in the treatment of delayed emesis is disputed.. Tropisetron, a highly specific 5-HT3 receptor antagonist, was compared (as an adjunct to dexamethasone) with placebo in a randomized, double blind, multicenter trial for the prevention of delayed emesis during platinum-containing chemotherapy. Three hundred chemotherapy-naive women with gynecologic malignancies were included. The cisplatin dose was in the range of 50-100 mg/m2.. Acute emesis was prevented completely in 87% of patients and acute nausea in 77% of patients in the complete series. During the complete delayed period (Days 2-6), total control of emesis was achieved in 77% of the dexamethasone and tropisetron-treated patients and in 72% of the patients receiving dexamethasone and placebo (P = 0.2473). During the same period nausea was controlled completely in 42% of the dexamethasone and tropisetron group and in 41% of the dexamethasone and placebo group. On Day 3, complete protection from nausea was achieved in 65% of patients receiving tropisetron and in 51% of patients receiving placebo (P = 0.0304). Constipation occurred more frequently in the tropisetron group.. Tropisetron added to dexamethasone improved control of delayed nausea on Day 3 compared with placebo. No significant differences were recorded regarding control of delayed emesis.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cisplatin; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Drug Tolerance; Female; Genital Neoplasms, Female; Humans; Indoles; Middle Aged; Nausea; Serotonin Antagonists; Time Factors; Tropisetron; Vomiting

A single institution, prospective, randomized trial was performed in terminal cancer patients to compare tropisetron (TRO), metoclopramide (MET), and chlorpromazine (CHL) in the management of nausea and emesis. Patients had far advanced cancer, were far removed from chemotherapy or radiotherapy, and their nausea and emesis was not due to bowel obstruction, drug intake, or cranial, electrolytic, or metabolic causes. The effects of antiemetic treatments were evaluated from Days 1-15.. Two hundred and eighty patients were randomized to receive 1) MET+ dexamethasone (DEX) (10 mg*4 and 2 mg*1, respectively, orally), 2) TRO (5 mg*1, orally), 3) TRO + MET (5 mg*1 and 10 mg*2, respectively, orally), 4) TRO + MET + DEX (5 mg*1, 10 mg*2, and 2 mg*1, respectively, orally), 5) CHL + DEX (25 mg*2 and 2 mg*1, respectively, orally), 6) TRO + CHL (5 mg*1 and 12.5 mg*2, respectively, orally), or 7) TRO + CHL + DEX (5 mg*1, 12.5 mg*2, and 2 mg*1, respectively, orally). Total control was defined as no nausea or emesis.. By the end of the 15th day, total control of emesis was obtained in 23.6% (9 of 38) of MET + DEX patients, 78.9% (30 of 38) of TRO patients, 84.2% (32 of 38) of TRO + MET patients, 92.3% (36 of 39) of TRO + MET + DEX patients, 33.3 (13 of 39) of CHL + DEX patients, 84.6% (33 of 39) of TRO + CHL patients, and 92.5% (37 of 40) of TRO + CHL + DEX patients. Total control of nausea was achieved in 18.4% (7 of 38) of MET + DEX patients, 65.7% (25 of 38) of TRO patients, 73.6% (28 of 38) of TRO + MET patients, 87.1% (34 of 39) of TRO + MET + DEX patients, 17.9% (7 of 39) of CHL + DEX patients, 74.3% (29 of 39) of TRO + CHL patients, and 85% (34 of 40) of TRO + CHL + DEX patients. When comparing MET + DEX versus TRO; MET + DEX versus TRO + MET; MET + DEX versus TRO + MET + DEX; MET + DEX versus TRO + CHL; MET + DEX versus TRO + CHL + DEX; CHL + DEX versus TRO; CHL + DEX versus TRO + MET; CHL + DEX versus TRO + MET + DEX; CHL + DEX versus TRO + CHL; and CHL + DEX versus TRO + CHL + DEX, significant differences were noted. All antiemetic drugs were well tolerated with no severe side effects observed in any treatment arm.. These data suggest that 5-HT3 receptor antagonists such as tropisetron clinically are more effective in the control of emesis of patients with far advanced cancer than previously used agents. This study raises important issues when attempting to decide which antiemetic therapy to choose for an individual patient with far advanced disease.

Topics: Adult; Aged; Antiemetics; Chlorpromazine; Dexamethasone; Drug Therapy, Combination; Female; Humans; Indoles; Male; Metoclopramide; Middle Aged; Nausea; Neoplasms; Prospective Studies; Tropisetron; Vomiting

In this randomized, double-blind, placebo-controlled study, we compared the efficacy of tropisetron 5 mg with tropisetron 2 mg for the prevention of postoperative nausea and vomiting (PONV) after breast surgery. One hundred forty-eight female patients were randomized to receive either tropisetron 5 mg (n = 49), tropisetron 2 mg (n = 49), or saline (n = 50) before the induction of anesthesia with thiopental and morphine. Anesthesia was maintained with nitrous oxide and isoflurane. Postoperative analgesia was provided by patient-controlled analgesia with i.v. morphine. The incidence of PONV, the pain score, and the analgesic requirement were recorded for 48 h. There was no difference among groups in patient characteristics, risk factors for PONV, morphine consumption, or side effects. During the first 6 h postoperatively, the incidence of PONV after tropisetron 2 mg and 5 mg were similar and were superior to placebo (P < 0.001). After 6 h, the incidence of PONV increased significantly in patients who had received tropisetron 2 mg (P = 0.01) and was greater than that in patients who had received tropisetron 5 mg (P = 0.001). We conclude that single-dose tropisetron 5 mg is more effective than tropisetron 2 mg in the prevention of PONV after breast surgery.. Breast surgery is associated with a high incidence of postoperative nausea and vomiting. A single dose of i.v. tropisetron 5 mg is well tolerated and decreases the number of vomiting and nausea episodes after surgery.

Topics: Adolescent; Adult; Aged; Analgesia, Patient-Controlled; Antiemetics; Double-Blind Method; Female; Humans; Indoles; Mastectomy, Modified Radical; Mastectomy, Segmental; Middle Aged; Nausea; Pain, Postoperative; Postoperative Complications; Tropisetron; Vomiting

Nausea and vomiting are common after adenotonsillectomy. Tropisetron is a new, long-acting serotonin antagonist that is an effective antiemetic in adults. Its effect on postoperative nausea and vomiting in children is unknown. We carried out a randomized, double-blind study of the effects of a single i.v. dose of tropisetron on vomiting after tonsillectomy with or without adenoidectomy in children. Forty-eight children undergoing tonsillectomy or adenotonsillectomy received at induction of anaesthesia either tropisetron 0.1 mg kg-1 or placebo. The incidence of vomiting was recorded for the first 24 h after surgery by nursing staff and then by parents after discharge from hospital. Children received metoclopramide 0.15 mg kg-1 as a rescue antiemetic. We found that tropisetron reduced the overall incidence of emetic episodes after surgery (29% compared with 65% in control group; P = 0.019) and the incidence of severe vomiting (0% compared with 52% in control group; P < 0.001). We conclude that tropisetron is an effective antiemetic for children undergoing tonsillectomy.

Topics: Adenoidectomy; Antiemetics; Child; Child, Preschool; Double-Blind Method; Female; Humans; Indoles; Male; Postoperative Complications; Serotonin Antagonists; Tonsillectomy; Tropisetron; Vomiting

Tropisetron (Navoban") suppresses nausea and vomiting induced by cancer chemotherapy by antagonizing central and peripheral 5-HT3 receptors. In this open-label study, tropisetron was evaluated in 873 patients who were either refractory to antiemetic treatment during previous chemotherapy or at high risk of emesis as a result of current chemotherapy. The most commonly used agents alone or in combination were cyclophosphamide (35%), fluorouracil (30%), carboplatin (24%) and cisplatin (21%). The primary tumors were breast cancer (27%), lung cancer (16%), gynecological cancers (12%) and lymphoma (9%). Tropisetron was administered as a 15 min infusion prior to chemotherapy and an additional oral 5 mg dose was taken by 80% of the patients on subsequent days. During course 1, complete response to tropisetron was obtained in 64% of patients on day 1, 54% on day 2, 63% on day 3, 71% on day 4 and 77% on day 5. Very similar response rates were found for the six chemotherapy courses. There were few failures after complete and partial response, at maximum 3 and 15%, respectively. Moreover, 24-38% of those with partial response and 7-29% of those with failure could achieve a complete response during the following cycle. The treatment was well tolerated, the most frequently reported adverse events being constipation (3.7%) and headache (2.6%).

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Female; Humans; Indoles; Male; Middle Aged; Nausea; Neoplasms; Prospective Studies; Serotonin Antagonists; Tropisetron; Vomiting

This study was performed to compare the efficacy of tropisetron, droperidol, and saline in the prevention of postoperative nausea and vomiting (PONV) and to compare the possible adverse effects of these drugs in gynecologic incontinence surgery. Using a randomized, double-blind study design, we studied 150 women undergoing gynecologic incontinence surgery with standardized general anesthesia. At the end of surgery, the patients received either tropisetron 5 mg, droperidol 1.25 mg, or 0.9% saline intravenously (i.v.). As a rescue antiemetic, the patients received metoclopramide 10 mg i.v.. The episodes of nausea, retching, and vomiting; the need for rescue treatment; and the type and severity of adverse events were recorded at four occasions during the 48-h observation period. Pain, anxiety, drowsiness, and general satisfaction were also evaluated on a linear numerical scale of 0-10. Complete response (no PONV within the 48-h observation period) occurred similarly in the study groups (tropisetron 25%, droperidol 22%, and placebo 18%). Tropisetron and droperidol had no effect on the incidence of nausea and retching. However, the incidence of vomiting was significantly less in the tropisetron group than in the placebo group (tropisetron 19%, droperidol 45%, and placebo 57%). The number of emetic episodes (retching and/or vomiting) per patient within 48 h was significantly decreased under tropisetron when compared with placebo (tropisetron 2.5 +/- 3.4, droperidol 4.2 +/- 6.1, placebo 5.9 +/- 7.1). With regard to adverse events, the patients in the droperidol group had significantly more anxiety than the placebo group (2-6 h postoperatively), more drowsiness than the tropisetron and placebo groups (0-2 h postoperatively), and more dissatisfaction than the tropisetron (0-6 h postoperatively) and placebo groups (2-6 h postoperatively). We conclude that tropisetron given 5 mg i.v. during anesthesia in gynecologic incontinence surgery effectively prevents vomiting but not nausea and retching, while 1.25 mg i.v. droperidol fails to prevent any of these emetic symptoms and results in adverse events.

Topics: Antiemetics; Double-Blind Method; Droperidol; Female; Genital Diseases, Female; Humans; Indoles; Middle Aged; Nausea; Postoperative Complications; Sodium Chloride; Tropisetron; Vomiting

There is still controversy as to what constitutes the optimal therapy for acute and delayed chemotherapy-induced emesis and nausea. We conducted a three-armed randomized multi-centre study in 193 chemotherapy-naive patients receiving highly emetogenic chemotherapy inducing both acute and delayed symptoms (cisplatin > or = 50 mg/m2, carboplatin > or = 300 mg/m2, cyclophosphamide > or = 750 mg/m2, ifosfamide > or = 1.5 g/m2 on day 1). Group A: 1 x 5 mg tropisetron i.v. on day 1 + 2, then 10 mg p.o. (oral dose now recommended: 5 mg); group B: tropisetron as for A+dexamethasone, 20 mg i.v., on days 1 + 2, then 4 mg i.v./p.o.; group C: tropisetron as for A+metoclopramide, 20 mg i.v. +2 x 10 mg p.o. on day 1, then 3 x 10 mg p.o. Treatment was continued for at least 2 days after the end of chemotherapy. Tropisetron+dexamethasone was significantly superior to tropisetron alone both for acute (P = 0.0064) and delayed (P = 0.0053) emesis. Complete control of acute and delayed emesis (nausea) was achieved in 80% (75%) and 53% (46%) in group A, 97% (90%) and 80% (58%) in group B, and 86% (80%) and 49% (45%) in group C. Patients completely asymptomatic during the whole cycle accounted for 26% of those in group A, 49% in group B and 28% in group C. The most frequent adverse events were constipation (16.6%), headache (7.3%) and tiredness (7.3%). Once-daily tropisetron+dexamethasone over several days is well tolerated and is a simple means of achieving further significant improvement in the efficacy of tropisetron against acute and delayed symptoms.

Topics: Acute Disease; Adult; Aged; Antiemetics; Antineoplastic Agents; Dexamethasone; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Indoles; Male; Metoclopramide; Middle Aged; Nausea; Quality of Life; Treatment Outcome; Tropisetron; Vomiting

Nausea and vomiting are frequent side effects during adjuvant abdominal radiotherapy in seminoma stage I patients. This study evaluates the efficacy and side effects of prophylactically administered tropisetron in comparison to metoclopramide.. Twenty-three seminoma stage I patients who were to undergo adjuvant abdominal radiotherapy (30 Gy) were included in a prospective, randomised, open study. The patients were allocated to receive adjuvant daily tropisetron 5 mg p.o. (TROP group) (11 patients) or metoclopramide 30 mg p.o. (MET group) (12 patients), allowing an eventual dose increase to 60 mg. Evaluation was based on diary cards filled in by the patients during the treatment period. Nausea, vomiting, abdominal pain and bowel motions were assessed.. Nausea was significantly lower in the TROP group as compared with the MET group (median: 0.14 vs. 1.32; P = 0.03). Thirty percent of all patients experienced vomiting. In the TROP group one patient had a mean number of emetic events > 0 as compared with 6 patients in the MET group (P = 0.07). Two patients in the TROP group and one in the MET group discontinued therapy due to lacking control of emesis. In two further patients the doubling of the metoclopramide resulted in acceptable control of nausea/vomiting. Both drugs were generally well tolerated.. Seminoma stage I patients on tropisetron experienced less nausea and vomiting during abdominal radiotherapy than patients receiving metoclopramide. The costs of the former drug may, however, not justify its use as first choice anti-emetic since few patients in either group experienced severe nausea.

Topics: Adult; Antiemetics; Dose-Response Relationship, Drug; Humans; Indoles; Male; Metoclopramide; Nausea; Neoplasm Staging; Prospective Studies; Radiotherapy, Adjuvant; Seminoma; Testicular Neoplasms; Treatment Outcome; Tropisetron; Vomiting

Cisplatin-induced emesis is one of the most feared side effects in cancer treatment. High-dose metoclopramide may prevent only 30-40% of cases of acute emesis. Investigations to test the efficacy of new antiemetics are mandatory. We compared the efficacy, toxicity, and patients' preference for tropisetron, a new 5-hydroxytryptamine3 (HT3) receptor antagonist, with those of a combination of high-dose metoclopramide, dexamethasone, diphenhydramine, and lorazepam (metoclopramide cocktail) in a randomized crossover study for the control of nausea and vomiting during cisplatin-containing chemotherapy. A total of 62 chemotherapy-naive women were included and followed over 3 consecutive courses. Detailed analysis comparing the incidence of acute emesis for each 4 h period following cisplatin infusion was also performed. Complete protection from acute emesis was obtained in 48% of patients receiving tropisetron and 29% of patients receiving the metoclopramide cocktail over the first two courses of chemotherapy (P = 0.029). When the frequency of acute emesis in all patients was compared on a daily basis, no significant difference was found. When emesis frequency was compared over each 4 h period following infusion of cisplatin, tropisetron was superior to the metoclopramide cocktail during the first, the second, and the first and second periods (P = 0.0001, P = 0.01 and P = 0.0006, respectively). This superiority reversed after 12 h but did not reach statistical significance (P = 0.112). Tropisetron was more effective in controlling acute nausea, but metoclopramide provided better control of delayed emesis. A drop in efficacy over successive courses was observed in patients receiving metoclopramide first but was not seen in tropisetron-first patients. A tendency for tropisetron preference was observed. Tropisetron is more effective than the metoclopramide cocktail in the control of chemotherapy-induced vomiting within 8 h of the implementation of cisplatin and in the control of nausea on the 1st day. To improve the control of chemotherapy-induced emesis, further investigations on the additional tropisetron dosing at 8 h after cisplatin infusion or the combination use of tropisetron and other antiemetics by a continuous 4 h period of observation and comparison are mandatory.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Cisplatin; Cross-Over Studies; Drug Therapy, Combination; Female; Genital Neoplasms, Female; Humans; Indoles; Metoclopramide; Middle Aged; Nausea; Severity of Illness Index; Time Factors; Tropisetron; Vomiting

The aim of this study was to evaluate the efficacy of tropisetron, a selective 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, versus placebo in the prevention of postoperative nausea and vomiting in patients undergoing general anesthesia for gynecologic surgery. Ten minutes before induction of general anesthesia, 80 patients received in a double-blind manner a single intravenous (IV) injection of either 5 mg tropisetron or a matching placebo. Anesthesia was induced with thiopental and maintained with nitrous oxide and enflurane in oxygen. In the first 24 h postoperatively 7 of 40 patients (17.5%) given tropisetron and 16 of 40 patients (40%) receiving placebo vomited (P < 0.05). The incidence of nausea was 30% (12/40) in the tropisetron group and 52% (21/40) in the placebo group (P < 0.05). A total effective antiemetic response showed 26 patients (65%) in the tropisetron group and 16 patients (40%) in the placebo group (P < 0.05). We conclude that tropisetron given IV prior to gynecologic procedures in general anesthesia significantly reduces postoperative nausea and vomiting when compared to placebo without causing any adverse effect.

Topics: Adolescent; Adult; Aged; Antiemetics; Double-Blind Method; Female; Genitalia, Female; Humans; Indoles; Middle Aged; Nausea; Postoperative Complications; Premedication; Serotonin Antagonists; Tropisetron; Vomiting

(i) To assess the efficacy and tolerability of tropisetron when used for acute and delayed cisplatin-induced emesis. (ii) To investigate whether dexamethasone added to tropisetron improves the control of emesis for patients who do not achieve a complete response to tropisetron alone. (iii) To assess sex of the patient and alcohol intake as prognostic factors for nausea and vomiting.. A prospective open label phase II trial over one or two cycles of chemotherapy. Data collection was based on observed response and patients' self-reporting.. Twenty Australian tertiary care hospitals in 1994.. 102 male and female patients from 18 to 75 years with histologically confirmed malignancy receiving their first chemotherapy containing > or = 50 mg/m2 cisplatin.. In Cycle 1 tropisetron 5 mg was given intravenously before chemotherapy on Day 1, then 5 mg orally before breakfast on Days 2 to 6. In Cycle 2, dexamethasone 20 mg intravenously on Day 1, then 8 mg orally on Days 2 to 6 could be added to tropisetron if a complete antiemetic response had not been achieved in Cycle 1.. Number of vomiting episodes and severity of nausea for 6 days after chemotherapy; severity of side effects; patient satisfaction with chemotherapy treatment; oestradiol levels in women; and past alcohol consumption in men and women.. (i) The complete response rate (CR) for acute emesis in Cycle 1 was 64% (95% confidence interval [CI], 54%-72%), with 84% (95% CI, 76%-90%) having < or = 2 vomits. The CR for delayed emesis was 24% (95% CI, 17%-32%). The CR for acute nausea was 56% (95% CI, 47%-66%), with 97% (95% CI, 91%-99%) having < or = 2 nausea episodes. The CR for delayed nausea was 21% (95% CI, 14%-30%). Seventy-one patients received Cycle 2. The main side effects were headache (20 patients) and constipation (16 patients). The control of acute emesis was rated as "good" or "very good" by 68% of investigators; 85% rated the tolerability of treatment as "good" or "very good". Treatment was rated as "very satisfactory" or "satisfactory" by 52% of patients. (ii) The CR for acute emesis with dexamethasone added was 78% (95% CI, 64%-88%). (iii) Women with lower oestradiol levels had better control of emesis, although this difference was not statistically significant. Chronic alcohol intake and binge drinking were strongly associated with a complete acute antiemetic response.. Tropisetron was effective for acute cisplatin-induced emesis; adding dexamethasone enhanced this response. Both single and combined therapy had less effect on delayed emesis. The impact of alcohol on control of emesis is a chronic rather than acute phenomenon which requires prospective testing.

Topics: Adolescent; Adult; Aged; Alcohol Drinking; Antiemetics; Antineoplastic Agents; Cisplatin; Dexamethasone; Estradiol; Female; Humans; Indoles; Male; Middle Aged; Nausea; Neoplasms; Prospective Studies; Treatment Outcome; Tropisetron; Vomiting

A single-institution, prospective, randomized, open controlled trial was carried out on head and neck cancer patients to compare granisetron (GRA), ondansetron (OND), and tropisetron (TRO) in the prevention of cisplatin-induced acute nausea and vomiting. All patients were chemotherapy-naive and treated with cisplatin on Day 1 (80 to 100 mg/m2).. One hundred seventeen patients were treated for a total of 463 cycles of cisplatin-based chemotherapy and randomized to receive 24 mg of OND intravenously (i.v.), 3 mg of GRA i.v., or 5 mg of TRO i.v. for the control of acute nausea and emesis.. In the GRA group, complete response (CR) was obtained in 119 of 165 cycles (72.1%), major response (MR) in 32 cycles (19.4%), minor response (MiR) in 5 cycles (3%), and a failure (F) in 9 cycles (5.5%). In the OND group, CR was obtained in 110 of 150 cycles (73.3%), MR in 31 cycles (20.7%), MiR in 2 cycles (1.3%), and F in 7 cycles (4.7%). In the TRO group, CR was obtained in 100 of 148 cycles (67.6%), MR in 26 cycles (17.6%), MiR in 15 cycles (10.1%), and F in 7 cycles (4.7%). Major efficacy (CR + MR) was obtained in 151 of 165 cycles (91.5%) for GRA, in 141 of 150 cycles (94.0%) for OND, and in 126 of 148 cycles (85.2%) for TRO. The difference in major efficacy between OND and TRO was statistically significant. When comparing MiR, both GRA and OND were more effective than TRO. No other significant differences were observed among the three antiemetic agents.. Although our results were achieved in an open trial, they show that GRA and OND are equally effective antiemetic agents in the prevention of cisplatin induced acute nausea and vomiting. TRO provides almost the same protection but is not as effective as OND for major efficacy. All three antiemetics can be administered safely to patients undergoing chemotherapy with cisplatin at doses of 80 mg/m2 or more.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Cisplatin; Drug Administration Schedule; Female; Granisetron; Head and Neck Neoplasms; Humans; Indoles; Male; Middle Aged; Nausea; Ondansetron; Prospective Studies; Serotonin Antagonists; Tropisetron; Vomiting

A new questionnaire on QOL of patients with chemotherapy-induced emesis and vomiting was developed, and its reliability and validity were investigated in the present multi-center clinical trial. The questionnaire consisted of 15 items which included descriptive questions on appetite, feeling, sleep, mental fatigue, anxiety, pain, sputum, respiratory distress, nausea, vomiting, abdominal condition, daily life in a hospital and relationship with family, a linear analogue scale representing influence of nausea and vomiting on patient's life during 24 hours, and a face scale as the global scale. Data from 98 patients with cancer were analyzed by principal component analysis and correlation analysis. The results were summarized as follows: 1) Recollect rate was 78.1% and complete response rate was 86.0% in this QOL measurement. 2) A clear correlation was observed between appetite, feeling, nausea, vomiting and the physiological scale, between sleep, mental fatigue, anxiety, pain, abdominal condition and the psychological scale, between sputum, respiratory distress and the respiratory condition related scale, between daily life in hospital and the active scale, between relationship with family and the social relation scale. These results satisfied internal consistency. 3) As for test-retest reliability, the total score of 13 descriptive items between the day before and two days before the start of chemotherapy showed no significant difference. 4) The 13 items were grouped into physiological, the psychological, the respiratory condition related, the active and the social relation scales, and these scales belonged to a different dimension. 5) The linear analogue scale, the face scale and the total scores of 13 descriptive items correlated respectively with all of items except item of, relationship with family. 6) As for concurrent validity, vomiting frequency, severity of nausea and anorexia correlated with the physiological scale. Severity of nausea and anorexia also correlated with the psychological and active scales. 7) As a result of investigation of sensitivity, the total score of the 13 descriptive items, the linear analogue scale representing influence of nausea and vomiting on patient's life during 24 hours and the face scale revealed the poorest levels 2-3 days after chemotherapy but recovered thereafter. The aggravation of QOL of patients treated with chemotherapy was reduced in the anti-emetic administration group compared with the placebo administrati

Topics: Aged; Anorexia; Antiemetics; Antineoplastic Agents; Double-Blind Method; Female; Humans; Indoles; Japan; Male; Middle Aged; Nausea; Quality of Life; Reproducibility of Results; Sensitivity and Specificity; Surveys and Questionnaires; Tropisetron; Vomiting

We have reported our "new questionnaire of QOL (quality of life) in anti-emetic therapies during cancer chemotherapy" and demonstrated its reliability and validity. In the present study we investigated the utility of tropisetron capsules for delayed nausea and vomiting induced by cancer chemotherapies with CDDP single administration in a placebo-controlled double-blind comparative study using the questionnaire. The questionnaire was composed of the following scales: a physiological scale (appetite, feeling, vomiting, nausea), a psychological scale (sleep, mental fatigue, anxiety, pain, abdominal condition), a respiratory condition related scale (sputum, respiratory distress), an active scale (daily life in a hospital), a social relation scale (understanding of the family), a linear analogue scale for evaluation of the influence of nausea and vomiting in patient's life during 24 hours, and a face scale as the global scale. First, all patients were administered a preventive dose of tropisetron capsule on day 1 (the day of CDDP administration) and then allotted to once-daily oral administration of either a tropisetron (T group) or a placebo (P group) capsule during days 2 to 5 by a double-blind method. Chronological changes of QOL during the study period were measured by the area under the curve (AUC) generally used for calculation of blood levels of drugs. The maximum fluctuation (Difmax) of QOL scores throughout the whole study period was also evaluated. The data were collected from 114 cases, and 98 cases (51 in P group, 47 in T group) were analyzed. 1) The total score or 13 items (a modified linear analogue scale with 5 graduations), the face scale and linear analogue scale of T group were higher (better) than those of P group. 2) As for the total score of each scale, the physiological, psychological and active scales in the T group showed higher (better) levels than the P group. 3) As for the AUC values, the T group was lower (better) than the P group in most items. In AUC of the total score of 13 items, the face scale, the physiological and the psychological scales, the T group was significantly superior to the P group. 4) AUC levels of each item belonged to the physiological and the psychological scales in the T group tended to be lower (better) than the P group, and "sleep" and "pain" in the psychological scale were significantly lower (better) in T group than P group. 5) In Difmax values, all scales except respiratory condition related scale showed

Topics: Adolescent; Adult; Aged; Antiemetics; Capsules; Cisplatin; Double-Blind Method; Female; Humans; Indoles; Japan; Male; Middle Aged; Nausea; Neoplasms; Quality of Life; Surveys and Questionnaires; Tropisetron; Vomiting

In a prospective, randomized, multicentre, double-blind, placebo-controlled study, we have compared the efficacy of a single i.v. dose of tropisetron 0.5 mg, 2 mg and 5 mg in the prevention of postoperative nausea and vomiting (PONV). We studied 385 ASA class I and II female patients undergoing abdominal or vaginal gynaecological surgery, including laparoscopy. Tropisetron or placebo were administered before a standardized general anaesthetic. The frequency of vomiting in the 24-h period after entry into the recovery room was reduced from 44% after placebo to 31%, 26% and 30% after tropisetron 0.5 mg, 2 mg and 5 mg, respectively (P = 0.06, P = 0.009 and P = 0.043; unadjusted). Compared with placebo, nausea was reduced from 55% to 46%, 34% and 46% (P = 0.25, P = 0.003, P = 0.22), and need for rescue treatment from 39% to 29%, 23% and 35% (P = 0.13, P = 0.017 and P = 0.59) for the same groups. Tropisetron 2 mg appeared to be the optimal dose for prophylaxis against PONV with a side-effect profile similar to that of placebo.

Topics: Adult; Aged; Anesthesia Recovery Period; Antiemetics; Double-Blind Method; Female; Genitalia, Female; Humans; Indoles; Injections, Intravenous; Middle Aged; Nausea; Postoperative Complications; Prospective Studies; Serotonin Antagonists; Tropisetron; Vomiting

One hundred and twenty patients undergoing elective ophthalmic surgery under general anaesthesia were investigated in a randomised, double-blind, parallel group study of postoperative nausea and vomiting. Patients received tropisetron 0.1 mg.kg-1, metoclopramide 0.25 mg.kg-1 or placebo given at the end of anaesthesia. In comparison with placebo, tropisetron significantly reduced the degree of nausea (p < 0.01), whereas metoclopramide reduced both nausea (p < 0.05) and vomiting (p < 0.05). There were no statistically significant differences between the two active agents in their efficacy to postoperative nausea and vomiting. The patients in the placebo group required rescue antiemesis more often in the postanaesthesia care unit. Our results suggest that tropisetron may not be suitable as a routine, primary therapy for the prevention of postoperative nausea and vomiting.

Topics: Adolescent; Adult; Aged; Anesthesia, General; Antiemetics; Double-Blind Method; Female; Humans; Indoles; Male; Metoclopramide; Middle Aged; Nausea; Ophthalmologic Surgical Procedures; Postoperative Complications; Tropisetron; Vomiting

1. We report a single-blind randomized crossover trial comparing the efficacy of tropisetron plus dexamethasone (TROPDEX) vs conventional combination of metoclopramide, dexamethasone and diphenhydramine (METDEX) in prevention of acute and delayed vomiting in Chinese patients receiving high dose cisplatin. 2. Thirty-six consecutive patients with nasopharyngeal carcinoma were entered into the study, all received cisplatin at a dose range of 60-100 mg/m2. Patients were randomized in the sequence of antiemetic regimens used in two consecutive cycles. 3. The TROPDEX regimen consisting of tropisetron 5 mg i.v. and dexamethasone 20 mg i.v. given on day 1 of chemotherapy, followed by oral maintenance with tropisetron 5 mg daily and dexamethasone 4 mg twice daily from day 2 to 6. The METDEX regimen consisting of metoclopramide 1 mg kg-1 i.v., dexamethasone 20 mg i.v. and diphenhydramine 25 mg i.v. given before chemotherapy and then 2 hourly for two more doses on day 1, followed by oral metoclopramide 20 mg 6 hourly from day 2 to 6. 4. Complete control of acute vomiting was observed in 64% of patients with TROPDEX as compared with 14% with METDEX (P < 0.01). While complete plus major control of acute vomiting was observed in 84% with TROPDEX as compared with 58% with METDEX. The mean vomiting episodes on day 1 were 1.4 with TROPDEX as compared with 3.5 with METDEX (P < 0.01). There was, however, no significant difference between the two regimens in the control of delayed vomiting. 5. When patients randomized to TROPDEX in the second cycle were compared with those with TROPDEX in the first cycle, the antiemetic efficacy was reduced, with mean acute vomiting episodes of 2 in the former compared with 0.8 in the latter (P < 0.01). 6. The most common adverse effect observed was headache in TROPDEX (27%) and dizziness in METDEX (40%). 7. In conclusion, the antiemetic regimen TROPDEX is effective in Chinese patients receiving high dose cisplatin chemotherapy and is well tolerated. It is better than conventional METDEX regimen in the control of acute vomiting, but not in the control of delayed vomiting.

Topics: Antiemetics; Antineoplastic Agents; Asian People; Cisplatin; Cross-Over Studies; Dexamethasone; Diphenhydramine; Drug Therapy, Combination; Female; Hong Kong; Humans; Indoles; Male; Metoclopramide; Middle Aged; Nasopharyngeal Neoplasms; Single-Blind Method; Tropisetron; Vomiting

While the use of 5-HT3 receptor antagonists is clearly justified in patients receiving cisplatin, their role with less emetic drugs is still not defined. The aim of our randomized study was to verify the efficacy of the single standard dose of three 5-HT3-receptor-antagonists in moderately emetic chemotherapies. Sixty chemotherapy-naive breast cancer patients of 30 to 71 years in age, P.S. = 0-1, receiving 5-fluorouracil-epirubicin-cyclophosphamide (FEC 75) q 21 days or cyclophosphamide-methotrexate-5-fluorouracil (CMF) or 120 mg/m2 epirubicin or high dose mitomycin-methotrexate-mitoxantrone (MMM) q 14 days (+ G-CSF) or 100 mg/m2 epirubicin (+ G-CSF) were randomized to receive, 15 min before chemotherapy, 8 mg i.v. bolus of ondansetron or 3 mg i.v. granisetron or 5 mg i.v. tropisetron and no further antiemetic therapy in the following days. 180 cycles were evaluable. Complete protection, (the absence of vomiting episodes,) was respectively 75%, 70% and 70% in the acute and 70%, 82%, 72% in the delayed phases, and an absence of nausea was 56%, 37% and 20% in the acute phase and 50%, 35% and 27% in the delayed, respectively. Complete response, (absence of vomiting and absence or mild nausea,) was 74%, 58.6% and 50.8% in the acute and 64%, 63.7%, 47.3% in the delayed phases, respectively. At the statistical analysis no significant differences between the three drugs were found regarding acute vomiting while ondansetron was superior to granisetron and tropisetron in acute (p = 0.018; p < 0.05) and delayed nausea (P = 0.104; p < 0.01). This activity is practically the same as that we reported (Ann Oncol 1994; 6, suppl 8: 204) with a loading dose on day 1 and maintenance for the following 2-5 days, but with a significantly favorable cost-benefit ratio.

Topics: Adolescent; Adult; Aged; Antiemetics; Antineoplastic Agents; Breast Neoplasms; Cisplatin; Cost-Benefit Analysis; Cyclophosphamide; Epirubicin; Female; Fluorouracil; Granisetron; Granulocyte Colony-Stimulating Factor; Humans; Indoles; Injections, Intravenous; Methotrexate; Middle Aged; Ondansetron; Serotonin Antagonists; Tropisetron; Vomiting

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.. 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.. 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.. Ondansetron, when given prophylactically resulted in a significantly lower incidence of PONV than metoclopramide and placebo. Metoclopramide was ineffective.

Topics: Adult; Aged; Antiemetics; Cholecystectomy, Laparoscopic; Double-Blind Method; Female; Granisetron; Humans; Indoles; Male; Metoclopramide; Middle Aged; Nausea; Ondansetron; Postoperative Complications; Prospective Studies; Serotonin Antagonists; Tropisetron; Vomiting

This study compares efficacy, safety and tolerability of 2 and 5 mg tropisetron in prevention of nausea and vomiting induced by low-dose cisplatin- or non-cisplatin-containing chemotherapy.. 152 chemotherapy-naïve cancer patients were randomized in a double-blind manner to receive 2 or 5 mg tropisetron intravenously day 1 and orally days 2-6. Primary efficacy criteria were control of acute (day 1) and delayed (days 2-6) vomiting and nausea. Secondary efficacy criteria included overall control (days 1-6) and control of vomiting and nausea by chemotherapy regimen. Safety and tolerability were evaluated clinically, biochemically and by the patient's diary. Only the first cycle was evaluated.. 124 of the 144 intention-to-treat patients were evaluable. There was a better total control (no events) of acute vomiting in the 5 mg (73%) than in the 2 mg group (55%, P = 0.02). Total control (< or = 15 minutes) of acute nausea was obtained in 70% of the 5 mg group and in 51% of the 2 mg (P = 0.03). No differences were observed for total control of delayed nausea or vomiting and for the overall outcome of nausea. Less vomiting (days 1-6) occurred in the 5 mg than in the 2 mg group. Efficacy rates ranged widely between chemotherapy regimens, independent of the tropisetron dose groups. There occurred more headache in the 5-mg group (P < 0.05).. Once daily 5 mg tropisetron is superior to 2 mg for prevention of acute vomiting and nausea induced by low-dose cisplatin- or non-cisplatin chemotherapy regimens, but causes more headache.

Topics: Administration, Oral; Adolescent; Adult; Aged; Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chi-Square Distribution; Cisplatin; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Indoles; Injections, Intravenous; Male; Middle Aged; Nausea; Neoplasms; Prospective Studies; Treatment Outcome; Tropisetron; Vomiting

The antiemetic effect of tropisetron was studied in 97 cancer patients (67 men, 30 women) receiving cisplatin in doses of 75 mg/m2 or higher. On 279 chemotherapy cycles studied (max 6 per patient) 5 mg of tropisetron was administered once a day i.v on day 1 and p.o. on days 2 to 6. Efficacy preventing vomiting and nausea was measured in 24 hour period as: complete control O episodes, major control 1 to 2 episodes, minor control 3 to 4 episodes and no control 5 or more episodes. Satisfactory vomiting control (complete and major) was 69%, 63%, 82%, 88%, 96% and 96% in days 1 to 6 of cycle 1. Satisfactory nausea control (complete and major) for the same days was 70%, 66%, 72%, 85%, 92% and 97%. Similar data was obtained for the subsequent cycles. Complete vomiting control was obtained in 47%, 35%, 56%, 72%, 81% and 84% and for nausea in 42%, 39%, 48%, 64%, 81% and 87%. 19 patients presented adverse effects (19.6%). Only 2 headache episodes had a definite relation with the antiemetic drug. 12 patients discontinued the medication; 6 due to drug inefficacy, 2 to illness unrelated to the drug, 1 to lack of collaboration, and 3 due to other reasons. We conclude that tropisetron allows satisfactory control of acute and delayed vomiting in a high percentage of patients treated with high doses of cisplatin. The drug does not have significant secondary effects. Tropisetron administration in only one daily dose implies an evident advantage and a treatment cost reduction.

Topics: Adolescent; Adult; Aged; Antiemetics; Antineoplastic Agents; Female; Humans; Indoles; Male; Middle Aged; Nausea; Neoplasms; Tropisetron; Vomiting

Thirty patients receiving cisplation or non-cisplatin (containing cyclophosphamide and adriamycin) chemotherapy were enrolled in a randomized, crossover study comparing the efficacy of single dose of Navoban (tropisetron, 5 mg) and Kytril (granisetron, 3 mg). The effective control of acute vomiting induced by cisplatin was achieved in 95.2% (20/21) of patients receiving Navoban and 90.5% (19/21) in those receiving Kytril. Complele control rate was 71.4% (15/21) in Navoban arm, and 81.0% (17/21) in Kytril arm. Total control of delayed vomiting (day 2-5) was 71.4%-90.4% in Navoban arm, while it was 66.7%-4% in Kytril arm. The effective control of vomiting induced by non-cisplatin drugs was achieved in 9/9 in both arms. It is concluded that both agents are effective in the control of vomiting induced by chemotherapy. They have identical adverse effects and are well tolerated by the patients.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Breast Neoplasms; Cisplatin; Female; Granisetron; Humans; Indoles; Lung Neoplasms; Lymphoma; Male; Middle Aged; Tropisetron; Vomiting

We have investigated the pharmacokinetics of a 5-day multiple oral dose of 5 mg tropisetron capsule in patients with malignant tumour who had received cisplatin single administration. Its anti-emetic effects on acute and delayed emesis and vomiting were also investigated. During the 5 days after this administration, changes in the release and metabolism of serotonin were investigated. The results may be summarized as follows: 1) The pharmacokinetic parameters of tropisetron revealed no significant change in the data between day 1 and day 5. Also, the parameters were almost similar to those observed in healthy adult males (clinical phase I study); Cmax. T1/2 and AUC 0-24 hrs on day 1 were 9.1 +/- 2.1 ng/ml, 12.5 +/- 4.2 hrs, 85.5 +/- 22.7 ng.hr/ml, respectively. The urinary excretion of the parent drug up until 24 hours after administration on day 1 was 3.8% of the dose administered and 2.9% of the total dose after the last administration; no difference in the urinary excretion rate was observed in healthy subjects. It was thus suggested that hydration accompanied by cisplatin administration did not affect the pharmacokinetics of tropisetron. 2) The changes in the amount of urinary excretion of 5-hydroxy-indoleacetic acid (5-HIAA) during 5 days after cisplatin administration were observed; urinary excretion of 5-HIAA increased 2.3 times (1.3-5.4 times) the baseline on the average during 6 to 12 hours on day 1. In 6 out of 10 patients, the increases in urinary excretion of 5-HIAA showed double or more the baseline during 2 to 5 days after cisplatin administration. Serotonin was thus deemed to be related to the development of delayed emesis. 3) The anti-emetic effects of tropisetron on acute and delayed emesis and vomiting were rated as "markedly effective" in 6 out of 11 patients (54.6%) and "effective" in 1 out of 11 patients (9.1%) on day 1; vomiting did not occur in any of these 7 patients. Tropisetron also controlled emesis and vomiting during days 2-5, and was rated as "almost favorable" in 6 out of 11 patients (54.5%). Further, in 4 out of 6 patients, in whom the urinary excretion of 5-HIAA was increased on day 2 onwards, vomiting did not occur during the time when the urinary excretion of 5-HIAA was increasing. On the basis of the above results, tropisetron is deemed to have certain antiemetic effects on delayed vomiting as well. Its 5-HT3 receptor mediated mechanism was similarly seen to inhibit acute nausea and vomiting.

Topics: Adult; Aged; Antiemetics; Capsules; Cisplatin; Drug Administration Schedule; Humans; Hydroxyindoleacetic Acid; Indoles; Lung Neoplasms; Male; Middle Aged; Nausea; Serotonin; Tropisetron; Vomiting

This study compared the efficacy and tolerability of tropisetron (Navoban, Novaban) alone or in combination with dexamethasone for the treatment of emesis induced by moderately emetogenic non-cisplatin chemotherapy. In total, 126 patients with cancer, who had never received chemotherapy and who required at least two courses of moderately emetogenic non-cisplatin chemotherapy each lasting for a minimum of 5 days, were recruited into the study. Patients were randomized to receive tropisetron, 5 mg o.d., plus either dexamethasone, 12 mg i.v. on day 1 followed by 4 mg orally b.i.d. on days 2-5, or placebo. Greater control of acute and delayed vomiting and nausea was achieved in patients given the tropisetron-dexamethasone combination than in those who received the tropisetron-placebo treatment. The majority of adverse events were mild and could be attributed to the chemotherapeutic regimen used or to the underlying disease. Patients and investigators both rated tropisetron alone or in combination with dexamethasone as a highly effective and well-tolerated antiemetic treatment. The results of this study show that tropisetron, 5 mg o.d., is an effective, well-tolerated and simple to use antiemetic treatment for patients receiving moderately emetogenic non-cisplatin chemotherapy. The addition of dexamethasone increases the efficacy of tropisetron without significantly decreasing its tolerability.

Topics: Antiemetics; Antineoplastic Agents; Dexamethasone; Double-Blind Method; Drug Combinations; Female; Humans; Indoles; Male; Middle Aged; Nausea; Neoplasms; Tropisetron; Vomiting

The antiemetic effect, safety and usefulness of once daily administration of tropisetron 5 mg capsule for 3 to 5 consecutive days was investigated in 37 cases of 12 stations in total, suffering from nausea and vomiting induced by a lower multiple dose of cisplatin. The efficacy ratings assessed every 24 hours on day 1, 2, 3, 4 and 5 were 88.6%, 85.7%, 82.9%, 74.1% and 76.9%, respectively. The final efficacy rating was 82.9% (29/35 cases). Although no adverse event was observed, increases in GOT and GPT, whose cause and relation to the investigational drug were unknown, were noted in 2 cases. Cases rated as useful or better were 82.9% (29/35 cases) of the overall. The above results reveal that tropisetron 5 mg capsule is significantly effective and highly safe in the treatment of nausea and vomiting induced by lower multiple dose of cisplatin. Tropisetron 5 mg capsule is thus deemed extremely useful antiemetic drug.

Topics: Antiemetics; Capsules; Cisplatin; Drug Administration Schedule; Female; Humans; Indoles; Male; Middle Aged; Nausea; Prostatic Neoplasms; Testicular Neoplasms; Tropisetron; Vomiting

A comparative clinical trial of tropisetron capsule was conducted in three dose groups to investigate its optimal dose on nausea and vomiting induced by anti-cancer drugs, including cisplatin. The doses were randomized by the central registration office. In the assessment of clinical efficacy, cases rated as "effective" or better accounted for 61.5% of the 2.5 mg group (16/26), 80.8% of the 5.0mg group (21/26) and 80.0% of the 10mg group (24/30), respectively; the ratings for the 5mg and 10mg groups were almost equivalent, which was higher than that for the 2.5mg group. Adverse events observed were fever, diarrhea, drowsiness, headache and/or facial erythema in 4 out of 97 cases. Abnormal laboratory findings noted were 6 cases of increased GOT, GPT, LDH, total bilirubin and/or creatinine, but none of these was serious or clinically problematic in particular. On the basis of the above results, the optimal dose of Tropisetron (capsule) is considered to be 5mg once daily.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Capsules; Cisplatin; Diarrhea; Drug Administration Schedule; Female; Fever; Head and Neck Neoplasms; Humans; Indoles; Lung Neoplasms; Male; Middle Aged; Nausea; Stomach Neoplasms; Tropisetron; Vomiting

A clinical phase III study of tropisetron capsule was conducted to assess its efficacy, safety and usefulness on nausea and vomiting induced by carboplatin or non-platinum anti-cancer drugs. The study was conducted in patients who experienced vomiting on previous chemotherapy. Tropisetron 5 mg capsule was given to patients once 2 hours prior to the first administration of either carboplatin or non-platinum anti-cancer drugs; the patients were then observed for nausea and/or vomiting during 24 hours after the first administration. Some 56.7% (17/30) of the patients did not vomit after tropisetron administration, and the frequency of vomiting was significantly reduced compared with that during the previous chemotherapy. Further, in the clinical efficacy ratings, in which the efficacy was assessed on the basis of the nausea and vomiting data, 83.3% (25/30) of cases were rated as "effective or better". Adverse events observed were 3 cases of mild headache, but these were not clinically problematic. The above results reveal that tropisetron capsule is significantly effective and safe in the treatment of nausea and vomiting induced by carboplatin or non-platinum anti-cancer drugs; in addition, tropisetron proved to be highly useful for its convenience as an oral agent.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Capsules; Carboplatin; Female; Humans; Indoles; Male; Middle Aged; Nausea; Neoplasms; Tropisetron; Vomiting

A placebo-controlled, double-blind comparative study of tropisetron capsule was conducted to assess its clinical usefulness for nausea and vomiting induced by the anticancer drug, cisplatin, at a single dose of 50 mg/m2 or higher. Either 5mg tropisetron capsule or its placebo was given orally to patients 2 hours prior to cisplatin administration; the clinical efficacy was determined the severity of nausea and the number of emesis that occurred during 24 hours after cisplatin. Tropisetron significantly exceeded the placebo in the assessment of clinical efficacy. The ratings for the tropisetron group and the placebo group were 91.7% (22/24 cases) and 25.9% (7/27 cases), respectively. Adverse events observed were one case of headache in the tropisetron group and one diarrhea in the placebo group, while neither case was serious nor clinically problematic in particular. The above results reveal that tropisetron 5 mg capsule is significantly effective in the treatment of anticancer drug-induced nausea and vomiting. It has also been confirmed that tropisetron is a useful agent without any safety problems.

Topics: Administration, Oral; Adult; Aged; Antiemetics; Capsules; Cisplatin; Double-Blind Method; Female; Head and Neck Neoplasms; Humans; Indoles; Lung Neoplasms; Male; Middle Aged; Nausea; Tropisetron; Vomiting

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Female; Humans; Indoles; Male; Middle Aged; Nausea; Neoplasms; Serotonin Antagonists; Treatment Outcome; Tropisetron; Vomiting

The purpose of this study was to evaluate and compare the antiemetic effectiveness and tolerability of Navoban (tropisetron) and Zofran (ondansetron) following high-dose (> or = 50 mg/m2) cisplatin chemotherapy. In a randomised, multi-centre, double-blind, double-dummy, parallel group study, 117 evaluable chemotherapy-naive patients who received Navoban were compared with 114 who received Zofran. Patient diary cards were used to assess both acute (Day 1) and delayed (Days 2-6) nausea and vomiting. Total control of acute vomiting was achieved in 54% of Navoban and 65% of Zofran patients (p = 0.052), and total control of acute nausea in 66% and 62% respectively (p = 0.655). Total control of delayed vomiting was achieved in 44% of Navoban patients and 46% of Zofran patients (p = 0.765), and of delayed nausea in 56% and 47% respectively (p = 0.207). Both reactions combined were totally prevented during the entire 6-day trial period in 22% of Navoban and 24% of Zofran patients (NS), while a further 42% of patients in both groups remained largely free from both nausea and emesis. The few adverse reactions (e.g. headache, constipation, diarrhoea) were mainly mild and typical of the 5-HT3-receptor antagonists. In conclusion, there were no significant differences in efficacy and tolerability between Navoban 5 mg once daily and the highest recommended dose of Zofran (32 mg on Day 1, followed by 8 mg three times a day).

Topics: Antiemetics; Cisplatin; Double-Blind Method; Female; Humans; Indoles; Male; Middle Aged; Nausea; Neoplasms; Ondansetron; Tropisetron; Vomiting

Even with the availability of potent and selective serotonin antagonists, chemotherapy-induced nausea and vomiting remain a major problem for many patients. This study aims to evaluate the benefit of combination therapy based on Navoban (tropisetron) in patients who had incomplete control of nausea and/or vomiting induced by chemotherapy when using Navoban as a single antiemetic agent. In their first chemotherapy course, 1072 patients planned to receive at least two identical cycles of emetogenic chemotherapy were treated with 5 mg Navoban once daily. To evaluate three treatments additional to the recommended 5 mg once-daily Navoban regimen during Course 2 in those patients who had shown incomplete control of nausea and/or vomiting on any day of Course 1, a 2 x 2 x 2 factorial design was employed. Of these patients, 445 were centrally randomised to receive an additional dose of open-label dexamethasone (Day 1, 0.2 mg/kg i.v.; Days 2-6, 8 mg p.o.) and/or open-label alizapride (Day 1, 100 mg i.v. and 4 x 50 mg p.o.; Days 2-6, 4 x 5 mg p.o.) and/or double-blind Navoban--that is, doubling the dose to 10 mg once daily or placebo. Complete response rates during Course 1 (CRR, no nausea and no vomiting) were, for Day 1, 72% and for Days 1-6, 48%. More complete responders were observed when dexamethasone was added during Course 2, both on Day 1 (76% vs. 66%, p = 0.020) and on Days 1-6 (50% vs. 34%, p = 0.0004).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Indoles; Male; Middle Aged; Nausea; Neoplasms; Patient Compliance; Prognosis; Pyrrolidines; Tropisetron; Vomiting

To evaluate the efficacy and safety of Navoban (tropisetron) three different Nordic multicentre trials were conducted during the period 1988-92. In all, 1050 patients were recruited from 15 centres. In the first study, Navoban monotherapy was compared with a high-dose metoclopramide cocktail. In the second, Navoban +/- dexamethasone was evaluated for those patients not fully protected by Navoban alone. In the third trial, Navoban was evaluated for various chemotherapy regimens, for long-term efficacy, and for various risk groups of patients. Spontaneous intercycle variations were also evaluated. Navoban was found to be as effective as the antiemetic cocktail but with a more favourable spectrum of side effects and a simpler schedule of administration. Navoban was more effective during the acute than the delayed phase. Addition of dexamethasone significantly improved prevention of both acute and delayed emesis. Long term efficacy seemed to be stable up to 10 cycles of chemotherapy. Patients treated with noncisplatin regimens showed significantly higher protection rates than patients treated with cisplatin. Various cancer diagnoses and cytostatic agents were also evaluated. Gender and age were important risk factors. Navoban was found to be an efficacious antiemetic agent, especially regarding acute nausea and vomiting. Addition of a corticosteroid significantly improved the effect during highly emetogenic chemotherapy. The role of Navoban for delayed emesis must be evaluated in future trials. The two most common side effects were headache and constipation. Overall, Navoban was well tolerated and patient compliance with the drug was high.

Topics: Antiemetics; Antineoplastic Agents; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Indoles; Male; Nausea; Neoplasms; Risk Factors; Sweden; Tropisetron; Vomiting

One hundred and thirty-one children with a median age of 5 years were administered Navoban (tropisetron), a selective antagonist of the serotonin receptor (5-HT3), dosed once daily at 0.2 mg/kg (with a maximum of 5 mg daily) in a study aimed at evaluating the prevention of nausea and vomiting induced by anti-cancer chemotherapy. The most common malignancy (in 49% of patients) was acute lymphocytic leukaemia. Patients received Navoban during one or more courses of emetogenic chemotherapy for a total of 455 courses administered intravenously or intravenously and intrathecally (IV + IT). Most patients (89%) had already received cytotoxic chemotherapy before enrollment for the trial. On Day 1, Navoban was administered slowly and intravenously as a single dose before the start of chemotherapy, or by mouth as a single daily dose on subsequent days (median treatment duration = 5 days). On the first 5 days of each course of chemotherapy, response to Navoban per 24-hour period was graded as: complete (absence of both nausea and vomiting), partial (1-4 vomits and/or less than 5 hours of nausea), or failure (more than 4 vomits and/or at least 5 hours of nausea). Ninety-six per cent of the intravenous chemotherapy group and 97% of the IV + IT chemotherapy group had a complete (70% and 55% respectively) or partial (26% and 42% respectively) response during the first 24-hour period of the first course in which Navoban was used. The second and subsequent courses yielded similar percentages. Delayed emesis was observed mainly during those courses employing the most emetogenic chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Antiemetics; Antineoplastic Agents; Child; Child, Preschool; Female; Humans; Indoles; Infant; Male; Nausea; Neoplasms; Prospective Studies; Tropisetron; Vomiting

We investigated the potential of cross-over to the serotonin receptor (5HT3) antagonist ondansetron after protection failure with tropisetron. Several cases of complete protection were observed. These limited data suggest that there is an indication for retreatment with a different 5HT3 antagonist after an initial failure to another and also stress the need and relevance for comparative studies between 5HT3 antagonists.

Topics: Adult; Aged; Antiemetics; Cisplatin; Cross-Over Studies; Drug Resistance; Female; Humans; Indoles; Male; Middle Aged; Nausea; Ondansetron; Pilot Projects; Serotonin Antagonists; Tropisetron; Vomiting

The antiemetogenic effect of navoban (Sandoz) was studied in 26 patients receiving chemotherapy, with application of platidiam in 22 cases included. No vomiting was registered. Nausea was observed in 9 cases within the first 24 hrs and a slight reduction in appetite--in 13 cases. Navoban proved one of the most potent antiemetics devoid of any untoward side-effects.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Female; Humans; Indoles; Male; Middle Aged; Nausea; Treatment Outcome; Tropisetron; Vomiting

In a double-blind, placebo-controlled, escalating dose study, 44 children receiving cancer chemotherapy of various degrees of emetogenicity were randomly allocated to once-daily treatment with tropisetron 0.05 mg/kg (6 patients), 0.10 mg/kg (5 patients), 0.20 mg/kg (6 patients), 0.33 mg/kg (6 patients), 0.50 mg/kg (6 patients) or placebo (15 patients). All doses of tropisetron were well tolerated; no tropisetron recipient discontinued treatment because of intolerance and no adverse effect could be plausibly correlated to tropisetron administration. Therapeutic plasma concentrations of tropisetron (> 3 ng/ml) were present for 9 h after administration of doses of 0.10 mg/kg or more. Tropisetron at doses of at least 0.20 mg/kg was significantly more effective in preventing vomiting than lower tropisetron doses or placebo, both in terms of treatment failure (> four vomits) (P = 0.015) and patient and investigator efficacy ratings (P = 0.04 for investigator rating; P = 0.035 for patient rating). Further comparative studies of the efficacy of tropisetron in chemotherapy-induced emesis in children are warranted.

Topics: Adolescent; Antiemetics; Antineoplastic Agents; Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Indoles; Male; Nausea; Serotonin Antagonists; Tropisetron; Vomiting

The purpose of these two studies was to define the optimal therapeutic dose of the 5-HT3 receptor antagonist tropisetron (Navoban, ICS 205-930) in cisplatin-induced nausea and vomiting.. In two multicentre, dose-finding studies of tropisetron in the prevention of cisplatin-induced emesis, cancer patients naïve to chemotherapy or who had not vomited previously were randomly assigned to tropisetron 5, 10, 20 or 40 mg (study I, 143 patients) or 2 or 5 mg (study II, 74 patients), administered as a single intravenous dose over 15 minutes just before the start of chemotherapy.. In study I total control of acute symptoms (no nausea and no vomiting) was achieved in, respectively, 66%, 50%, 64% and 50% in the 5-, 10-, 20- and 40-mg groups of patients. A total absence of vomiting alone was seen in, respectively, 71%, 51%, 61% or 58% of patients. None of the differences were statistically significant. In study II there was total acute control in 57% of patients in the 2-mg group and 63% in the 5-mg group (p = NS). Total or major control of vomiting (< or = 2 emetic episodes) was the primary endpoint in study II and was seen in 68% of patients for the 2-mg and 86% for the 5-mg group (p = 0.055). In this study failures ( > 3 vomiting) were rescued with a second infusion of tropisetron (5-mg fixed dose). Three of 8 rescue infusions administered in the 2-mg group prevented further vomiting whereas none of 5 were successful in the 5-mg group during course 1 of chemotherapy. The most frequently reported adverse effects (over all three courses) were headache (6.0% of 217 patients) hypertension (3.7%) and diarrhoea (2.8%). None of the 25 deaths which occurred during the two studies were attributable to tropisetron.. Thus, a single dose of tropisetron provides 24-hour protection against cisplatin-induced nausea and vomiting and is well tolerated. These studies do not allow a firm conclusion but suggest that 2 mg may be subtherapeutic and that 5 mg is as effective as higher doses.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Cisplatin; Drug Administration Schedule; Female; Humans; Indoles; Male; Middle Aged; Nausea; Neoplasms; Tropisetron; Vomiting

An open, noncomparative, Nordic multicenter study was carried out during 1991-1992 to evaluate the 5-HT3 receptor antagonist tropisetron (Navoban) as an antiemetic agent for various types of cancer chemotherapy. A total of 630 patients were recruited from 15 centers in Sweden, Denmark, and Finland. Gynecological cancers (60%), breast cancer (15%), and lung cancer (10%) were the main diagnoses. Prior experience of chemotherapy was documented in 338 patients (54%). In 260 patients (41%), cisplatin was part of the cytostatic regimen. Carboplatin (23%), doxorubicin (27%), and epidoxorubicin (24%) were also frequently included. In all, 23 cytostatic agents were used in various combinations. The mean number of courses studied was 4.6 (range 1-19). Altogether, 394 of 619 evaluable patients (64%) were completely protected from acute nausea and vomiting during the first course of chemotherapy. Delayed nausea and vomiting were completely prevented in 45%-73% (days 2-6) in the complete series. Treatment efficacy remained stable (60%-79%) during ten consecutive courses of chemotherapy. With noncisplatin regimens, complete protection from acute nausea and vomiting was achieved in 72% compared with 52% for cisplatin regimens (P < 0.0001). Patients without prior experience of chemotherapy had higher control rates of acute nausea and vomiting (72%) compared to patients treated before (57%) during the first course, but not later on. There were no differences in delayed nausea and vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Female; Finland; Humans; Indoles; Male; Middle Aged; Nausea; Neoplasms; Scandinavian and Nordic Countries; Sex Factors; Treatment Outcome; Tropisetron; Vomiting

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Humans; Indoles; Nausea; Pyrrolidines; Tropisetron; Vomiting

High doses of metoclopramide are contraindicated to prevent chemotherapy-induced emesis in pediatric patients, since the incidence of extrapyramidal reactions is increased in these patients. The aim of this small study was to evaluate the antiemetic activity and the safety of tropisetron (a new selective antagonist of 5-HT3 receptors) in children who suffered nausea and vomiting during previous chemotherapy courses, despite the administration of an anxiolytic agent (hydroxyzine hydrochloride).. The children with a malignant neoplasm were treated for emesis with tropisetron (5 mg o.a.d. or b.i.d.) during a total of 20 cycles of chemotherapy with carboplatin combined with other antitumor agents.. In 14 cycles (70%), there was no vomiting. There were two or less episodes of vomiting in 2 cycles (10%), 3-4 episodes in 2 cycles (10%), and no inhibition of vomiting at all in 2 cycles (10%). In 8 cycles there were no episodes of nausea (40%), in 5 cycles (25%) there were episodes of moderate nausea, and in 4 (20%) there were episodes of severe nausea. One child had a mild headache during one cycle and moderate hypotension during another.. The results suggest that tropisetron is both efficacious and safe for the treatment of pediatric patients.

Topics: Adolescent; Antiemetics; Antineoplastic Agents; Child; Child, Preschool; Drug Administration Schedule; Female; Humans; Indoles; Infant; Male; Nausea; Neoplasms; Serotonin Antagonists; Treatment Outcome; Tropisetron; Vomiting

Fourteen cancer patients treated with cisplatin received repeated infusions of tropisetron on-demand in conjunction with emesis. In subsequent chemotherapy courses, prophylactic tropisetron was given in a dose identical to the cumulated dose in study course 1. Tropisetron in study course 1 abolished emesis after 7.5 min (5 mg). Duration of effect was more than 7 h in 50% of the patients. No relationship between dose and duration of effect was seen. After study course 2, eight of 10 patients preferred prophylactic tropisetron. Two patients with hypertension had a severe increase in blood pressure probably related to tropisetron. It is concluded that tropisetron has an instant and lasting effect on nausea and vomiting when given on-demand. The majority of patients, however, prefer prophylactic treatment. Hypertension may be a side effect from tropisetron and caution should be displayed in hypertensive patients.

Topics: Adult; Aged; Antiemetics; Cisplatin; Dose-Response Relationship, Drug; Female; Head and Neck Neoplasms; Humans; Indoles; Male; Middle Aged; Nausea; Ovarian Neoplasms; Serotonin Antagonists; Tropisetron; Vomiting

This study evaluated tropisetron (Navoban; Sandoz Pharma, Basle, Switzerland)-based combination therapy in patients who had incomplete control of chemotherapy-induced nausea or vomiting when using tropisetron as a single antiemetic agent.. One thousand seventy-two patients, who were scheduled to receive at least two identical cycles of emetogenic chemotherapy, were treated with 5 mg tropisetron once daily in their first chemotherapy course. A 2 x 2 x 2 factorial design was used to evaluate three additional treatments to the recommended 5 mg once daily (intravenously [i.v.] on day 1; orally on days 2 through 6) tropisetron regimen during course 2 in those patients who had shown incomplete control of nausea and/or vomiting on any day of course 1. Four hundred forty-five patients were centrally randomized to receive, in addition, open-label dexamethasone (day 1, 0.2 mg/kg i.v.; days 2 through 6, 8 mg orally) and/or open-label alizapride (day 1, 100 mg i.v. and 4 x 50 mg orally; days 2 through 6, 4 x 50 mg orally) and/or double-blind tropisetron (ie, doubling the dose to 10 mg once daily) or corresponding placebo.. Complete response rates (no nausea and no vomiting) were 72% for day 1 and 48% for days 1 through 6 of course 1. During course 2, more complete responders were observed when dexamethasone was added, both for day 1 (76% v 66%, P = .020) and for days 1 through 6 (50% v 34%, P = .0004). A moderate increase in the complete response rate was seen with the addition of conventional-dose alizapride (day 1, 75% v 68%, P = .14; days 1 through 6: 47% v 37%, P = .041). Doubling the dose of tropisetron did not change the complete response rate.. The addition of dexamethasone significantly increases the complete response rate of both acute and delayed emesis in patients who have incomplete disease control with tropisetron alone.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Dose-Response Relationship, Drug; Double-Blind Method; Drug Interactions; Female; Humans; Indoles; Injections, Intravenous; Male; Middle Aged; Nausea; Prognosis; Prospective Studies; Pyrrolidines; Tropisetron; 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.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Female; Humans; Indoles; Male; Metoclopramide; Middle Aged; Nausea; Tropisetron; Vomiting

In a double-blind, randomised, multicentre study, the efficacy and tolerability of tropisetron and a combination of tropisetron and dexamethasone were compared for the control of nausea and vomiting induced by cisplatin in patients previously not entirely protected by tropisetron monotherapy. In all, 160 women with gynaecological cancers were studied during two consecutive courses of cisplatin-containing chemotherapy. During the first course (the screening course), all patients received tropisetron monotherapy [5 mg intravenous (i.v.) on day 1 and 5 mg orally on days 2-6] as antiemetic treatment. During the second course (the test course), tropisetron was compared with a combination of tropisetron and dexamethasone (20 mg i.v. on day 1 and 4.5 mg twice daily on days 2-6). This part of the study was double-blind, randomised and placebo-controlled. Candidates for randomisation were patients with partial control of nausea (< 12 h of nausea) or partial control of vomiting (1-4 episodes of vomiting) during the screening course. Patients with complete control of nausea and vomiting in the screening course continued with tropisetron monotherapy; patients with treatment failure received open rescue treatment in course 2. Total control of acute nausea was achieved in 37% of the tropisetron + placebo group and in 75% of the tropisetron + dexamethasone group (P = 0.001). Significantly more patients on tropisetron-dexamethasone than on tropisetron-placebo were also free of delayed nausea. Acute vomiting was prevented in 40% of the patients in the placebo group and in 75% in the dexamethasone group (P = 0.001). Delayed vomiting was also significantly less frequent in dexamethasone-treated patients than in placebo-treated patients. Tropisetron was well tolerated both as monotherapy and in combination with dexamethasone. The most frequent adverse events were headache (34%), constipation (12.5%) and fatigue (12.5%). Adding high doses of a corticosteroid did not induce further adverse events or disregulate concurrent diseases.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Cisplatin; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Female; Genital Neoplasms, Female; Humans; Indoles; Middle Aged; Nausea; Tropisetron; Vomiting

Nausea and vomiting are among the most distressing side-effects of chemoradiotherapy. Conditioning protocols for patients undergoing bone marrow transplantation consist of highly emetogenic high-dose chemotherapy with or without total body irradiation. Marked improvement in controlling emesis and nausea was achieved by the introduction of a new class of antiemetic drugs, the 5HT3 serotonin-receptor antagonists. Tropisetron is a highly potent, selective antagonist of 5HT3 receptors. Previous studies have used a single 5-mg dose i.v. of tropisetron to control nausea and vomiting in cancer patients. The present study was undertaken to evaluate the efficacy and safety of a single daily dose of tropisetron in controlling emesis in patients receiving high-dose chemotherapy (with or without total body irradiation) prior to bone marrow transplantation. The anti-emetic efficacy was investigated in a non-homogeneous cohort in a prospective and open study. Of 11 patients evaluated, 9 (81%) showed complete or major control, 1 (9%) minor control and 1 (9%) failed to respond. The most common adverse events reported during the study included diarrhea (46%) and headache (18%), no patients being withdrawn because of side-effects. Our data suggest that a single 5-mg i.v. dose of tropisetron is safe and effective in preventing chemotherapy-induced emesis in patients receiving bone marrow transplantation conditioning. A larger randomized study is warranted to confirm our preliminary results.

Topics: Adolescent; Adult; Antiemetics; Antineoplastic Agents; Bone Marrow Transplantation; Child; Child, Preschool; Cohort Studies; Combined Modality Therapy; Diarrhea; Drug Tolerance; Female; Headache; Humans; Indoles; Male; Middle Aged; Nausea; Prospective Studies; Safety; Serotonin Antagonists; Tropisetron; Vomiting; Whole-Body Irradiation

This placebo-controlled, randomized, double-blind trial was designed to evaluate the efficacy of three prophylactic antiemetic regimens on postoperative nausea and vomiting (PONV) during patient-controlled analgesia (PCA) with morphine. We studied 286 elective surgical patients for 36 h postoperatively. Group 1 was saline control. In Groups 2 and 3, metoclopramide or droperidol was administered as an intravenous (i.v.) bolus and then added to morphine in the PCA device. In Group 4, tropisetron, a long-acting investigational 5-hydroxytryptamine subtype 3 (5-HT3) antagonist was given as a single i.v. dose. We assessed the frequency and severity of PONV, as well as the need for rescue, frequency of side effects, and overall patient satisfaction. Severity of PONV was measured with a symptom-severity score (STS) which was based on both intensity and duration. The average total doses of antiemetics were metoclopramide 53.8 +/- 2.2 mg, droperidol 5.99 +/- 0.3 mg, and tropisetron 6.1 +/- 0.2 mg. Control patients had a 54% incidence of PONV. Droperidol reduced both the incidence (P < 0.001) and severity (P < 0.01) of PONV for the entire 36 h. Tropisetron reduced incidence and severity (P < 0.05), but the effect of the single bolus dose lasted only 18 h. Metoclopramide had a marginally significant effect under these conditions. Only droperidol decreased the need for rescue medication (P < 0.01), although rescue with tropisetron was highly effective. Side effects and patient satisfaction were comparable among the groups, but patients receiving droperidol were sleepier (P < 0.05) than control patients and recalled somewhat more anxiety (P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Analgesia, Patient-Controlled; Antiemetics; Double-Blind Method; Droperidol; Elective Surgical Procedures; Female; Humans; Indoles; Male; Metoclopramide; Middle Aged; Morphine; Nausea; Postoperative Complications; Tropisetron; Vomiting

In a prospective randomized study comprising 66 women treated for gynecologic malignancies with cisplatin-containing chemotherapy, the new 5-hydroxytryptamine3 (5-HT3) receptor antagonist tropisetron (Navoban, Sandoz Pharma Ltd.) was compared with a metoclopramide cocktail for the prevention of nausea and emesis. All patients were chemotherapy-naive. Two consecutive courses (including the 1st week posttherapy) were studied. The cisplatin doses were in the range of 50-75 mg/m2, and the regimens also contained doxorubicin, teniposide, etoposide, vincristine, and bleomycin. Complete protection against nausea during the first 24 h (course 1) was achieved in 76% of the tropisetron group and in 85% of the metoclopramide group. Emesis was prevented in 82% of the patients in both groups. During the whole 6-day period, full emetic protection was achieved in 30% and 18% of the patients in the two groups. On days 3-4 of course 1, tropisetron was superior to metoclopramide. The overall tolerability of the tropisetron was excellent or good in 94% of patients, a rate higher than that observed for the metoclopramide regimen (75%). The most common side effects for the latter regimen were sedation (82%) and extrapyramidal reactions (21%). The only significant adverse event recorded after treatment with tropisetron was headache of slight or moderate grade.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Cisplatin; Drug Administration Schedule; Female; Genital Neoplasms, Female; Humans; Indoles; Metoclopramide; Middle Aged; Nausea; Prospective Studies; Serotonin Antagonists; Treatment Outcome; Tropisetron; Vomiting

Chemotherapy-induced emesis is one of the most disturbing side effects in cancer therapy. Thus, antiemetic treatment is a mandatory adjunct in emetogenic chemotherapy.. Tropisetron (Navoban, Sandoz Pharma Ltd., Basel, Switzerland), a new 5-HT3 receptor antagonist, was compared in a randomized multicenter trial with a high-dose metoclopramide-dexamethasone cocktail for the prevention of nausea and emesis during cisplatin-containing chemotherapy. Two hundred fifty-nine chemotherapy-naive patients were included and followed during two consecutive courses. The main cancer types were gynecologic tumors, followed by lung cancer, head and neck cancer, and bladder cancer. The cisplatin dose usually was in the range of 50-89 mg/m2. The efficacy and quality of life assessments and the safety recordings were done during the first 6 days of both courses of chemotherapy.. Acute vomiting was prevented in 63-64% of patients by both antiemetic regimens. The total rate of control of vomiting increased from 63% on day 1 to 93% on day 6 in the group receiving tropisetron. Acute nausea was prevented in 40% of the patients with tropisetron monotherapy and in 61% of patients receiving the antiemetic cocktail. With regard to delayed nausea, there were no significant differences between the two antiemetic regimens. Mild headache and constipation were more frequently associated with tropisetron, and extra-pyramidal side effects and sedation were associated with the antiemetic cocktail.. Tropisetron was easier to administer and better tolerated than the cocktail, and it seems to be a highly efficacious and safe new antiemetic drug.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Cisplatin; Female; Humans; Indoles; Male; Metoclopramide; Middle Aged; Nausea; Neoplasms; Quality of Life; Tropisetron; Vomiting

This report of a double-blind, randomized study performed to evaluate the comparative antiemetic efficacy of tropisetron (Navoban; Sandoz Pharma Ltd, Basel, Switzerland), a new 5-hydroxytryptamine receptor antagonist, focuses on treatment during stages of chemotherapy when nausea and vomiting are particularly severe. One hundred fifteen chemotherapy-naive patients with malignant disease were administered either tropisetron (n = 58) or a dexamethasone dose plus a metoclopramide dose (n = 57) during 5 days of two successive cycles of chemotherapy. Within the first 24 hours after receiving cisplatin-based chemotherapy, 76% of patients in the tropisetron group remained free of vomiting (with 59% of patients free of nausea) compared with 39% of patients free of vomiting in the conventionally treated group (30% of patients free of nausea). Improved control of emesis also was observed over 4 consecutive days of follow-up in the tropisetron group. The difference in incidence of nausea and vomiting between the patient groups was statistically significant (P < .05). The efficacy of tropisetron was well maintained during the second consecutive chemotherapy cycle; during the first 24 hours, 72% and 62% of patients remained free of vomiting and nausea, respectively. Tropisetron appears to be a highly effective, well tolerated, and simple to use antiemetic agent for patients receiving chemotherapy.

Topics: Adult; Antiemetics; Antineoplastic Agents; Cisplatin; Dexamethasone; Dopamine Antagonists; Double-Blind Method; Female; Humans; Indoles; Male; Metoclopramide; Middle Aged; Nausea; Neoplasms; Serotonin Antagonists; Treatment Outcome; Tropisetron; Vomiting

In this double-blind, randomized trial performed at five study centers, the prophylactic, antiemetic effect of two different dosages of tropisetron (Navoban; Sandoz Pharma Ltd, Basel, Switzerland) was investigated in dacarbazine-treated patients with melanoma. Patients received tropisetron 5 mg or 10 mg orally (as one capsule) once daily (minimum 3 days) on each day of chemotherapy. No significant differences were found in the effects of tropisetron 5 mg and 10 mg. During the first 24 hours, total control of vomiting was seen in 93% and 98% of patients receiving tropisetron 5 mg and 10 mg, respectively. Total control of nausea was achieved in 84% and 80% of patients receiving tropisetron at these dosages. Over days 2 to 7 of chemotherapy, total control of vomiting and nausea remained high. Patients reported that quality of life remained good throughout chemotherapy, as did mood; only a small decrease in food intake occurred. Tropisetron was well tolerated. Constipation was the most common adverse event, occurring in 13% of patients. Headache (4%), diarrhea (4%), and anorexia (2%) also were observed.

Topics: Administration, Oral; Adult; Aged; Antiemetics; Antineoplastic Agents; Dacarbazine; Double-Blind Method; Drug Administration Schedule; Female; Humans; Indoles; Male; Melanoma; Middle Aged; Nausea; Quality of Life; Serotonin Antagonists; Tropisetron; Vomiting

We report an open, three-armed, multicenter study being carried out to assess the optimum treatment for acute and delayed emesis and nausea in patients undergoing highly emetogenic chemotherapy. Eighty-seven patients were randomized to receive tropisetron (Navoban; Sandoz Pharma Ltd, Basel, Switzerland), tropisetron plus dexamethasone, or tropisetron plus metoclopramide during chemotherapy. Tropisetron in combination with dexamethasone produced the best control of both acute and delayed emesis. Acute vomiting was prevented in 69% of patients by tropisetron monotherapy, and the addition of dexamethasone significantly increased the total control of vomiting to 92% (P < .01). Similarly for delayed vomiting, total control of emesis was seen in approximately 70% of patients on tropisetron alone during days 2 and 3; this control rate increased to almost 90% with combined tropisetron/ dexamethasone treatment. In all patients receiving cisplatin, the tropisetron/dexamethasone combination produced total control of acute emesis. The tropisetron and dexamethasone combination also provided the best control of acute and delayed nausea. Tropisetron produced total control of acute nausea in 69% of patients. The addition of dexamethasone increased this control rate to 81%. Similarly for delayed nausea, on days 2 and 3 of treatment, dexamethasone plus tropisetron provided total control of nausea in more than 80% of patients compared with a control rate of more than 60% achieved using tropisetron. The combination of tropisetron and metoclopramide did not improve significantly on the control of nausea and vomiting achieved using tropisetron alone. Evaluation of quality of life events by patients indicated no appreciable change in their mental or physical condition during chemotherapy, irrespective of antiemetic therapy. In the tropisetron and tropisetron plus metoclopramide treatment groups, a decreased food intake was observed due to delayed nausea while the addition of dexamethasone prevented loss of appetite. The antiemetic treatments were similarly well tolerated. The most common adverse events were constipation (15%) and tiredness (7%).

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Dexamethasone; Dopamine Antagonists; Drug Therapy, Combination; Female; Humans; Indoles; Male; Metoclopramide; Middle Aged; Nausea; Neoplasms; Serotonin Antagonists; Treatment Outcome; Tropisetron; Vomiting

Emesis is one of the most frequent and distressing adverse effects of cytotoxic chemotherapy. Conventional antiemetic regimens are unsatisfactory due to their poor efficacy and their adverse events, particularly in children. Tropisetron (Navoban; Sandoz Pharma Ltd, Basel, Switzerland) belongs to a new class of 5-hydroxytryptamine receptor antagonists with antiemetic effectiveness in patients receiving anticancer agents. We evaluated tropisetron (0.2 mg/kg/d) in 24 chemotherapy-treated children who had experienced severe emesis during previous chemotherapy courses in spite of concomitant administration of either alizapride or metoclopramide. Complete control of emesis was achieved in 70% of the courses (37% of those including cisplatin). No severe adverse effect was reported. Headache was observed in two courses and constipation was observed during two other courses. Tropisetron proved clearly superior to conventional antiemetics and safe in use.

Topics: Adolescent; Antiemetics; Antineoplastic Agents; Child; Child, Preschool; Dopamine Antagonists; Female; Humans; Indoles; Infant; Male; Metoclopramide; Nausea; Neoplasms; Pyrrolidines; Serotonin Antagonists; Tropisetron; Vomiting

Three Nordic multicenter studies were performed between 1988 and 1992 to evaluate the efficacy of tropisetron (Navoban; Sandoz Pharma Ltd, Basel, Switzerland) as an antiemetic agent in patients undergoing various types of chemotherapy. More than 1,050 patients were recruited from cancer centers in Sweden, Finland, and Denmark. In the first two studies, chemotherapy-naive patients were studied for 6-day periods over two consecutive treatment cycles. The first study comparing tropisetron with a metoclopramide cocktail was performed as an open, randomized, multicenter, parallel-group study. All 259 chemotherapy-naive patients received cisplatin > or = 50 mg/m2 on the first day of chemotherapy; other cytostatic agents were allowed on days 1 to 6 of therapy. Patients received either tropisetron or an antiemetic cocktail of metoclopramide, dexamethasone, and lorazepam over the study period. Total control of acute vomiting during the first course of chemotherapy was achieved in 63% of patients in the tropisetron treatment group and in 64% of patients in the antiemetic cocktail group. Acute nausea was prevented completely in 40% of patients in the tropisetron group and in 61% of the metoclopramide cocktail group during course 1 (P < .001). For delayed nausea and vomiting, there were no significant differences between the two antiemetic regimens. Both antiemetic regimens were well tolerated. The second study compared the efficacy of tropisetron plus placebo with tropisetron plus dexamethasone for the prevention of acute and delayed nausea and vomiting during cisplatin-containing chemotherapy in patients not fully controlled by tropisetron monotherapy during course 1. One hundred sixty patients were involved in this double-blind, randomized, placebo-controlled trial. Acute vomiting was completely prevented in 40% of patients treated with tropisetron plus placebo compared with 75% of patients treated with tropisetron plus dexamethasone (P = .001). The results for acute nausea were similar. Delayed vomiting and delayed nausea were completely prevented in significantly more patients receiving the tropisetron-dexamethasone combination than in those receiving the tropisetron-placebo combination (P < .05). Adverse events were reported less frequently in patients receiving tropisetron together with dexamethasone. The third study was an open, nonrandomized multicenter trial designed to investigate the long-term antiemetic effect of tropisetron on various types of chemother

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Dexamethasone; Dopamine Antagonists; Drug Therapy, Combination; Female; Humans; Indoles; Male; Metoclopramide; Middle Aged; Nausea; Neoplasms; Serotonin Antagonists; Tropisetron; Vomiting

In a double-blind study, we have compared the prophylactic antiemetic effect of tropisetron 5 mg (Navoban, a 5-HT3 receptor antagonist) with that of placebo, both given as a short i.v. infusion approximately 15 min before wound closure in patients undergoing gynaecological surgery. Perioperative anaesthetic care was standardized and patients were observed for at least 24 h after operation. The 35 patients given tropisetron and 34 given placebo treatment were well matched for characteristics. Vomiting occurred in 26% of tropisetron-treated patients, compared with 59% of placebo-treated patients (P = 0.006); 69% of tropisetron-treated patients suffered nausea, compared with 88% of placebo-treated patients (P = 0.05). In addition, patients judged the antiemetic treatment with tropisetron as more effective than the placebo treatment (visual analogue score 71 vs 51 mm (P = 0.003)).

Topics: Adult; Aged; Double-Blind Method; Female; Genital Diseases, Female; Humans; Indoles; Middle Aged; Nausea; Postoperative Complications; Serotonin Antagonists; Tropisetron; Vomiting

We have studied the effect of tropisetron, a 5-HT3-receptor antagonist, on postoperative nausea, vomiting and pain in 54 patients, aged 50-83 yr, after major hip or knee surgery. The patients were given subarachnoid injection of plain 0.5% bupivacaine, mixed with preservative-free morphine 0.3 mg, for surgical and postoperative analgesia. In a double-blind fashion, either tropisetron 5 mg (1 mg ml-1) or saline 5 ml was injected i.v. 30 min after spinal administration of bupivacaine and morphine. The number of patients needing i.m. oxycodone for pain relief, the total number of oxycodone doses or the mean time to the first i.m. oxycodone administration did not differ significantly between the two groups. The number of patients who became nauseated or vomited during the observation period did not differ significantly between groups. Seventeen patients had nausea and 11 vomited in the tropisetron group, compared with 20 and 13, respectively, in the control group during the first 24 h.

Topics: Aged; Aged, 80 and over; Anesthesia, Spinal; Bupivacaine; Double-Blind Method; Female; Humans; Indoles; Injections, Spinal; Male; Middle Aged; Morphine; Nausea; Oxycodone; Pain Measurement; Pain, Postoperative; Postoperative Complications; Serotonin Antagonists; Tropisetron; Vomiting

An open, two-armed, multicentre trial was conducted in 231 patients with malignant disease who had previously failed to respond to conventional antiemetic treatment for the prevention of chemotherapy-induced nausea and vomiting. Patients were randomized to receive either tropisetron (5 mg/day; n = 115) or a standard antiemetic therapy, which was considered optimal for each individual but did not include a 5-HT3 receptor antagonist (n = 116). Acute vomiting on Day 1 was controlled in 60 (52%) tropisetron patients, compared with only 29 (25%) patients receiving optimal standard therapy (p < 0.001). Acute nausea was completely inhibited in 37 (32%) tropisetron patients, compared with 22 (19%) patients on optimal standard therapy (p < 0.05). On Day 1, delayed vomiting was also significantly better prevented by tropisetron (p < 0.001). Side effects from tropisetron (headache and constipation) were mild, and no extrapyramidal symptoms were observed in any tropisetron patients, in contrast, to 14 (13%) patients in the 'optimal standard' group. In conclusion, in cases of acute nausea and vomiting it is more effective to switch refractory patients to tropisetron rather than attempt to optimize the dose of standard antiemetic therapy. For delayed nausea and vomiting, combination antiemetic therapy, with differing types of receptor antagonism and corticosteroids may provide the best way forward. Such studies are in progress.

Topics: Antiemetics; Antineoplastic Agents; Female; Humans; Indoles; Male; Middle Aged; Nausea; Serotonin Antagonists; Tropisetron; Vomiting

A multicentre study was performed at four oncology centres in Sweden, in 160 chemotherapy-naive women, primarily with ovarian or endometrial carcinomas. Abdominal surgery preceded chemotherapy in 146 (91%) women, and another 39 (24%) women had a history of radiotherapy. The chemotherapy regimens contained cisplatin (50-100 mg/m2), in combination with a variety of other agents. In Course 1, all patients received tropisetron (5 mg i.v. Day 1; 5 mg p.o. Days 2-6) and 84% of patients achieved total or partial control of vomiting; 95% of patients achieved total or partial control of nausea during the first 24 hours. Vomiting was least successfully controlled on Day 2 (73% total or partial control) and Days 2-4 for the control of nausea (81, 83, 88% total or partial control, respectively). Patients with partial response in Course 1 (39% of patients) were randomized to addition of dexamethasone or placebo in Course 2. In Course 2, tropisetron plus dexamethasone (Group B2) prevented acute vomiting in 75% of patients, compared with 40% of patients receiving tropisetron plus placebo (Group B1). Over the entire 6 days, there was no vomiting at all in 54% and 20% of B2 and B1 patients, respectively. In Course 2, acute nausea was prevented in 75% of patients (receiving B1) and in 37% of patients (receiving B2). For nausea, over the complete 6 days, the figures were 64% and 3% (p < 0.001). This indicated that patients with incomplete control of emesis in Course 1 benefited from the addition of dexamethasone, provided that it was added for each of the 6 days studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Cisplatin; Dexamethasone; Drug Therapy, Combination; Female; Humans; Indoles; Middle Aged; Nausea; Serotonin Antagonists; Tropisetron; Vomiting

The efficacy of tropisetron, a new 5-HT3 receptor antagonist, was evaluated in a group of 15 children with a variety of malignant tumours. The majority of children (14/15) received fractionated chemotherapy and on day one complete control of acute nausea and vomiting was observed in 68.7% of all patients with a single, 15-minute, i.v. infusion of tropisetron. Partial control of vomiting was observed in 25% of patients and of nausea in 31.3% of patients on Day 1. Complete control of delayed nausea and vomiting was more variable, with an observed range between 50%-81% of patients over Days 2-6. There was no loss of appetite in 75% of patients treated with tropisetron on Day 1 and, more variably, in 62%-87% of patients on Days 2-6. Side effects were recorded in 18.8% of chemotherapy cycles, the most significant being insomnia in 12.5% of cycles and slight fever in 6.3% of cycles. It was concluded that tropisetron was well suited for children and could be recommended for those receiving a high burden of fractionated chemotherapy.

Topics: Adolescent; Antiemetics; Antineoplastic Agents; Child; Child, Preschool; Female; Humans; Indoles; Male; Nausea; Serotonin Antagonists; Tropisetron; Vomiting

An open, non-comparative, Nordic multicenter study was performed during 1991-1992 to evaluate the new 5-HT3 receptor antagonist tropisetron, as an antiemetic agent in various types of cancer chemotherapy. More than 600 patients were recruited from 16 cancer centers in Sweden, Finland and Denmark. In this report an interim analysis on 231 patients is presented. Gynecological cancers (61%), lung cancer (14%) and breast cancer (7%), were the main diagnoses. In 118 of 231 patients (51%) prior experience of chemotherapy was documented. In 91 patients (39%) cisplatin was part of the cytostatic regimen. Carboplatin (27%), doxorubicin (32%), epidoxorubicin (18%) were also frequently included. In all, 18 cytostatic agents were studied. The median number of courses studied was 3.3 (range 1-15). Overall 153 of 231 patients (67%) were completely protected from acute nausea and vomiting during the first course of chemotherapy. Delayed nausea and vomiting (Days 2-6) were completely controlled in 45%-72%. Treatment efficacy remained stable (57%-89%) over 10 consecutive courses of chemotherapy. For non-cisplatin regimens complete protection was achieved in 78% compared with 51% for cisplatin-regimens (p < 0.0001). Patients with no prior experience of chemotherapy had greater control of acute nausea and vomiting (73%) than patients treated before (61%) in the first course, but not in subsequent courses. There were no such differences in control of delayed nausea and vomiting between chemotherapy-naive and previously treated patients. Sex and age were significant prognostic factors with regard to antiemetic response. Adverse events were recorded in 19%-36% of the cases during long-term follow-up. Headache (16%) and constipation (5%) were most frequent.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Female; Humans; Indoles; Male; Middle Aged; Nausea; Scandinavian and Nordic Countries; Serotonin Antagonists; Tropisetron; Vomiting

166 patients receiving moderately emetogenic chemotherapy were entered into a randomised prospective study in which the efficacy of single dose ondansetron 8 mg, tropisetron 5 mg and granisetron 3 mg in the prophylaxis of acute vomiting was evaluated. 130 patients were evaluable for analysis. During the 24 h following the start of chemotherapy complete control of vomiting was achieved in 80% [95% confidence interval (CI) 73.1; 86.9] of patients receiving granisetron compared with 75% (95% CI 67.1; 82.1) of those on tropisetron and 69% (95% CI 60.5; 76.5) on ondansetron. The patients experienced significantly fewer failures with granisetron (6.2%, 95% CI 2.1; 10.3) than with either ondansetron (14.6%, 95% CI 8.5; 20.6) or tropisetron (13.8%, 95% CI 7.9; 19.7). When asked, 34 (26%) patients out of 130 expressed no preference, 54 (42%) preferred granisetron, 22 (17%) preferred ondansetron and 20 (15%) preferred tropisetron. All the 5-HT3 receptor antagonists were highly effective in the prophylaxis of acute vomiting induced by moderately emetogenic chemotherapy. The observed differences in the control of emesis, although statistically significant, may not have clinical significance.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Female; Granisetron; Humans; Indoles; Male; Middle Aged; Neoplasms; Ondansetron; Patient Satisfaction; Prospective Studies; Receptors, Serotonin; Serotonin Antagonists; Tropisetron; Vomiting

Nausea and vomiting are among the most frequent and severe acute side-effects of cytotoxic therapy and are not optimally controlled by conventional antiemetics. This situation warrants the evaluation of new classes of antiemetic agents such as the 5-HT3 receptor antagonists. 19 children with a median age of 9 years (range 2-16 years), treated with cytotoxic drug combinations that had previously caused nausea and vomiting refractory to conventional antiemetics, were given the selective 5-HT3 receptor antagonist ICS 205-930. The drug was given intravenously (i.v.) at 0.2 mg/kg (maximum 5 mg) during the chemotherapy infusion period and was continued orally for up to 5 days in chemotherapy courses containing cisplatin. The number of emetic episodes was recorded and the response was scored according to following scale: grade 1 = no nausea, no emetic episode; grade 2 = up to four episodes of vomiting and less than 5 h of nausea; grade 3 = five or more than five emetic episodes and/or nausea for at least 5 h. The 19 patients received a total of 169 various courses of chemotherapy combined with ICS 205-930. A score of 3 was observed during one course only, a score of 2 in 37 out of the 169 courses, including the four courses with cisplatin. The drug was very well tolerated. Side-effects possibly related to ICS 205-930 were mild to moderate headache in 4 patients during seven courses overall and obstipation in 3 patients during 11 courses. The results strongly suggest that ICS 205-930 is a highly effective and safe antiemetic agent in non-naive pediatric patients receiving non-cisplatin cytotoxic chemotherapy and who had failed conventional antiemetic treatment.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Female; Humans; Indoles; Male; Nausea; Serotonin Antagonists; Tropisetron; Vomiting

In a multicentre trial, 78 patients with a variety of malignancies, who had experienced insufficient control of emesis (greater than or equal to 3 episodes within 24 hours) while receiving standard antiemetics during previous chemotherapy, were randomly assigned to receive tropisetron 5mg once daily for 5 days or conventional antiemetic drugs. No attempt was made to standardise the conventional antiemetic treatment, which was given according to the usual practice of the participating institutions. Emesis was evaluated by counting emetic episodes and nausea by asking the patients to record on a diary chart the duration and severity of the nausea. Emesis was much better controlled with tropisetron than with standard drugs, complete control during the first 24 hours being achieved in 42% and 8% of patients, respectively, (p less than 0.001). Nausea was of significantly shorter duration (6.9 vs 10.3 hours; p less than 0.01) and was less severe (p less than 0.005) in the tropisetron group. The patients' overall assessment of treatment outcome was markedly better for tropisetron than for the standard antiemetic therapy. The superior efficacy of tropisetron was especially marked during the first 24 hours. For delayed nausea, no significant difference between treatments was seen. No serious adverse effects were observed.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Female; Humans; Indoles; Male; Middle Aged; Nausea; Neoplasms; Tropisetron; Vomiting

The efficacy and tolerability of tropisetron in preventing cisplatin-induced nausea and vomiting was studied in 2 open trials and compared with the efficacy and tolerability of metoclopramide plus lorazepam in a randomised crossover trial. In the first study, tropisetron 10mg was administered intravenously over 15 minutes before the cisplatin infusion and a second 10mg dose was given after the 60-minute infusion of cisplatin (greater than 50 mg/m2) in 54 patients with advanced cancers, for a total of 165 courses. Good responses for nausea and vomiting were recorded in 83.0% and 87.9% of courses, respectively, with complete protection from nausea and vomiting in 44.8% and 66.1% of courses, respectively. In the second study in 25 patients whose characteristics and cisplatin schedule were comparable with those of the first study, very similar results were achieved in 104 courses of chemotherapy, despite a reduction in tropisetron dose to a single 5mg intravenous infusion 15 minutes before cisplatin. The efficacies of intravenous tropisetron 5mg and metoclopramide 2 mg/kg plus lorazepam administered 15 minutes before cisplatin in preventing acute and delayed nausea and vomiting were compared in a randomised crossover study involving 20 patients. Tropisetron was significantly superior (p less than 0.001) in controlling both acute and delayed (day 1) symptoms. In all studies, the tolerability of tropisetron was excellent. The most frequent side effect was mild to moderate headache, occurring in 5 to 7% of patients. In conclusion, our experience suggests that tropisetron is an effective and well tolerated antiemetic drug that improves the quality of life of cancer patients administered highly emetogenic chemotherapy regimens.

Topics: Adult; Aged; Antiemetics; Cisplatin; Female; Humans; Indoles; Lorazepam; Male; Metoclopramide; Middle Aged; Nausea; Neoplasms; Single-Blind Method; Tropisetron; Vomiting

Forty-seven patients receiving non-cisplatin-containing chemotherapy were entered in a prospective study in which the efficacy of ondansetron plus dexamethasone and tropisetron plus dexamethasone in the prophylaxis of acute vomiting was evaluated. Thirty-nine patients were evaluable for cross-over analysis. During the 24 hours following the start of chemotherapy, 97% of patients on ondansetron plus dexamethasone reported total control of vomiting compared with 82% of those on tropisetron plus dexamethasone (p = 0.026). Thus, both 5-HT3- receptor antagonists combined with dexamethasone were highly effective in controlling acute vomiting induced by non-cisplatin-containing chemotherapy. The observed difference between the treatments may be caused by different dose schedules of ondansetron and tropisetron. A double-blind design with equal number of placebo-controlled administrations is needed to ascertain whether there is a significant pharmacological difference between ondansetron and tropisetron.

Topics: Acute Disease; Adult; Aged; Antineoplastic Agents; Dexamethasone; Drug Therapy, Combination; Female; Humans; Indoles; Male; Middle Aged; Ondansetron; Serotonin Antagonists; Tropisetron; Vomiting

Tropisetron is a novel antiserotoninergic drug with potent and specific activity against cancer chemotherapy-induced emesis. High-dose cyclophosphamide or high-dose melphalan are chemotherapeutic regimens associated with severe nausea and vomiting refractory to current antiemetic medications. We compared in a randomised open label study the antiemetic efficacy of tropisetron and alizapride in a first group of 32 consecutive patients treated with high-dose alkylating agent chemotherapy with or without autologous bone marrow transplantation. Tropisetron was more effective than alizapride in reducing vomiting episodes. In the first 24 h of treatment the median number of episodes in patients treated with tropisetron was 5 compared with 9 episodes in the alizapride group (P = 0.005). In the 72 h study period the median number of emetic episodes was 6 in the tropisetron group and 12 in the alizapride group (P = 0.004). In a second group of 26 consecutive patients, a combination of tropisetron plus haloperidol, a dopamine antagonist, was employed for prevention of emesis. This combination was more effective than tropisetron as single agent in preventing emetic episodes, as the median number of emetic episodes in the 72 h of observation was only 3, while they were 6 in the tropisetron group. The side-effects of tropisetron were mild and reversible upon discontinuation of the drug. We conclude that tropisetron is an effective antiemetic drug when employed in high-dose alkylating agent chemotherapy, and that its activity is potentiated by the association with haloperidol.

Topics: Adult; Antiemetics; Antineoplastic Agents; Drug Therapy, Combination; Haloperidol; Humans; Indoles; Injections, Intravenous; Middle Aged; Nausea; Pyrrolidines; Random Allocation; Tropisetron; Vomiting

The results of an open study designed to evaluate the prevention of cisplatin-induced emesis by the specific 5-HT3 receptor antagonist ICS 205-930 are reported. Fifty-four cancer patients, treated with diverse chemotherapy regimens, all including cisplatin (greater than = 50 mg/m2), received ICS 205-930 for a total of 165 courses. ICS 205-930 (10 mg) was given i.v. immediately before the cisplatin infusion and a second 10-mg dose was given immediately after. In 109 courses (66%) the patients did not have any vomiting episodes. Nausea was absent in 44.8% of courses. More than 3 vomiting episodes occurred only in 17 (10.4%) courses, and severe nausea only in 11 (6.6%). ICS 205-930 was extremely well tolerated. Mild headache occurred during 7 courses (4.2%) in 4 patients, hypotension during 5 courses (3%) in 3 patients and lipothymia in 2 courses (1.2%) in 2 patients. These results suggest that ICS 205-930 is an effective and well tolerated antiemetic drug in patients receiving cisplatin chemotherapy.

Topics: Adult; Aged; Cisplatin; Drug Evaluation; Female; Humans; Indoles; Male; Middle Aged; Nausea; Neoplasms; Tropisetron; Vomiting

Topics: Antiemetics; Apoptosis; Down-Regulation; Humans; Melanoma; Molecular Docking Simulation; NF-kappa B; Ondansetron; Paclitaxel; Serotonin; Tropisetron; Vomiting

Topics: Antiemetics; Humans; Tropisetron; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is common in patients with lymphoma and multiple myeloma (MM) receiving high-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT). Despite a standard triple antiemetic regimen of a neurokinin-1 (NK1) receptor antagonist (RA), a 5-hydroxytryptamine-3 (5-HT3) RA, and dexamethasone is recommended, how to control the protracted CINV in ASCT setting remains an intractable problem. Here, we retrospectively analyze CINV data of 100 patients who received either SEAM (semustine, etoposide, cytarabine, melphalan) or MEL140-200 (high-dose melphalan) before ASCT, evaluate the efficacy and safety of multiple-day administration of fosaprepitant combined with tropisetron and olanzapine (FTO), and compare the results to those of patients who received a standard regimen of aprepitant, tropisetron, and dexamethasone (ATD). The overall rate of complete response (CR), defined as no emesis and no rescue therapy, is 70% in the FTO group compared to 36% in the ATD group. Although CR rates are comparable in the acute phase between the two groups, significantly more patients treated by FTO achieve CR in the delayed phase than those treated by ATD (74% vs. 38%, p < 0.001). Moreover, FTO treatment significantly reduced the percentage of patients who are unable to eat, as well as the requirement for rescue medications. Both regimens are well tolerated and most adverse events (AEs) were generally mild and transient. In conclusion, the antiemetic strategy containing multiple-day administration of fosaprepitant is safe and effective for preventing CINV in lymphoma and MM patients, particularly in the delayed phase.

Topics: Antiemetics; Antineoplastic Agents; Dexamethasone; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma; Melphalan; Morpholines; Multiple Myeloma; Nausea; Olanzapine; Retrospective Studies; Transplantation Conditioning; Transplantation, Autologous; Tropisetron; Vomiting

To evaluate the efficacy and toxicity of palonosetron for prevention of vomiting induced by high dose cisplatin-based chemotherapy.. One-hundred and twenty-eight patients received tropisetron 5 mg plus dexamethasone 10 mg at the first cycle or palonosetron 0.25 mg plus dexamethasone 10 mg, respectively, each administered 30 min before the initiation of high dose cisplatin-based chemotherapy. To observe the remission rate of acute emetic episodes and delayed emetic episodes, adverse effects and daily food-intake in the patients after the chemotherapy.. The complete response (CR) rates for acute vomiting were not significantly different between the tropisetron and palonosetron cycles (75.8% vs. 79.7%, P>0.05). The complete control rate of delayed vomiting in the palonosetron cycle was significantly higher than that in the tropisetron cycle (70.3% vs. 50.8%, P<0.01). The food-intake decrease rate of palonosetron cycle was 18.8%, significantly lower than the 53.1% of the tropisetron cycle (P<0.05). The toxicity in the two cycles was similar and no grade 3-4 toxicity was observed.. Palonosetron is superior to tropisetron with a lower remission rate of delayed emesis induced by high dose cisplatin-based chemotherapy and with tolerable toxicity. Moreover, the apparent emesis control of palonosetron treatment seems to provide an adequate food-intake in these patients.

Topics: Aged; Antiemetics; Antineoplastic Agents; Cisplatin; Eating; Female; Humans; Indoles; Isoquinolines; Male; Middle Aged; Neoplasms; Palonosetron; Quinuclidines; Tropisetron; Vomiting

Significant electrophysiological and biochemical findings suggest that receptor cross-talk occurs between serotonergic 5-HT(3)- and tachykininergic NK(1)-receptors in which co-activation of either receptor by ineffective doses of their corresponding agonists (serotonin (5-HT) or substance P (SP), respectively) potentiates the activity of the other receptor to produce a response. In contrast, selective blockade of any one of these receptors attenuates the increase in abdominal vagal afferent activity caused by either 5-HT or SP. This interaction has important implications in chemotherapy-induced nausea and vomiting (CINV) since 5-HT(3)- and NK(1)-receptor antagonists are the major classes of antiemetics used in cancer patients receiving chemotherapy. The purpose of this study was to demonstrate whether the discussed interaction produces effects at the behavioral level in a vomit-competent species, the least shrew. Our results demonstrate that pretreatment with either a 5-HT(3) (tropisetron)- or an NK(1) (CP99,994)-receptor specific antagonist, attenuates vomiting caused by a selective agonist (2-methyl 5-HT or GR73632, respectively) of both emetic receptors. In addition, relative to each antagonist alone, their combined doses were 4-20 times more potent against vomiting caused by each emetogen. Moreover, combined sub-maximal doses of the agonists 2-methyl 5-HT and GR73632, produced 8-12 times greater number of vomits relative to each emetogen tested alone. However, due to large variability in vomiting caused by the combination doses, the differences failed to attain significance. The antiemetic dose-response curves of tropisetron against both emetogens were U-shaped probably because larger doses of this antagonist behave as a partial agonist. The data demonstrate that 5-HT(3)- and NK(1)-receptors cross-talk to produce vomiting, and that synergistic antiemetic effects occur when both corresponding antagonists are concurrently used against emesis caused by each specific emetogen.

Topics: Analysis of Variance; Animals; Antiemetics; Dose-Response Relationship, Drug; Drug Synergism; Female; Indoles; Male; Neurokinin-1 Receptor Antagonists; Peptide Fragments; Piperidines; Receptors, Neurokinin-1; Serotonin; Serotonin 5-HT3 Receptor Antagonists; Shrews; Substance P; Tropisetron; Vomiting

Nausea and vomiting are relatively common in advanced cancer and is dreaded more than pain by patients. The history, pattern of nausea and vomiting, associated symptoms, and physical examination provides clues as to etiology and may guide therapy. Continuous severe nausea unrelieved by vomiting is usually caused by medications or metabolic abnormalities, while nausea relieved by vomiting or induced by eating is usually due to gastroparesis, gastric outlet obstruction, or small bowel obstruction. Drug choices are empiric or based on etiology. Metoclopramide has the greatest evidence for efficacy followed by phenothiazines and tropisetron. Corticosteroids have not been effective in randomized trials except in the case of bowel obstruction. Treatment of nausea unresponsive to first-line medications involves rotation to medications which bind to multiple receptors (broad-spectrum antiemetics), the addition of another antiemetic to a narrow-spectrum antiemetic (a serotonin receptor antagonist such as tropisetron to a phenothiazine), rotation to a different class of antiemetic (tropisetron for a phenothiazine), or in-class drug rotation. Venting gastrostomy, octreotide, and corticosteroids will reduce nausea and vomiting associated with malignant bowel obstruction.

Topics: Algorithms; Antiemetics; Causality; Decision Trees; Drug Therapy, Combination; Evidence-Based Medicine; Gastroparesis; Gastrostomy; Humans; Indoles; Intestinal Obstruction; Medical History Taking; Metoclopramide; Nausea; Neoplasms; Patient Selection; Physical Examination; Research Design; Serotonin Antagonists; Tropisetron; Vomiting

5-HT3 receptor antagonists (e.g. tropisetron) combined with dexamethasone are effective for the acute phase of cisplatin (CIS)-induced emesis. This study determined the possible additive or synergistic antiemetic efficacy of Delta9-THC when combined with tropisetron or dexamethasone (DEX). Delta9-THC (0-10 mg/kg i.p.) was injected in combination with tropisetron (0-5 mg/kg i.p.) or dexamethasone (0-20 mg/kg i.p.) prior to CIS (20 mg/kg i.p.) in the least shrew, and the induced emesis was recorded for 60 min. CIS-induced vomiting was dose-dependently and significantly attenuated by individual administration of Delta9-THC (59-97% reductions) and tropisetron (79-100% attenuation), but not dexamethasone (26-40%), although a trend (p<0.1) towards reduced vomiting frequency following DEX was noted. Low doses of Delta9-THC (0.25 or 0.5 mg/kg) when combined with low doses of tropisetron (0.025, 0.1, or 0.25 mg/kg) were more efficacious in reducing emesis frequency than when given individually, but Delta9-THC had no antiemetic interactions with DEX. However, no tested combination provided a significantly greater effect on the number of animals vomiting than their individually-administered counterparts. The modest interaction of Delta9-THC with tropisetron suggests they activate overlapping antiemetic mechanisms, while the lack of interaction with dexamethasone needs further clarification.

Topics: Animals; Antiemetics; Antineoplastic Agents; Cisplatin; Dexamethasone; Dose-Response Relationship, Drug; Dronabinol; Female; Indoles; Male; Shrews; Tropisetron; Vomiting

The aim of this study was to estimate interindividual differences in the antiemetic effects of 5-HT(3) receptor antagonists by evaluating the influence of pharmacokinetics on 5-HT(3) receptor occupancies, based on receptor occupancy theory.. We analyzed interindividual differences of 5-HT(3) receptor occupancies and antiemetic effects after the oral and/or intravenous administration of standard doses of the following 5-HT(3) receptor antagonists: azasetron, granisetron, indisetron, ondansetron, ramosetron, and tropisetron.. The interindividual difference between maximum and minimum 5-HT(3) receptor occupancies after oral administration ranged from 0.6% to 64.0%, and that difference after intravenous administration ranged from 0.6% to 29.6%. Following oral administration, the interindividual difference between maximum and minimum complete vomiting inhibition rates ranged from 0.2% to 16.1%. After intravenous administration, that difference ranged from 0.8% to 52.5%.. Interindividual differences in the clinical effects of 5-HT(3) receptor antagonists could be evaluated based on receptor occupancy theory, and the differences varied among drugs. Drug selection considering these individual variations might be useful for the patients who experienced vomiting associated with chemotherapy.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Bridged Bicyclo Compounds, Heterocyclic; Drug Administration Schedule; Granisetron; Humans; Indoles; Models, Theoretical; Ondansetron; Oxazines; Serotonin 5-HT3 Receptor Antagonists; Treatment Outcome; Tropisetron; Vomiting

Even though significant progress has been made, chemotherapy-induced emesis remains a challenging problem. Few studies focus on emesis in patients treated with carboplatin and the observation period is limited to the initial 24 h following chemotherapy. Thus, we investigated if tropisetron (T) monotherapy can adequately prevent acute and delayed emesis in non-small-cell lung cancer (NSCLC) patients receiving a moderately emetogenic chemotherapy (MEC) (carboplatin-containing) regimen. Furthermore, we explored the merits of adding dexamethasone (D) or alprazolam (A) to T, especially in the setting of a pre-existing high level of stress. We studied 60 patients with advanced NSCLC receiving carboplatin and taxanes in three consecutive cycles. During the first cycle, patients received 5 mg of T intravenously before chemotherapy and the same dose per os on each of the following 3 days. In the second cycle, T was co-administered with 8 mg of D once a day, while, during the third cycle, T was combined with per os A 0.25 mg every 12 h and continued over the following 3 days. Finally, we evaluated the impact of stress on the anti-emetic response achieved with the previously described regimens. The combination of T + A was superior to T monotherapy and the combination of T + D, regarding the prevention of acute and delayed emesis. Both T + A and T + D combinations led to appetite improvement, while patients receiving T + A experienced sedation more frequently. Interestingly, subgroup analysis revealed that patients without underlying stress obtained no further benefit by the addition of A or D, while both T + A and T + D combinations led to a better anti-emetic response in patients with stress. In conclusion, T monotherapy provides a satisfactory result in controlling nausea and emesis caused by a MEC regimen in patients without stress. However, the addition of D and, mainly, A improves its anti-emetic effect in patients with obvious stress.

Topics: Aged; Alprazolam; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Dexamethasone; Female; Humans; Indoles; Lung Neoplasms; Male; Middle Aged; Stress, Psychological; Taxoids; Treatment Outcome; Tropisetron; Vomiting

To establish the effectiveness of oral 5-HT(3) antagonist, oral 5 mg tropisetron was introduced in the 21 cases with hematological malignancies for the prevention of chemotherapy-induced nausea and vomiting. Nausea and vomiting did not develop in 81% of patients receiving the tropisetron in this study. The results suggested that oral tropisetron is effective for the control of acute, and to a lesser extent, delayed, nausea and vomiting. The drug enhanced patients' quality of life and reduced the clinical cost. In conclusion, tropisetron is effective for the prevention of chemotherapy-induced nausea and vomiting in treatment for hematological malignancies. It is suitable as first-line therapy for outpatients.

Topics: Administration, Oral; Adult; Aged; Antiemetics; Female; Hematologic Neoplasms; Humans; Indoles; Male; Middle Aged; Nausea; Tropisetron; Vomiting

Effective antiemetic therapy is crucial for patients undergoing chemotherapy or radiotherapy for cancer. Severe nausea and vomiting associated with such cancer treatment can lead to anxiety, anorexia, dehydration, electrolyte disturbance and renal failure, and may interrupt cancer therapy, demoralise patients or even cause them to abandon treatment. In 1992, we welcomed the introduction of ondansetron, the first selective serotonin type 3- (5HT3-) receptor antagonist marketed in the UK, as an important advance in preventing chemotherapy-induced nausea and vomiting. Several selective 5HT3-receptor antagonists are now licensed. They are widely prescribed to patients receiving cancer treatment, but not always appropriately. Here we review their optimal use.

Topics: Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Child; Granisetron; Humans; Indoles; Isoquinolines; Nausea; Neoplasms; Ondansetron; Palonosetron; Practice Guidelines as Topic; Quinolizines; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Tropisetron; Vomiting

Serotonin (5-hydroxytryptamine type 3 [5-HT3]) receptor antagonists have substantially reduced but not eliminated nausea and vomiting in patients undergoing cancer chemotherapy. They act through specific binding to the 5-HT3A, 5-HT3B receptor complex. The 5-HT3B subunit seems to be most important for its functionality. We hypothesized that patients with genetic variations in the 5-HT3B receptor gene might respond differently to antiemetic treatment.. We included 242 cancer patients on their first day of chemotherapy. Nausea and vomiting were documented before and twice during the chemotherapy using standardized interviews and visual analog scales. We sequenced the entire 5-HT3B receptor gene, including the 5' flanking region and at least a 20-base pair intronic sequence of each intron-exon splice site of all patients.. Approximately 30% of all patients suffered from nausea or vomiting. Sequencing of the 5-HT3B receptor gene revealed 13 polymorphisms: two of them were amino acid exchanges (Tyr129Ser, Ala223Thr) and two were deletion variants. In both observation periods, patients homozygous for the -100_-102delAAG deletion variant of the promotor region experienced vomiting more frequently than did all the other patients.. A more efficient antiemetic treatment with 5-HT3 receptor antagonists might be possible on a pharmacogenetic basis. However, only a small fraction of the therapeutic failure is explained by the -AAG deletion variant of the 5-HT3B receptor gene. Additional clinical and biochemical studies are needed to confirm the association.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Female; Gene Deletion; Germany; Humans; Indoles; Logistic Models; Male; Middle Aged; Neoplasms; Ondansetron; Polymorphism, Genetic; Prospective Studies; Receptors, Serotonin; Statistics, Nonparametric; Tropisetron; Vomiting

To clarify the mechanism for the severe emesis concomitant with intensive chemotherapy, we investigated the effects of 5-HT3- and 5-HT4-receptor antagonists on the emesis induced by the high-dose of cisplatin in Suncus murinus. The emesis induced by 50 mg/kg of cisplatin was reduced by the oral pretreatment with tropisetron, which is known as a 5-HT3- and 5-HT4-receptor dual antagonist in vitro, with the ID50 value of 0.52 mg/kg. On the contrary, granisetron, a selective 5-HT3-receptor antagonist, did not markedly inhibit the emesis at up to 30 mg/kg. Moreover, GR125487, a selective 5-HT4-receptor antagonist, did not inhibit the emesis. However, co-administration of GR125487 and granisetron significantly reduced the number of emetic episodes. The study of the co-administration of GR125487 with tropisetron showed that GR125487 did not further enhance the inhibitory effect of tropisetron alone, suggesting that the anti-emetic effect of tropisetron is mediated via the blockade of both 5-HT3 and 5-HT4 receptors. These results suggest that both the 5-HT3 and 5-HT4 receptors are involved in the emesis induced by the high-dose of cisplatin in Suncus murinus.

Topics: Animals; Antiemetics; Antineoplastic Agents; Cisplatin; Granisetron; Indoles; Male; Ondansetron; Receptors, Serotonin; Receptors, Serotonin, 5-HT3; Receptors, Serotonin, 5-HT4; Serotonin Antagonists; Shrews; Sulfonamides; Tropisetron; Vomiting

1. In SUNCUS: murinus the ultrapotent capsaicin analogue resiniferatoxin (RTX) induced an emetic response in the dose range 1 - 1000 microg kg(-1), s.c. The latency was inversely related to dose and ranged from 41.2+/-4.4 min. (1 microg kg(-1), s.c.) to 2.7+/-0.6 min. (1000 microg kg(-1), s.c.). 2. The emetic response to RTX (10 or 100 microg kg(-1), s.c.) was blocked or markedly reduced by pre-treatment with RTX (100 microg kg(-1), s.c.), 8-OH-DPAT (100 microg kg(-1), s.c.), morphine (2 mg kg(-1), s.c.), neonatal capsaicin (100 mg kg(-1), s.c.) and the NK(1) receptor antagonist CP-99,994 (10 - 20 mg kg(-1), s.c.) but not by the 5-HT(3) receptor antagonist tropisetron (200 microg kg(-1), s.c.). 3. RTX (100 microg kg(-1), s.c.) induced c-fos-like immunoreactivity in the area postrema and parts of the nucleus tractus solitarius. This pattern is consistent with the proposal that the emetic effect is mediated via one or both of these structures and an involvement of substance P is discussed. 4. RTX (10 and 100 microg kg(-1), s.c.) had broad-spectrum antiemetic effects in Suncus as indicated by its ability to block or markedly reduce the emetic response to motion (1 Hz, 4 cm lateral, 10 min.), cisplatin (20 mg kg(-1), i.p.), intragastric copper sulphate (40 mg kg(-1), p.o.), nicotine (10 mg kg(-1), s.c.) and RTX (100 microg kg(-1), s.c.) itself. 5. It is proposed that the site of the anti-emetic effect is in the nucleus tractus solitarius and mechanisms involving the modulation of substance P release are discussed. 6. The general utility of SUNCUS: for investigations of vanilloid receptors is reviewed in the light of the exquisite sensitivity of the emetic reflex in this species to resiniferatoxin.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Abdomen; Animals; Animals, Newborn; Antiemetics; Behavior, Animal; Capsaicin; Cisplatin; Copper Sulfate; Diterpenes; Dose-Response Relationship, Drug; Female; Indoles; Injections, Intraventricular; Male; Medulla Oblongata; Morphine; Motion Sickness; Nicotine; Piperidines; Proto-Oncogene Proteins c-fos; Serotonin Receptor Agonists; Shrews; Tropisetron; Vagotomy; Vomiting

The mechanism of induction of emesis by X-ray irradiation remains largely unknown. The purpose of the present research was to clarify the neuronal basis of the induction of nausea induced by X-ray irradiation analyzing c-Fos expression in the nucleus tractus solitarii (NTS) as a marker of cellular excitation. We confirmed that the dose of X-ray irradiation (4 Gy) used for the present research could actually induce nausea by preliminary measurement of kaolin intake. Induction of c-Fos immunoreactivity in the NTS was observed in the animals that received X-ray irradiation of the whole body. The mean number of c-Fos positive cells in the animals that received irradiation was significantly larger than that in the non-irradiated animals. Partial exposure of the abdomen to X-rays showed significantly greater c-Fos expression than that of the head. These results indicated the presence of a certain route for transmitting information from the periphery toward the central nervous system by X-ray irradiation. The number of c-Fos positive cells induced by X-ray irradiation in animals vagotomized at the subdiaphragmatic level was lower than that in sham-operated animals. Animals receiving a serotonin subtype three (5-HT3, 5-hydroxytryptamine) receptor antagonist (tropisetron, ICS 205-930, 3-tropanyl-indole-3-carboxylate) showed a significant reduction in c-Fos protein expression compared to animals receiving a vehicle. These results strongly suggested that X-ray irradiation activates 5-HT3 receptors on the terminals of the abdominal vagal nerves to excite the afferent pathway, thereby inducing emesis.

Topics: Abdomen; Animals; Indoles; Kaolin; Male; Nausea; Neurons; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Receptors, Serotonin; Receptors, Serotonin, 5-HT3; Serotonin Antagonists; Solitary Nucleus; Tropisetron; Vagus Nerve; Vomiting; X-Rays

Among the most distressing symptoms experienced by patients who have undergone high-dose chemotherapy and stem cell transplantation are nausea and vomiting. The chemotherapy regimens used in high-dose conditioning protocols are highly emetogenic. The 5HT3 receptor antagonists are very effective in the prevention and abolition of nausea and vomiting resulting from chemotherapeutic drugs. One of them, tropisetron, is a selective antagonist of serotonin 5HT3 receptors with proven efficacy against emesis. Dexamethasone is also known as an effective agent against nausea and vomiting. The addition of dexamethasone to a 5HT3 receptor antagonist is synergistic, as has been shown in many trials with highly emetogenic drugs. The aim of the present trial was to study the efficacy and safety profile of the combination of tropisetron and dexamethasone in controlling nausea and vomiting in patients receiving megatherapy prior to stem cell transplantation. We studied 31 patients. All of them were evaluable for response and toxicity. The majority of patients achieved complete or major protection against acute vomiting (71-83%), and 67-84% of the patients had no or mild nausea. The combination was tolerated well, and only a minority of patients reported side effects. Among them the most common were headache (in three patients) and constipation. No patient withdrew from the study because of toxicity. It has become evident from our data that the administration of 5 mg tropisetron daily in combination with 20 mg dexamethasone for 8 days can prevent the acute emesis otherwise experienced by patients receiving high-dose chemotherapy as conditioning in stem cell transplantation programmes.

Topics: Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Constipation; Dexamethasone; Drug Combinations; Drug Synergism; Female; Headache; Hematopoietic Stem Cell Transplantation; Humans; Indoles; Male; Middle Aged; Nausea; Neoplasms; Prospective Studies; Serotonin Antagonists; Transplantation Conditioning; Tropisetron; Vomiting

A prospective observational multicenter trial was carried out to assess the incidence, pattern, and prognostic factors of radiation-induced emesis (RIE), and evaluate the use of antiemetic drugs in radiation oncology clinical practice.. Fifty-one Italian radiation oncology centers took part in this trial. The accrual lasted 2 consecutive weeks, only patients starting radiotherapy in this period were enrolled. Exclusion criteria were age under 18 years, and concomitant chemotherapy. Evaluation was based on diary cards filled in daily by patients during radiotherapy and 1 week after stopping it. Diary cards recorded the intensity of nausea and any episode of vomiting and retching. Prophylactic and symptomatic antiemetic drug prescriptions were also registered.. Nine hundred thirty-four patients entered the trial, and 914 were evaluable. Irradiated sites were: breast in 211 patients, pelvis in 210 patients, head and neck in 136 patients, thorax in 129 patients, brain in 52 patients, upper abdomen in 42 patients, skin and/or extremities in 37 patients, and other sites in 97 patients. Vomiting and nausea occurred in 17.1% and 37.3% of patients, respectively, and 38.7 % patients had both vomiting and nausea. At multifactorial analysis, the only patient-related risk factor that was statistically significant was represented by previous experience with cancer chemotherapy. Moreover, two radiotherapy (RT)-related factors were significant risk factors for RIE, the irradiated site and field size. In fact, a statistically significant higher percentage of RIE was registered in upper abdomen RT and RT fields > 400 cm2. Although nonstatistically significant, patients receiving RT to the thorax and head and neck presented a higher incidence of RIE. Only a minority (14%) of patients receiving RT were given an antiemetic drug, and the prescriptions were more often symptomatic than prophylactic (9% vs. 5%, respectively). Different compounds and a wide range of doses and schedules were used; however, there is some evidence from our data that in spite of antiemetic prophylaxis, 46% of patients had vomiting, and 58% had nausea. The majority (93%) of the prophylactic group received oral 5-hydroxytriptamine receptor (5-HT3) antagonist (8 mg/day, 7 days/week). In the symptomatic group, 54% and 41% patients received 5-HT3 antagonists and metoclopramide, respectively. At multivariate analysis, no patient- or RT-related risk factor for RIE was found to influence significantly the prophylactic or symptomatic use of antiemetics.. Our study provided useful data on epidemiology and characteristics of RIE. Previous chemotherapy, field size, and irradiated site (upper abdomen) were the only significant prognostic factors of RIE. A remarkable incidence of RIE was found in patients submitted to thoracic and head and neck RT. With this background of knowledge, it will be possible to better plan further studies on this important problem. Moreover, the low rate of antiemetics use and the wide variety of doses and schedules employed suggest the need to reinforce the "evidence based" approach to identify the best antiemetic approach to RIE.

Topics: Adult; Antiemetics; Domperidone; Drug Administration Schedule; Female; Humans; Incidence; Indoles; Male; Metoclopramide; Middle Aged; Nausea; Ondansetron; Prognosis; Prospective Studies; Radiotherapy; Sex Factors; Time Factors; Tropisetron; Vomiting

To perform a cost-effectiveness analysis (CEA) between a standard antiemetic regimen-chlorpromazine + dexamethasone (CPM-DEX)- and a 5-HT3 receptor antagonist-tropisetron (TROP)--in the control of acute emesis induced by highly emetogenic chemotherapy in children, considering two analytic perspectives: hospital and patients.. The CEA was performed by constructing a decision tree, for both analytic perspectives, of the possible outcomes of treatment with TROP (single 0.2 mg/kg i.v.) or CPM (5-15 mg i.v. infusion for 3 doses) plus DEX (2 mg/m2 i.v. bolus i.v. x2). The patients were stratified by age in two groups (2-12 and 13-17). To estimate the probability of each endpoint at the decision tree we have taken as a base a trial developed in the Department of Pediatrics. Direct medical cost of primary therapy, failure, complications and side effects were included in the cost calculations.. From patients' analytic perspective, TROP was more cost-effective than CPM-DEX for both groups of patients. Discrepancy between both analytic perspectives in 13-17 year-old patient's group was resolved in favour of the option chosen from the patients' analytic perspective (TROP). Sensitivity analysis showed the reliability of the results.. 1. TROP was more cost-effective than CPM-DEX. 2. Taking into account the patients' analytic perspective is essential when we compare antiemetics pharmacoeconomically. 3. It seems necessary to increase the effectiveness of TROP in pediatric patients receiving highly emetogenic chemotherapy with strategies such as the addition of a steroid.

Topics: Adolescent; Age Factors; Antiemetics; Child; Child, Preschool; Chlorpromazine; Cost-Benefit Analysis; Dexamethasone; Humans; Indoles; Sensitivity and Specificity; Tropisetron; Vomiting

Tropisetron is a novel selective antagonist of the type-3 serotonin (5-HT3) receptor, with proven efficacy in the control of emesis related to cancer treatment. Epirubicin in doses of > 100 mg/m2 has a high emetogenic potential. This study was designed to determine whether a single intravenous administration of tropisetron could prevent acute nausea and vomiting in patients treated with high dose epirubicin. Forty chemotherapy naive breast cancer patients treated with epirubicin at a dose of 110 mg/m2 on an outpatient basis were enrolled in the study. Tropisetron 5 mg i.v. was used as antiemetic prophylaxis. "On demand" treatment with tropisetron 5 mg p.os was used for the rescue of patients who failed on the initial i.v. dose. Complete control of acute nausea and vomiting had 62.5% (95% C.I. 47.2-77.8), partial control 15% (95% C.I. 3.8-26.2) and 22.5% (95% C.I. 9.3-35.7) insufficient control or failure. Headache was the most common adverse event reported in 3 patients (7.5%) and constipation in 2 patients (5%). Interestingly, patients with a negative experience of nausea and vomiting during pregnancy and those treated for metastatic disease, had a better control of chemotherapy-induced nausea and vomiting. In conclusion, a single 5 mg i.v. dose of tropisetron is safe and effective in preventing acute emesis in patients treated with high dose epirubicin.

Topics: Acute Disease; Adult; Aged; Antibiotics, Antineoplastic; Antiemetics; Breast Neoplasms; Chemotherapy, Adjuvant; Combined Modality Therapy; Constipation; Epirubicin; Female; Granulocyte Colony-Stimulating Factor; Headache; Humans; Indoles; Injections, Intravenous; Middle Aged; Nausea; Treatment Outcome; Tropisetron; Vomiting

The aim of this manuscript is to introduce Cryptotis parva (the least shrew) as a new experimental emesis model. The chemotherapeutic agent, cisplatin, caused a dose-dependent increase in the number of animals exhibiting vomiting and retching behaviours with ED50 values of 6.43+/-1 and 7.9+/-1.2 mg/kg, respectively. The frequencies of these parameters were also dose-dependent. Intraperitoneal administration of 5-HT3 receptor antagonists (tropisetron or MDL 72222) prevented cisplatin-induced emesis and retching behaviours in the least shrew by a dose-dependent mechanism with respective ID50 values of 4.28+/-2.8 and 2.05+/-2 for emesis, and 2.71+/-4.5 and 2.52+/-2.59 for retching. Intraperitoneal injection of selective and nonselective 5-HT3 receptor agonists potently, and in a dose-dependent fashion, induced emesis in the least shrew with the following ED50 potency order: 2-methyl 5-HT approximately 5-HT (p > 0.05) <5-HTQ (p < 0.01)

Topics: Analysis of Variance; Animals; Antiemetics; Antineoplastic Agents; Cisplatin; Creatinine; Dose-Response Relationship, Drug; Drug Combinations; Female; Indoles; Male; Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; Shrews; Tropanes; Tropisetron; Vomiting

Ethanol-induced emesis were investigated using Suncus murinus and the emetogenic mechanisms of ethanol were compared with those of cisplatin. Intraperitoneal injection of ethanol caused dose-dependent emesis with ED50 value of 22.3% (v/v) when injection volume was adjusted to 4 ml/kg. Intraperitoneal and subcutaneous injection of acetaldehyde also caused dose-dependent emesis (ED50 = 3.5% (v/v) with an extremely shorter latency (6% i.p.: 1.0 +/- 0.3 min cf. 40% ethanol: 13.0 +/- 1.9 min). Neither ethanol nor acetaldehyde caused emetic responses when injected intracerebroventricularly. Pretreatment with disulfiram, an inhibitor of liver aldehyde dehydrogenase, potentiated the emetogenic effects of ethanol. Surgical abdominal vagotomy, which blocks cisplatin-induced emesis completely, did not prevent ethanol-induced emesis. 5-HT3 receptor antagonists, which also cause complete inhibition of cisplatin-induced emesis, did not affect the responses. However, ethanol-induced emesis was prevented by the pretreatment with 8-hydroxy-2-(di-n-propylamino)tetrarin hydrobromide (8-OH-DPAT) and N-(2-mercaptopropionyl)-glycine (MPG) dose-dependently. The tackykinin NK1 receptor antagonist (+)-(2S, 3S)-3-(2-methoxybenzylamino)-2-phenyl-piperidine (CP-99,994) also attenuated ethanol-induced emesis. Taken together, these results suggest that 1) acetaldehyde is probably responsible for ethanol-induced emesis, 2) active site for ethanol maybe peripheral, 3) ethanol-induced emesis is mediated by free radicals, and 4) mechanism of ethanol-induced emesis and that caused by cisplatin are different in many respects, although in some they are similar and that the precise pathways remain to be identified. Therefore, the tolerance to emetogenic effects of cisplatin in alcoholic patients cannot be explained as a simple cross desensitization of the pathway.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Acetaldehyde; Alcohol Deterrents; Animals; Antiemetics; Baclofen; Benzamides; Bridged Bicyclo Compounds, Heterocyclic; Central Nervous System Depressants; Disulfiram; Dose-Response Relationship, Drug; Ethanol; Female; GABA Antagonists; Indoles; Injections, Intraperitoneal; Injections, Intraventricular; Injections, Subcutaneous; Male; Piperidines; Serotonin Antagonists; Serotonin Receptor Agonists; Shrews; Tiopronin; Tropisetron; Vagotomy; Vomiting

Topics: Antiemetics; Antineoplastic Agents; Drug Costs; Granisetron; Humans; Indoles; Nausea; Ondansetron; Serotonin Antagonists; Tropisetron; Vomiting

Topics: Antiemetics; Antineoplastic Agents; Child; Humans; Indoles; Infant; Nausea; Tropisetron; Vomiting

The ability of three cardiac glycosides, ouabain, digitonin and digitoxin, to induce emesis and their mechanism(s) of action were investigated in Suncus murinus. The intraperitoneal injection of ouabain but not digitonin nor digitoxin caused vomiting in a dose-dependent manner. However, the administration of ouabain into the cerebroventricle did not cause emesis. Ouabain-induced emesis was partly prevented by surgical abdominal vagotomy. Pretreatment with tropisetron, a selective 5-HT3 (5-hydroxytriptamine) receptor antagonist, did not affect the emetic response evoked by ouabain. These results suggest that ouabain exerts emetic effects via peripheral mechanism(s), but 5-HT3 receptors are not involved in the pathway.

Topics: Animals; Antiemetics; Cardiac Glycosides; Digitonin; Digitoxin; Female; Indoles; Injections, Intraperitoneal; Injections, Intraventricular; Male; Ouabain; Receptors, Serotonin; Receptors, Serotonin, 5-HT3; Serotonin Antagonists; Shrews; Tropisetron; Vagotomy; Vomiting

In order to elucidate possible male/female differences in emesis, the effects of various emetogenic drugs (cisplatin, copper sulfate, veratrine, nicotine, serotonin) and motion stimulus were compared between male and female Suncus murinus. Cisplatin (IP), nicotine (SC), veratrine (SC) and copper sulfate (PO) induced dose-dependent emesis in either sex, and there was no apparent difference in estimated ED50 values. However, male animals tended to be more susceptible to serotonin-induced emesis. The ID50 values for tropisetron, a 5-HT3 receptor antagonist, to block serotonin-induced emesis were also similar between male and female animals. However, tropisetron was less effective against cisplatin-induced emesis in females. Therefore, cisplatin may release more serotonin to induce emesis in females. Reciprocal shaking (horizontal oscillation 40 mm, frequency 0.5 to 2.0 Hz, duration 5 min) induced more frequent emesis in male animals, and the latency to the first vomit was shorter in males than in females. These results suggest that there is substantial sex-dependent difference in the emetic responses and male animals are in general more susceptible. These results are discussed in the light of similar studies in man.

Topics: Animals; Antiemetics; Cisplatin; Copper Sulfate; Female; Indoles; Male; Motion Sickness; Nicotine; Receptors, Serotonin; Receptors, Serotonin, 5-HT3; Serotonin; Serotonin Antagonists; Sex Factors; Shrews; Tropisetron; Veratrine; Vomiting

Efficacy and safety of the antiemetic agent Navoban (5HT3-receptor-antagonist Tropisetron) on cytostatic-induced emesis of breast cancers and gynecological cancers was tested in 28 female patients receiving a total of 127 chemotherapy courses containing high (cisplatin), moderate high (cyclophosphamid) or moderate (for example 5 FU) emetogenic cytostatic drugs. We studied antiemetic response rates of Navoban (5 mg/d) during the first 24 hours after administration of the chemotherapy as well as response rates of the "delayed nausea and emesis" (days 2-9 after chemotherapy). A complete response was observed in 103 chemotherapy courses (= 81.1%) during the first 24 hours after chemotherapy and in 93 courses (= 73.2%) for the "delayed emesis". Treatment failures (more than 5 vomiting episodes) during the first 24 hours were present in four courses and for the "delayed emesis" in 11 courses. The side effects of Navoban such as constipation, headache or tiredness were minimum. Therefore no patient refused to receive the necessary chemotherapy. Navoban is, with its single dose application, an effective therapeutic drug for the prevention of nausea and emesis in patients receiving a chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Genital Neoplasms, Female; Humans; Indoles; Middle Aged; Nausea; Palliative Care; Serotonin Antagonists; Tropisetron; Vomiting

In the course of treatment for tumors and recurrences, 86 children, aged 4-16 years, received polychemotherapy which induced excessive vomiting. Navoban (tropisetron) was administered to control vomiting. Total or partial control of nausea and vomiting was observed in 94.1%. No side-effects were registered.

Topics: Adolescent; Antiemetics; Antineoplastic Agents; Child; Child, Preschool; Female; Humans; Indoles; Male; Nausea; Treatment Outcome; Tropisetron; Vomiting

The administration of platinum-based chemotherapy induces serotonin release from the enterochromaffin cells, causing nausea and vomiting. This study was conducted to evaluate parameters of serotonin metabolism following platinum-based chemotherapy given in combination with the serotonin type-3 antagonist tropisetron as an antiemetic agent. In nine chemotherapy-naive patients with disseminated germ-cell tumors, parameters of serotonin metabolism in both blood and urine were evaluated during two consecutive courses of platinum-based chemotherapy. Serotonin concentrations in platelet-rich plasma and platelet-poor plasma as well as urinary 5-hydroxyindoleacetic acid (5-HIAA) and serotonin levels were measured during the full length of the courses. By means of comparison with the antiemetic agent chlorpromazine, used on day 1 of the first course only, the effect of the serotonin type-3 antagonist tropisetron, the antiemetic agent used during the rest of the courses, on these parameters was studied. Clinical effects were also recorded. No change in the parameters of serotonin metabolism could be demonstrated during either course by the serotonin type-3 antagonist tropisetron. Also in vitro, no effect of tropisetron on the active serotonin uptake by platelets was found. Serotonin levels in platelets showed no correlation with emetic response. However, the platelet serotonin content decreased significantly between the first and the second course (P < 0.01). The significant reduction in platelet serotonin content observed between the first and the second course indicates a depletion of total body serotonin. The role of a serotonin type-3 antagonist might be affected by the altered serotonin equilibrium during later courses of chemotherapy.

Topics: Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Chlorpromazine; Cisplatin; Drug Interactions; Etoposide; Humans; Hydroxyindoleacetic Acid; Indoles; Infusions, Intravenous; Neoplasms, Germ Cell and Embryonal; Serotonin; Serotonin Antagonists; Tropisetron; Vomiting

Tropisetron (Navoban, Sandoz Pharma Ltd., Basel, Switzerland), a selective antagonist of the serotonin receptor (5-HT3) dosed once-daily at 0.2 mg/kg (with a maximum of 5 mg daily), was evaluated in the prevention of chemotherapy-induced nausea and vomiting in 131 children with a median age of 5 years (age 10 weeks to 21 years). Acute lymphocytic leukemia was the most common malignancy (49%). Most children (82%) had received cytotoxic chemotherapy before enrollment. Patients received tropisetron during one or more courses of chemotherapy (455 courses in total). Tropisetron was administered slowly intravenously as a single dose before the start of chemotherapy on day 1 and intravenously or by mouth the subsequent days as a single daily dose (median treatment duration: 5 days). Response to tropisetron per 24 hour period on the first 5 days of each chemotherapy course was graded as complete (absence of both nausea and vomiting), partial (one to four vomits and/or less than 5 hours of nausea), or failure. Overall complete response on day 1 was observed in 305 out of 455 chemotherapy courses (67%). The patients receiving intravenous chemotherapy (N = 92) had a 70% complete response rate and a 26% partial response rate on day 1, both for course 1 and course 2. The percentage of complete responders increased the subsequent days of the course. Emesis after day 1 was observed primarily during courses with the most emetogenic chemotherapy. No side-effects of tropisetron other than a single case of diarrhoea were documented in this study.

Topics: Adolescent; Adult; Antiemetics; Antineoplastic Agents; Child; Child, Preschool; Female; Humans; Indoles; Infant; Male; Nausea; Tropisetron; Vomiting

A prospective trial was performed to better assess the risk of nausea and vomiting and the rescue value of tropisetron (TRO), a 5-HT3 receptor antagonist, in 88 patients undergoing fractionated radiotherapy to the abdomen or to large supradiaphragmatic fields and failing a first anti-emetic trial with metoclopramide (MET). Nausea was graded 0 (absent), 1 (mild), 2 (moderate) and 3 (severe). Nausea requiring anti-emetics (> or = grade 2) was present in 64% of the patients. MET was able to control nausea (< or = grade 1) in 26 of 58 patients (45%) who developed > or = grade 2 nausea during radiation treatment (2 patients vomiting without nausea included). 34 patients required TRO, and 31 experienced immediate relief. However, nausea (> or = grade 2) recurred in 7 patients from 1 to 3 weeks after starting TRO. Sex, age, field type and field size (cm2) did not influence the incidence and severity of nausea and vomiting. Only 24/88 patients vomited after starting radiotherapy. MET helped to eliminate emesis in one third of these patients. TRO helped to control vomiting in 73% of the salvaged patients. Constipation was observed in 8 patients on TRO and was a reason to stop the medication in 4 cases.

Topics: Abdominal Neoplasms; Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Child; Female; Humans; Indoles; Male; Metoclopramide; Middle Aged; Nausea; Prospective Studies; Tropisetron; Vomiting

Topics: Antiemetics; Clinical Trials as Topic; Humans; Indoles; Nausea; Neoplasms; Serotonin Antagonists; Tropisetron; Vomiting

We evaluated the antiemetic efficacy of tropisetron, a 5-HT3 receptor antagonist, during its compassionate use in children with malignant disease who during previous chemotherapy cycles experienced emesis refractory to metoclopramide-based treatments.. Tropisetron was given to 15 children (eight boys and seven girls 18 months to 18 years of age) with miscellaneous neoplasms. Generally 5 mg/day of tropisetron was administered i.v. the first day of cisplatin-based chemotherapy and i.v. or orally each subsequent day of chemotherapy. The dose of tropisetron was reduced to 2 mg/day in children < 2 years of age and weighing < 20 kg.. Vomiting was well controlled (no more than two episodes per day) on 118 of the 184 days of treatment with tropisetron (64%). No clinically important variations were observed in blood pressure, heart rate, body temperature, or electrocardiographic findings attributable to tropisetron. Transient, mild to moderate side effects (headache, constipation, abdominal pain, diarrhea) occurred in five patients on 11 of the 184 days of tropisetron treatment (6%).. The results obtained during compassionate use of tropisetron confirm that it is a valid, safe, and manageable antiemetic for the treatment of pediatric patients.

Topics: Adolescent; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Child; Female; Humans; Indoles; Infant; Male; Metoclopramide; Neoplasms; Serotonin Antagonists; Tropisetron; Vomiting

The involvement of visceral afferent fibers and 5-HT3 or 5-HT4 receptors in the vomiting induced by oral administration of copper sulfate was investigated in beagle dogs. Vomiting induced by copper sulfate (100 mg/kg) was inhibited markedly by bilateral abdominal vagotomy and bilateral greater splanchnic nerve section. The vomiting induced by copper sulfate was inhibited by blocking 5-HT4 receptors with high doses (1 and 3 mg/kg, i.v.) of ICS 205-930. On the other hand, blocking 5-HT3 receptors with MDL 72222 (0.5 and 5 mg/kg, i.v.) or low doses (0.01 mg/kg i.v.) of ICS 205-930 had no apparent effect on the vomiting induced by copper sulfate. Oral administration of a 5-HT4 receptor agonist, 5-methoxytryptamine (5-MT), caused vomiting at a dose of 100 mg/kg, and the vomiting was inhibited markedly by abdominal visceral nerve section or a high dose (1 mg/kg, i.v.), but not a low dose (0.01 mg/kg, i.v.), of ICS 205-930. Intravenous administration of 5-MT (10 mg/kg) failed to induce vomiting. These results suggest that the abdominal visceral afferent fibers and possibly peripheral 5-HT4 receptors play an important role in the vomiting induced by oral administration of copper sulfate in dogs.

Topics: 5-Methoxytryptamine; Administration, Oral; Animals; Copper; Copper Sulfate; Dogs; Female; Indoles; Injections, Intravenous; Male; Nerve Fibers; Receptors, Serotonin; Serotonin Antagonists; Splanchnic Nerves; Tropanes; Tropisetron; Vagotomy; Viscera; Vomiting

Topics: Antiemetics; Antineoplastic Agents; Humans; Indoles; Nausea; Neoplasms; Serotonin Antagonists; Tropisetron; Vomiting

Topics: Antiemetics; Antineoplastic Agents; Child; Humans; Indoles; Nausea; Serotonin Antagonists; Tropisetron; Vomiting

Several series of N-(quinuclidin-3-yl)aryl and heteroaryl-fused pyridones were synthesized and evaluated for 5-HT3 receptor affinity. In the heteroaryl series, 2-(quinuclidin-3-yl)tetrahydropyrido-[4,3-b]indol-1-one (8a) and the 4,5-alkano-bridged analogues (14 and 15) displayed high 5-HT3 receptor affinity with pKi values > 9. The (3S)-quinuclidinyl isomers had > 10 fold higher affinity than the (3R)-isomers. In a series of 2-quinuclidin-3-yl)isoquinolin-1-ones, derivatives substituted with small lipophilic groups (25b-e) and with 4,5-alkano-bridges (34-36) also displayed high affinity. In particular, the hexahydro-1H-benz[de]isoquinolinone (S,S)-37 was the highest affinity 5-HT3 receptor ligand prepared (pKi 10.4). A number of the high affinity ligands were shown to be potent 5-HT3 receptor antagonists in vivo as determined by inhibition of the B-J reflex in the anesthetized rat. Again, (S,S)-37 was the most active agent tested (ID50 0.02 microgram/kg i.v.), and this compound was also potent in blocking cisplatin-induced emesis in both the ferret and the dog. Computer modeling studies were performed, and previously reported 5-HT3 receptor antagonist pharmacophore models were refined to include a key lipophilic binding domain.

Topics: Animals; Cisplatin; Computer Simulation; Dogs; Ferrets; Isoquinolines; Male; Models, Molecular; Molecular Structure; Palonosetron; Pyridones; Quinuclidines; Rats; Rats, Sprague-Dawley; Receptors, Serotonin; Serotonin Antagonists; Stereoisomerism; Structure-Activity Relationship; Vomiting

Topics: Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Child; Cisplatin; Cyclophosphamide; Dactinomycin; Drug Evaluation; Humans; Indoles; Oropharyngeal Neoplasms; Remission Induction; Tropisetron; Vinblastine; Vomiting

Topics: Animals; Antiemetics; Antineoplastic Agents; Humans; Indoles; Nausea; Serotonin Antagonists; Tropisetron; Vomiting

The participation of free radicals in cisplatin-induced emesis was investigated in the house musk shrew, Suncus murinus. Thiobarbituric acid (TBA) values, which indicate the degree of lipid peroxidation, in brain, liver and small intestine were increased significantly 60 min after the treatment with cisplatin (20 mg/kg, i.p.). Moreover, cisplatin (20 mg/kg, i.p.)-induced emesis was prevented by intraperitoneal injection of N-(2-mercaptopropionyl)glycine (MPG), a radical scavenging agent, with ID50 value of 130 mg/kg. However, MPG did not block the emesis induced by copper sulfate (40 mg/kg, p.o.), veratrine (0.5 mg/kg, s.c.) or serotonin (10 mg/kg, i.p.). We also investigated the effects of superoxide dismutase conjugated to polyethylene glycol and catalase, but the number of vomiting episodes and latency did not change significantly when these agents were intraperitoneally injected 30 min prior to or 20 min after the administration of cisplatin. MPG did not affect the antitumor effect of cisplatin tested in vitro. These results suggest that free radicals mediate emesis caused by cisplatin and that radical scavengers may become a new class of prophylactic drug against cancer-chemotherapeutic drug-induced emesis.

Topics: Animals; Antineoplastic Agents; Brain; Cisplatin; Female; Free Radical Scavengers; Free Radicals; Gastric Mucosa; Indoles; Intestine, Small; Kidney; Lipid Peroxidation; Liver; Shrews; Thiobarbiturates; Tiopronin; Tropisetron; Tumor Cells, Cultured; Vomiting

The emetic effects of copper sulfate and cisplatin and the potential involvement of vagal afferent fibers and 5-HT3 receptors in the emesis were investigated in cynomolgus monkeys. Retching and vomiting induced by both oral (100 mg/kg) and intravenous (20 mg/kg) copper sulfate were inhibited markedly by abdominal vagotomy. Furthermore, the emetic response induced by oral copper sulfate was strongly inhibited by intravenous ICS 205-930 (0.1 mg/kg), a 5-HT3 receptor antagonist. Cisplatin (3 mg/kg, i.v.) caused severe retching and vomiting, and the number of emetic responses was much greater than that in other species. The emetic response induced by cisplatin was inhibited markedly by abdominal vagotomy or concurrent administration of ICS 205-930 (3 x 0.1 mg/kg, i.v.). These results suggest that the monkey is more sensitive to cisplatin than other species and that the vagal afferent terminals and 5-HT3 receptors play an important role in the emetic response induced by copper sulfate and cisplatin.

Topics: Administration, Oral; Animals; Cisplatin; Copper; Copper Sulfate; Female; Indoles; Injections, Intravenous; Macaca fascicularis; Neurons, Afferent; Receptors, Serotonin; Serotonin Antagonists; Tropisetron; Vagotomy; Vagus Nerve; Vomiting

Topics: Adolescent; Adult; Antiemetics; Drug Evaluation; Drug Tolerance; Humans; Indoles; Leukemia; Tropisetron; Vomiting

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Drug Evaluation; Female; Humans; Indoles; Male; Nausea; Neoplasms; Tropisetron; Vomiting

X-irradiation-induced emesis was investigated in Suncus murinus, a house musk shrew. Whole body X-irradiation caused emesis, and the calculated ED50 value that induced emesis in 50% of animals was 429 cGy. At the irradiation dose of 800 cGy all the animals vomited 10.0 +/- 2.4 times with a latency of 20.0 +/- 2.9 min. The emetogenic effect of X-irradiation was dependent on the part of the body exposed. Abdominal X-irradiation at 1000 cGy caused emesis in all animals studied, whereas the same dose to the head had no emetogenic effect. We investigated several prophylactic methods against X-irradiation-induced emesis. Surgical vagotomy completely inhibited the emesis induced by 800 cGy X-irradiation. Emesis was also prevented by the subcutaneous administration of tropisetron (ICS 205-930, a selective serotonergic 5-HT3 receptor antagonist) with an ID50 value of 29 micrograms/kg. These results suggest that (1) suncus is a useful experimental animal for the study of radiation-induced emesis and the development of prophylactic drugs, (2) serotonin plays an important role in X-irradiation-induced emesis, and (3) X-irradiation-induced emesis is very similar to that caused by cancer chemotherapeutic agents.

Topics: Animals; Antiemetics; Female; Indoles; Shrews; Tropisetron; Vagotomy; Vomiting; Whole-Body Irradiation

Tropisetron is a 5-HT3 receptor antagonist which suppresses nausea and vomiting induced by cancer chemotherapeutic agents. In this study, tropisetron was evaluated on a compassionate-need basis in 545 cancer patients who had either proved refractory to antiemetic treatment during previous chemotherapy or who were at high risk of emesis as a result of current therapy. Tropisetron (5 mg or 10 mg) was administered as a 15-minute infusion prior to chemotherapy, with the further possibility of an additional dose, either orally or parenterally, on one or more subsequent days. In some patients the drug was administered orally on the day before treatment. On Day 1 of Course 1, 64.7% of patients had a complete response to tropisetron, i.e. no nausea or vomiting, and 26.9% of patients had a partial response. More than 80% of patients with a complete response in Course 1 had a complete response in Course 2 and of the partial responders in Course 1, 37% achieved a complete response in Course 2. Of the 7.6% failures in Course 1, a further 26% achieved a complete response in Course 2. Tropisetron was well tolerated, with adverse effects recorded in only 45 (8%) patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Child; Child, Preschool; Female; Humans; Indoles; Male; Middle Aged; Nausea; Serotonin Antagonists; Tropisetron; Vomiting

Topics: Antiemetics; Antineoplastic Agents; Female; Granisetron; Humans; Indoles; Male; Ondansetron; Receptors, Serotonin; Serotonin Antagonists; Tropisetron; Vomiting

Tropisetron (ICS 205-930) antagonizes the serotonin type 3 receptor and has antiemetic activity in animals given cisplatin. Its mean serum half-life in 11.1 hours.. In this dose-ranging trial, 22 patients undergoing anti-cancer chemotherapy received 24 courses of a single intravenous infusion of tropisetron beginning 30 minutes before chemotherapy. Four dose levels were explored (range, 12-48 mg/m2).. Toxicities were mild and included headache, transient elevations of serum alanine transaminase and/or aspartate transaminase levels, and sedation. No akathisia or acute dystonic reactions were observed. Thirty-six percent of patients had no emesis, and 58% had two or fewer emetic episodes. Ten patients received high-dose cisplatin (dose, > or = 100 mg/m2) as initial chemotherapy. Of these, 30% had no emesis, and 60% had two or fewer episodes.. Tropisetron can be administered safely in the doses tested with no dose-limiting toxicities. The encouraging antiemetic efficacy, mild toxicities, lack of extrapyramidal effects, and convenience of a single 15-minute infusion regimen make this drug appropriate for study in additional trials.

Topics: Adult; Aged; Antineoplastic Agents; Female; Humans; Indoles; Infusions, Intravenous; Male; Middle Aged; Serotonin Antagonists; Tropisetron; Vomiting

The efficacy of tropisetron in the prevention of nausea and vomiting induced by chemotherapy of varying emetogenic potential was evaluated in 545 patients with a variety of malignancies who had either proved refractory to antiemetic treatment during previous chemotherapy courses or who were considered to be at high risk of nausea and vomiting. Tropisetron 5 or 10mg was administered intravenously just before chemotherapy, with the possibility of additional oral or intravenous doses on the day before chemotherapy and on 1 or more subsequent days. On day 1 of the first course of chemotherapy, a complete response (no nausea and no vomiting) was achieved in 62% of patients and a partial response (1 to 4 vomits and/or episodes of nausea) in 29%. Among the 325 patients who received a second course of chemotherapy, more than 80% of those with a complete response on day 1 of course 1 also had a complete response on day 1 of course 2; 37% and 26%, respectively, of patients with a partial response or failure (1 or more vomits and/or episodes of nausea) on day 1 of course 1 then had a complete response on day 1 of course 2.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Child; Child, Preschool; Drug Resistance; Female; Humans; Indoles; Male; Middle Aged; Nausea; Neoplasms; Tropisetron; Vomiting

Oral tropisetron, a 5-hydroxytryptamine type 3 (serotonin3) [5-HT3]-receptor antagonist, at a dose of 5mg daily was evaluated as antiemetic prophylaxis during postoperative abdominal irradiation. 20 women with International Federation of Gynecology and Obstetrics (FIGO) stage I to III ovarian carcinoma were included. 12 women received irradiation of whole abdominal fields and 8 of lower abdominal/pelvic fields. Efficacy and adverse events were recorded by the patients in diary-form booklets. The cumulative weekly incidence of patients with nausea, which was generally mild and of short duration, increased from 30% at the start of radiotherapy to 54% at the end of treatment. Episodes of vomiting occurred in less than 10% of the patients. Diarrhoea was common towards the end of the radiotherapy courses, and the proportion of patients needing extra antidiarrhoeal medication (loperamide) increased from 38% during the first week to 100% at the end of the radiotherapy course. Mean weight loss was 1.2kg during the 5- to 6-week course. Overall ratings for quality of life were excellent or good in 75 to 85% of patients. Tropisetron seems to be a promising and well tolerated drug in conjunction with extended radiotherapy of abdominal fields. This was an open study, establishing the methodology for long term follow-up of patients during fractionated radiotherapy.

Topics: Adult; Aged; Antiemetics; Diarrhea; Female; Humans; Indoles; Middle Aged; Nausea; Ovarian Neoplasms; Quality of Life; Radiation Injuries; Tropisetron; Vomiting

The involvement of visceral afferent fibers and 5-HT3 receptors in the emesis induced by cisplatin was studied in beagle dogs. The emesis induced by cisplatin (3 mg/kg, i.v.) was inhibited by the intravenous administration of ICS205930 (2 x 0.01 or 2 x 0.1 mg/kg) and MDL72222 (2 x 0.5 mg/kg), 5-HT3 receptor antagonists, but not by the intravenous administration of metoclopramide (2 x 0.5 mg/kg), a dopamine D2 receptor antagonist. The cisplatin-induced emesis was also suppressed by the intravenous administration of para-chlorophenylalanine (300 mg/kg/day for 3 days), an inhibitor of 5-HT synthesis. On the other hand, the administration of ICS205930 into the IVth ventricle (2 x 0.01 mg/animal) had no effects on the cisplatin-induced emesis. The cisplatin-induced emesis was completely inhibited by abdominal vagotomy and splanchnicectomy, but not by splanchnicectomy alone. On the contrary, the emesis induced by apomorphine was suppressed by the intravenous (0.1 mg/kg) or intracerebroventricular (0.05 mg/animal) administration of metoclopramide, but not by visceral nerve section. These results strongly suggest that cisplatin evokes emesis mainly by acting on the vagal afferent terminals through the release of 5-HT and that peripheral 5-HT3 receptors are involved in this action.

Topics: Afferent Pathways; Animals; Cisplatin; Dogs; Female; Indoles; Male; Metoclopramide; Receptors, Serotonin; Serotonin Antagonists; Tropanes; Tropisetron; Vagus Nerve; Vomiting

Tropisetron, a 5-HT3 receptor antagonist, was evaluated as antiemetic prophylaxis during postoperative abdominal irradiation of ovarian carcinoma patients. Twenty consecutive women with Stages I-III (FIGO) epithelial ovarian carcinomas were included. At the start of radiotherapy all patients were clinically tumor-free. Twelve women received irradiation on whole-abdominal fields, 1.0 Gy per fraction, during 6 weeks. Eight women were irradiated on the lower abdomino-pelvic fields, 1.7 Gy per fraction, during 5 weeks. Efficacy and adverse events were recorded by the patients in diary-form booklets using visual analog scales (VAS). All patients completed the treatment series and none was lost to follow-up. Nausea, generally mild (mean 20 mm VAS) and of short duration, increased from start (30%) to end of radiotherapy (54%). Episodes of vomiting were few in number and occurred in less than 10% of the cases. Diarrhoea was common towards the end of the radiotherapy courses, especially when the dose per fraction was 1.7 Gy and the need for extra antidiarrhoeal medication (loperamide) increased from 38% at the start to 100% at the end. The mean weight loss was only 1.2 kg during 5-6 weeks. The overall ratings for quality of life were excellent or good in 75-85% of the cases. The efficacy of tropisetron was rated excellent or good in 80% of the cases and the tolerability likewise in 85% in the overall evaluation of the drug made by the investigator. Tropisetron therefore seems to be a promising and well-tolerated drug in conjunction with extended radiotherapy on the whole- or lower-abdominal fields.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adult; Aged; Diarrhea; Evaluation Studies as Topic; Female; Follow-Up Studies; Humans; Indoles; Middle Aged; Nausea; Ovarian Neoplasms; Pilot Projects; Quality of Life; Radiotherapy; Serotonin Antagonists; Tropisetron; Vomiting

Tropisetron, a 5-HT3 receptor antagonist, was evaluated as antiemetic prophylaxis during postoperative abdominal irradiation of ovarian carcinoma patients. Twenty consecutive women with stages I-III (FIGO) epithelial ovarian carcinomas were included. Nausea, generally mild and of short duration, increased from start (30%) to end of radiotherapy (54%). Episodes of vomiting were few in number and occurred in less than 10% of the cases. Diarrhea was common toward the end of the radiotherapy courses. The overall ratings for quality of life were excellent or good in 75-85% of the cases. Tropisetron seems to be a promising and well-tolerated drug in conjunction with extended radiotherapy.

Topics: Abdomen; Antiemetics; Combined Modality Therapy; Female; Humans; Indoles; Neoplasm Staging; Ovarian Neoplasms; Ovariectomy; Postoperative Period; Serotonin Antagonists; Tropisetron; Vomiting

Previous studies of the mechanism of zacopride-induced emesis in ferrets have concluded that it is mediated predominantly by an antagonist effect on 5-HT3 receptors although the possibility of a contribution from an agonist effect at 5-HT4 receptors was not excluded. This study shows that zacopride (200 micrograms/kg p.o.)-induced emesis can be blocked by a 'high dose' (1000 micrograms/kg) of ICS205930 but not by a low dose (100 micrograms/kg) or by 'high doses' (1000 micrograms/kg) of another more selective 5-HT3 receptor antagonist granisetron. As ICS205930, at high doses, is reported to be a 5-HT4 receptor antagonist it appears likely that activation of 5HT4-receptors contributes to emesis induced by zacopride. 'High' doses of ICS205930, but not granisetron or ondansetron, can also block the vagally mediated emesis induced by oral CuSO4 suggesting that 5-HT4 receptors involved in emesis are closely associated with abdominal vagal afferents.

Topics: Analysis of Variance; Animals; Antiemetics; Benzamides; Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Copper; Copper Sulfate; Female; Ferrets; Granisetron; Imidazoles; Indazoles; Indoles; Loperamide; Male; Ondansetron; Receptors, Serotonin; Serotonin Antagonists; Tropisetron; Vomiting

Despite a number of significant advances over the past decade, prevention and treatment of chemotherapy-induced emesis remain formidable problems, particularly with cisplatin-containing regimens. Nearly one third of patients receiving high-dose cisplatin still experience substantial emesis despite the best available conventional antiemetics, and the toxic effects of these agents remain quite troublesome. In recent years, a new class of agents, the serotonin antagonists, has been identified. These agents hold promise for clinical utility in a wide range of areas. Selective antagonists of the serotonin (5-hydroxytryptamine) type 3 (5-HT3) receptor have proven in early clinical trials to be potent antiemetic agents in patients receiving cytotoxic chemotherapy, with efficacy comparable to or superior to that of conventional antiemetics. Toxic effects to date with the 5-HT3 receptor antagonists have been modest. The current state of knowledge with respect to these agents as antiemetics for patients receiving cytotoxic chemotherapy is summarized.

Topics: Antiemetics; Benzamides; Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Granisetron; Humans; Imidazoles; Indazoles; Indoles; Metoclopramide; Ondansetron; Quinolizines; Receptors, Serotonin; Serotonin Antagonists; Tropanes; Tropisetron; Vomiting

The racemate and (+)- and (-)-isomers of fenfluramine (5 mg kg-1 i.p., 1 h pretreatment) antagonized cisplatin-induced retching and vomiting in the ferret. The intravenous injection of (+/-)-fenfluramine administered on an established cisplatin-induced emesis antagonized the response within minutes of injection. The administration of a lower dose of (+/-)-fenfluramine (1.0 mg kg-1 i.p., 1 h pretreatment) failed to antagonize cisplatin-induced emesis when administered alone but enhanced the antiemetic effects of metoclopramide and ICS 205-930. This pretreatment with (+/-)-fenfluramine failed to enhance the antiemetic effects of zacopride. It is considered that an action of the racemate on presynaptic 5-HT/catecholaminergic systems to reduce neurotransmitter release may enhance the action of certain 5-HT3 receptor antagonists in controlling emesis induced by cisplatin.

Topics: Animals; Antiemetics; Cisplatin; Fenclonine; Fenfluramine; Ferrets; Indoles; Male; Metoclopramide; Reserpine; Serotonin Antagonists; Stereoisomerism; Tropisetron; Vomiting

The intravenous injection of cisplatin (10 mg/kg), the subcutaneous injection of apomorphine (0.125-1 mg/kg) and lisuride (0.001-0.1 mg/kg), the oral administration of ipecacuanha (0.3-2.4 mg/kg) and the intragastric administration of copper sulphate (25-100 mg/kg), induced a vomiting and retching response in the ferret. Pretreatment with dl-fenfluramine (5 mg/kg i.p.) prevented or reduced the emesis induced by cisplatin, apomorphine, ipecacuanha and lisuride but failed to significantly antagonise copper sulphate-induced emesis. The 5-HT3 receptor antagonist ICS 205-930 (0.1 mg/kg i.p.) prevented emesis induced by cisplatin and ipecacuanha but failed to prevent or significantly reduce the emesis induced by apomorphine, lisuride or copper sulphate. Dopamine receptor antagonists, including fluphenazine (0.1-1.0 mg/kg i.p.) prevented apomorphine- and lisuride-induced emesis but were less potent or had inconsistent actions to antagonise cisplatin- or ipecacuanha-induced emesis and failed to inhibit the emesis induced by copper sulphate. The data indicate that dopamine and/or 5-HT3 receptor systems are involved in drug-induced emesis but that emesis caused by gastric irritation induced by copper sulphate is mediated by different receptor mechanisms.

Topics: Animals; Apomorphine; Cisplatin; Copper; Copper Sulfate; Emetics; Female; Fenfluramine; Ferrets; Fluphenazine; Indoles; Ipecac; Lisuride; Male; Stereoisomerism; Tropisetron; Vomiting

The well-documented 5-HT3 receptor antagonists, ICS 205-930 and GR38032F, have been compared with regard to their inhibitory activity at 5-HT3 receptors to another gastrokinetic agent, zacopride. Zacopride and ICS 205-930 showed similar affinity (-log kB approximately 8.0), whereas GR38032F showed lower affinity (-log ka approximately 7.0) at 5-HT3 receptors in the guinea pig ileum. After i.v. administration to anesthetized rats, zacopride was approximately 10-fold more potent than either ICS 205-930 or GR38032F, which were equipotent as inhibitors of serotonin-induced bradycardia (5-HT3-mediated activation of the von Bezold Jarisch reflex). After oral administration to anesthetized rats, zacopride remained approximately 10-fold more potent than ICS 205-903, which was approximately 2-fold more potent than GR38032F as an inhibitor of serotonin-induced bradycardia. Furthermore, the inhibitory effectiveness of GR38032F persisted for less than 3 hr after oral administration and for less than 15 min after intravenous administration. ICS 205-930 produced maximal inhibition of serotonin-induced bradycardia for over 3 hr with heart rate returning to control values 6 hr after oral administration. Zacopride possessed the longest duration of inhibitory effectiveness in urethane-anesthetized rats with maximal inhibition still apparent 6 hr after oral administration. All three agents inhibited cisplatin-induced emesis after i.v. administration in dogs with zacopride being 10-fold more potent than ICS 205-930 or GR38032F, which were equipotent. These comparative data with three 5-HT3 receptor antagonists indicate that in animals, zacopride was more potent and longer acting than either ICS 205-930 or GR38032F. Furthermore, after oral administration to rats, GR38032F was slightly less potent than ICS 205-930 and possessed the shortest duration of action.

Topics: Animals; Benzamides; Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Bridged-Ring Compounds; Carbachol; Cisplatin; Guinea Pigs; Heart Rate; Imidazoles; In Vitro Techniques; Indoles; Male; Ondansetron; Receptors, Serotonin; Serotonin Antagonists; Tropisetron; Vomiting

5-Hydroxytryptamine3 antagonists have been reported to prevent emesis elicited by cisplatin and radiation. This study investigated the possibility that drugs with this mechanism of action may be useful in preventing emesis elicited by other stimuli. The drugs ICS 205-930 (0.1 and 1.0 mg/kg) and MDL 72222 (0.1 and 1.0 mg/kg) were administered SC to cats before challenging them with either provocative motion or an emetic dose of xylazine. In no instance was a significant reduction in emesis evident. Zacopride was also administered before motion testing (0.01 to 10.0 mg/kg) and found to not have efficacy. To test the possibility that species or route of administration were factors in the negative results, 1.0 mg/kg of ICS 205-930 was administered SC before IV infusion of 7.5 mg/kg of cisplatin. There was a total suppression of emesis for the duration of the six-hour observation periods. This result verifies other work which found 5-hydroxytryptamine3 antagonists to be effective in preventing emesis elicited by cancer chemotherapeutic treatments. However, there is no evidence that they are effective in other syndromes, such as motion sickness and xylazine-induced emesis.

Topics: Animals; Antiemetics; Benzamides; Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Cats; Cisplatin; Indoles; Motion Sickness; Receptors, Serotonin; Serotonin Antagonists; Thiazines; Tropanes; Tropisetron; Vomiting; Xylazine

Topics: Adult; Aged; Cisplatin; Female; Humans; Indoles; Male; Middle Aged; Nausea; Serotonin Antagonists; Tropisetron; Vomiting

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Female; Humans; Indoles; Male; Middle Aged; Pilot Projects; Serotonin Antagonists; Tropisetron; Vomiting

Topics: Antiemetics; Humans; Imidazoles; Indoles; Ondansetron; Receptors, Serotonin; Serotonin Antagonists; Tropisetron; Vomiting

The administration to the ferret of cisplatin, 10mg/kg (i.v.), caused an intense emetic response that was prevented by ICS 205-930 (0.1 and 1.0 mg/kg i.v.) and metoclopramide (4.0 mg/kg i.v.). Smaller doses of ICS 205-930 (0.01 mg/kg i.v.) and metoclopramide (2.0 mg/kg i.v.) attenuated the emetic response to cisplatin. It is concluded that the potent action of ICS 205-930 against cisplatin-induced emesis is the consequence of a 5-hydroxytryptamine M-receptor antagonism which may also contribute to the antiemetic action of metoclopramide.

Topics: Animals; Antiemetics; Cisplatin; Ferrets; Indoles; Male; Metoclopramide; Receptors, Serotonin; Tropisetron; Vomiting