tropisetron and Neoplasms

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

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

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

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

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 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

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

Severe nausea and vomiting are common and one of the most feared side effects of cisplatin-based chemotherapy. A total of 106 patients were randomized to receive a single dose of 8 mg ondansetron or 3 mg granisetron or 5 mg tropisetron intravenously as prevention of cisplatin-induced acute nausea and vomiting. Antiemetic therapy was done within 30 minutes before initiating chemotherapy. A questionnaire evaluating nausea, vomiting and retches was administered to patients and the responses were categorized as complete, partial or failure. The response determination was repeated in the first 24 hours, and within 24-72 hours following cisplatin administration. The complete response rates for ondansetron, granisetron and tropisetron in the first 24 hours were 51.4%, 65.7% and 61.1% respectively. All three agents were highly effective against cisplatin-induced acute and late vomiting and the results were statistically significant. This study demonstrated no significant difference in effectiveness of these three antiemetics. 5-HT3 (5-hydroxytryptamine 3) receptor antagonists have similar efficacy in the prevention of nausea and vomiting due to cisplatin. Thus, we recommend that drug choice be based on cost-benefit and patient tolerance.

Topics: Adult; Antiemetics; Antineoplastic Agents; Cisplatin; Cost-Benefit Analysis; Female; Granisetron; Humans; Indoles; Injections, Intravenous; Male; Middle Aged; Nausea; Neoplasms; Ondansetron; Treatment Outcome; Tropisetron; Vomiting, Anticipatory

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

We aimed to assess the potency and efficacy of tropisetron, a 5-HT3 receptor antagonist, in the prevention of nausea and emesis observed in the pediatric patient population taking various chemotherapy protocols.. Tropisetron (Navoban) was given to 100 children (62 boys and 38 girls aged 6 months to 15 years) with various malignancies. Patients received tropisetron during one or more courses of emetogenic chemotherapy for a total of 350 courses administered intravenously or intravenously and intrathecally. Tropisetron (0.2 mg/kg/day, maximum: 5 mg/day) was administered as a single intravenous dose slowly, before the start of chemotherapy on day 1 and intravenously or by mouth on subsequent days (median treatment duration: 5 days).. The patients receiving cytotoxic chemotherapy had a 70% complete response rate and a 24% partial response rate during the first 24 h period of the first course. We observed headache (five courses), diarrhea (three courses) and loss of appetite (one course) as side-effects (2.5%).. Tropisetron is safe, effective, easy to use, has no serious side-effects and can be recommended for pediatric patients. The efficacy of tropisetron may be enhanced by the addition of corticosteroids in patients receiving highly emetogenic cancer chemotherapy.

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

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

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

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

(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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The 5-hydroxytryptamine 3 receptor antagonists, including tropisetron, ondansetron, granisetron, and dolasetron are agents used effectively for supportive care. They are used for the prevention and treatment of chemotherapy and radiotherapy-induced emesis. Despite their overall excellent safety profile, some electrocardiographic changes related to heart rate and repolarization were reported. Ondansetron, granisetron, and dolasetron were studied on this manner. But to our knowledge, there is no information about the cardiac side effects of tropisetron. In this study, we aimed to determine the acute effects of tropisetron on ECG parameters related to repolarization, heart rate, and systemic blood pressure.. Fifty-five cancer patients who received tropisetron for the prevention of acute chemotherapy-induced nausea and vomiting were enrolled into this single center, prospective study. Standard 12-lead ECG recordings were performed at baseline and 30 min after tropisetron (5 mg given over 1 min IV bolus) administration. P wave durations and corrected QT intervals were measured; P wave dispersion and QTc dispersion were calculated.. In comparison with baseline, mean heart rate significantly decreased 30 min after administration of tropisetron. Tropisetron did not result in a significant change in P wave duration, corrected QT interval, P dispersion, and QTc dispersion.. In this study, tropisetron did not show any ventricular and atrial arrhythmogenic effect because of repolarization abnormalities. Only it may cause a slight decrease in heart rate.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Cardiotoxins; Cardiovascular Diseases; Cardiovascular System; Electrocardiography; Female; Heart Rate; Humans; Indoles; Male; Middle Aged; Neoplasms; Pilot Projects; Tropisetron

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

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

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

Topics: Antiemetics; Antineoplastic Agents; Humans; Indoles; Neoplasms; Tropisetron

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

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

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

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

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