tropisetron and Diarrhea

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 efficacy and tolerability of tropisetron were studied in an open trial comprising a total of 30 patients with advanced non-small cell lung cancer undergoing high-dose, cisplatin-based chemotherapy (cisplatin dosage 100 mg/m2). Patients received tropisetron 5 mg intravenous infusions for 15 min on day 1. followed by 5 mg tropisetron taken orally in the morning on days 2 6. All treated patients were assessed during the entire treatment period (6 days). Acute nausea and vomiting were evaluated during the 24 h after chemotherapy. Delayed nausea and vomiting were evaluated during days 2-6 after chemotherapy. Response to tropisetron was graded as: complete control, major control, minor control and failure for nausea or vomiting. Rates for complete plus major control of acute nausea and vomiting in cycles 1-5 were 77%, 81%, 86%, 67% and 75%, respectively. Rates for complete plus major control of delayed nausea and vomiting in cycles 1-5 were 87%, 76%, 86%, 78% and 75%, respectively. Adverse reactions were mainly headache and diarrhea, but both reactions were mild and are common in most patients treated with this type of antiemetic agent. It is concluded that tropisetron is an effective drug for the prevention of side effects of highly emetogenic drugs such as cisplatin. The dosage and schedule of tropisetron reported here can prevent both acute and delayed nausea and vomiting.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Cisplatin; Diarrhea; Female; Headache; Humans; Indoles; Lung Neoplasms; Male; Middle Aged; Nausea; Treatment Outcome; Tropisetron; Vomiting, Anticipatory

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

Topics: Adult; Aged; Diarrhea; Double-Blind Method; Female; Humans; Indoles; Male; Middle Aged; Radiotherapy; Serotonin Antagonists; Treatment Failure; Tropisetron

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

A 69-yr-old man with known carcinoid syndrome treated with octreotide and interferon-alpha 2b developed diarrhea, with six to eight watery to semiliquid stools per day. Diminished stool frequency and increased stool consistency were obtained by treatment with the 5-hydroxytryptamine-3 receptor antagonists ondansetron and tropisetron. Successful alleviation of the diarrhea was also observed with the alpha 2-receptor agonist clonidine. These observations indicate that these classes of drugs should be evaluated in a controlled trial in patients with carcinoid-associated diarrhea.

Topics: Antiemetics; Clonidine; Diarrhea; Humans; Indoles; Male; Malignant Carcinoid Syndrome; Middle Aged; Ondansetron; Tropisetron

Serotonin antagonists have been proven antisecretory in cholera toxin (CT)-induced hypersecretion in the small intestine of rodents. The pig small intestine is a good model for the human small intestine with regard to physiologic and pharmacologic processes.. The antisecretory effect of intraluminally administered methysergide, renzapride, ketanserin, granisetron, and tropisetron on CT-induced hypersecretion was tested in isolated pig jejunal loops in vivo.. Methysergide, ketanserin, and granisetron reduced the hypersecretory effect of CT maximally by 25%, 80%, and 50%, respectively. Tropisetron enhanced whereas renzapride did not alter the CT response. Combination of ketanserin and granisetron gave a maximal inhibitory effect of about 85%. Surprisingly, renzapride, granisetron, and tropisetron each induced hypersecretion. Taking into account the hypersecretory effect of the antagonists, they all reduced this CT-elicited hypersecretion.. Results suggest involvement of the 5-hydroxytryptamine-2 and 5-hydroxytryptamine-3 receptor subtypes as mediators in CT-induced hypersecretion in pig jejunum, and antidiarrheal therapeutic potentials of ketanserin and granisetron.

Topics: Animals; Animals, Newborn; Benzamides; Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Cholera Toxin; Diarrhea; Dose-Response Relationship, Drug; Drug Therapy, Combination; Granisetron; Indoles; Intestinal Secretions; Jejunum; Ketanserin; Methysergide; Serotonin Antagonists; Swine; Tropisetron

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

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

Therapy for diarrhoea associated with the carcinoid syndrome is often unsatisfactory. In an open study ICS 205-930 (Sandoz Limited), a novel 5HT3-antagonist, controlled diarrhoea in five of six patients studied. This drug may be a useful advance in the symptomatic treatment of the carcinoid syndrome.

Topics: Adult; Aged; Diarrhea; Female; Humans; Indoles; Injections, Intravenous; Male; Malignant Carcinoid Syndrome; Middle Aged; Serotonin Antagonists; Tropisetron

Topics: Adult; Diarrhea; Female; Fever; Humans; Indoles; Serotonin Antagonists; Tropisetron