ISSN:0030-2414    

DOI:10.1159/000227052

出版商:S. Karger AG    

年代:1992

数据来源: Karger

ISSN:0030-2414    

DOI:10.1159/000227053

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Ondansetron, a potent and highly selective 5-HT3 receptor antagonist, prevents emesis following chemotherapy by antagonising the action of 5-hydroxytryptamine (5-HT) at 5-HT3 receptors on vagal afferent neurones that innervate the gastrointestinal tract and 5-HT3 receptors in the central vomiting system. Evidence suggests that chemotherapy induces the release of 5-HT from enterochromaffin cells in the small intestine. This stimulates vagal afferent nerves via 5-HT3 receptors. Information is then relayed, via the vagus nerve, to the central vomiting system. 5-HT3 receptors are also found in the hind-brain vomiting system including the area postrema (the site of the chemore-ceptor trigger zone for emesis). Therefore, following chemotherapy, 5-HT activates 5-HT3 receptors at 2 sites to induce emesis. Clinical data showing that a single dose of ondansetron prevents acute emesis suggest that it is important to block the initiation of the emetic reflex. This may prevent the recruitment of central mechanisms involving 5-HT3 receptors.

ISSN:0030-2414    

DOI:10.1159/000227054

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

The most promising anti-emetic drugs are identified during preclinical testing. Phase I and II clinical studies are used to optimize doses and schedules for the various routes of administration. Most methodological issues arise in relation to phase III studies. A prospective, randomised, double-blind, parallel-subjects design is recommended. Stratification helps balance the factors influencing emesis between the 2 arms of a randomised study. The most important of these are the strength of the emetic stimulus, prior exposure to chemotherapy, age, sex and a history of chronic alcohol consumption. The evaluation of efficacy of an anti-emetic should include its efficacy in controlling acute post-chemotherapy nausea and vomiting as well as anticipatory and delayed emesis. The side effects of an anti-emetic must also be considered since they may negate any anti-emetic advantage. Patients and observers have reported successfully evaluating these parameters using both categorical and linear-analogue scales.

ISSN:0030-2414    

DOI:10.1159/000227055

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

This paper reviews data from 3 randomised, double-blind, parallel-group studies carried out in patients receiving high-dose cisplatin chemotherapy (50-120 mg/m2). These comparative trials show that a single intravenous dose of ondansetron (8-32 mg) is as effective as the continuous infusion and intermittent dose regimens used in previous clinical trials (8 mg i.v. followed by a 1 mg/h infusion for 24 h and 0.15 mg/kg i.v. X 3). One of the studies, carried out in Europe, demonstrated that a single 8 mg i.v. dose was as effective as 32 mg given either as an 8 mg loading dose followed by an infusion or as a single intravenous dose of 32 mg before chemotherapy. A similar study conducted in the United States showed that a 32 mg i.v. single dose was significantly more effective than both the 8 mg i.v. dose and the intermittent dose schedule. This study used a prospective stratification based on the dose of cisplatin (50-70 mg/m2 and ≥ 100 mg/m2). In both strata the 32 mg dose was superior. These results emphasise the importance of selecting the dose of ondansetron (8-32 mg) based on factors that predispose patients to emesis, e.g., female gender, patients with a history of chemotherapy or motion sickness and the dose of cisplatin. The ondansetron dosing regimen for patients receiving a highly-emetogenic chemotherapy (8-32 mg i.v. followed by 8 mg orally twice daily) is both simple and flexibl

ISSN:0030-2414    

DOI:10.1159/000227056

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Ondansetron was given as anti-emetic prophylaxis to 429 children receiving a variety of emetogenic cancer treatments for up to 8 days, in three, open, multicentre, European studies. Children aged between 6 months and 17 years with a variety of tumours and receiving chemotherapy or chemotherapy plus total body irradiation (TBI) were studied. Ondansetron was given intravenously, 5 mg/m2 or 8 mg, according to the surface area of the child, immediately before chemotherapy. Intravenous or oral treatment (2, 4 or 8 mg, according to surface area) was continued 3 times a day during chemotherapy or TBI, and for a further 2 days (non-cisplatin chemotherapy or TBI) or 5 days (cisplatin chemotherapy). The number of vomits and retches (each counting as an emetic episode) were recorded daily, as was an assessment of nausea, which was graded as none (not feeling sick at all), mild (feeling sick) or severe (feeling very sick). Responses were graded according to the number of emetic episodes during the worst 24-hour period. In addition, response was expressed in terms of emesis-free days as a proportion of all ondansetron treatment days. During chemotherapy, 66% of children experienced less than 3 emetic episodes on their ‘worst day’ and 88% had none or mild nausea. Sixty-eight percent of all ondansetron treatment days (2,131) were free of emesis. Of the patients who were poorly controlled with ‘customary’ anti-emetics, at least 81 % experienced better control with ondansetron. When analysed according to the most emetogenic agent given 36, 59 and 75 % of children reported less than 3 emetic episodes on their ‘worst day’ respectively, during cisplatin, ifosfamide and other less emetogenic chemotherapy. During conditioning for bone marrow transplantation with cyclophosphamide and TBI, 80 and 57% of patients, respectively, experienced less than 3 emetic episodes. The overall incidence of adverse events was low and headache (reported in 4% of patients) was the only event reported by more than 1 % of patients. These studies show that ondansetron is a safe, well tolerated and an effective anti-emetic in the treatment of children receiving a wide variety of chemothera

ISSN:0030-2414    

DOI:10.1159/000227057

出版商:S. Karger AG    

年代:1992

数据来源: Karger

ISSN:0030-2414    

DOI:10.1159/000227058

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

Information on patients’ quality of life (QOL) will give a more comprehensive evaluation of the treatment outcome than only measures of tumour response and survival. Psychosocial indicators have rarely been used in clinical trials. This may in part be explained by physicians’ lack of familiarity with these measures, methodological insufficiency and a basic philosophical reason, i.e., most doctors tend to focus on curative treatment and not on palliative treatment. A series of QOL questionnaires has been validated in the last decade for use in cancer clinical trials. Selection of the optimal method in the given trial is important. The trial ought to be designed so the proportion of missing data is low. QOL should be used as an end point in selective trials with an optimal study design and with a study coordinator who is willing to collect QOL d

ISSN:0030-2414    

DOI:10.1159/000227059

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

This was a multicentre, randomised, double-blind, parallel-group study which included female breast cancer patients, receiving their first of 6 scheduled courses of chemotherapy (cyclophosphamide ≥ 500 mg/m2). Patients received an intravenous dose of 16mg dexa-methasone with either 8 mg ondansetron or 60 mg metoclopramide before chemotherapy, followed by oral dosing with 8 mg ondansetron or 20 mg metoclopramide 3 times daily for 5 days. A total of 93 patients were treated with ondansetron and 94 patients with metoclopramide. On day 1 of their first course of treatment 91 and 60% of patients in the ondansetron and metoclopramide groups respectively were free of emesis (p < 0.001). Over the 5-day treatment period, the corresponding figures were 81 and 48% (p < 0.001). The results for nausea also revealed highly statistically significant treatment differences (p < 0.001) in favour of ondansetron for both day 1 and day 1-5 analyses of the first treatment course. Over the series of courses, 67% of patients receiving ondansetron completed all 6 courses with a maximum of 2 emetic episodes on their worst day, compared with 28% of patients receiving metoclopramide (p < 0.001). A similar analysis for nausea revealed that 49% of patients receiving ondansetron completed all 6 courses with ‘none’ or ‘mild’ nausea compared with 27% of patients receiving metoclopramide (p < 0.001). These differences were reflected in quality of life data (Rotterdam Symptom Checklist). After the first course of treatment, a statistically significant improvement (p = 0.002) in the psychological subscale scores was observed after ondansetron compared with metoclopramide. No differences were observed in the physical or functional activity subscales after the first course. However, the quality of life results over the series of courses revealed a more pronounced difference in favour of ondansetron in the psychological subscale scores (p < 0.001) as well as trends in favour of ondansetron in the physical (p = 0.096) and functional activity (p = 0.056) subscales. Extrapyramidal symptoms were reported in 19 % of patients in the metoclopramide group and resulted in 15 % of patients withdrawing from their randomised anti-emetic schedule, either during or between treatment courses. Other adverse events were generally minor in nature and did not necessitate withdrawal from treatment. In conclusion, this study shows that ondansetron is significantly superior to metoclopramide (each with a single pre-treatment dose of dexamethasone) in the control of emesis over 6 courses of chemotherapy for breast cancer. Importantly, patients given ondansetron had a superior quality of life compared with those given metoc

ISSN:0030-2414    

DOI:10.1159/000227060

出版商:S. Karger AG    

年代:1992

数据来源: Karger

摘要:

This randomised, single-blind, parallel-group study was carried out in 48 French pneumology centres to compare the anti-emetic efficacy of ondansetron and an alizapride plus methylprednisolone (ALI/MPS) combination in patients receiving high-dose cisplatin. A total of 220 patients were recruited of whom 209 were evaluable (100 on ondansetron and 109 on ALI/MPS). Thirty minutes before cisplatin, patients received either ondansetron (8 mg i.v.) or alizapride (4 mg/kg i.v.) combined with methylprednisolone (500 mg i.v.). The ondansetron and alizapride injections were repeated 4 and 8 h later. Thereafter, patients received oral ondansetron (8 mg) or alizapride (50 mg) 3 times daily for 5 days. Ondansetron was significantly superior to ALI/MPS in the control of acute emesis (p < 0.001); 88/100 (88%) of ondansetron, and 69/109 (63%) of ALI/MPS patients experienced less than 3 emetic episodes. Similarly, ondansetron was superior to ALI/MPS for the control of acute nausea (visual analogue scale at 24 h; 13 vs. 22 mm respectively, p = 0.0012). The superiority of ondansetron over days 2-6 was not as great as that over the first 24 h, although there was a trend in favour of ondansetron. More patients treated with ondansetron wished to take the same anti-emetic treatment again (83% for ondansetron vs. 56% for ALI/MPS, p < 0.001). Both treatments were well tolerated. This study shows that ondansetron is superior to a ben-zamide-corticosteroid combination in the control of acute cisplatin-induced emesis.

ISSN:0030-2414    

DOI:10.1159/000227061

出版商:S. Karger AG    

年代:1992

数据来源: Karger