ISSN:0030-2414    

DOI:10.1159/000227168

出版商:S. Karger AG    

年代:1993

数据来源: Karger

ISSN:0030-2414    

DOI:10.1159/000227169

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The treatment of cancer patients has improved over the last few years for a variety of reasons. These include improvements in diagnosis, more potent chemotherapeutic drugs and the introduction of new ways of containing or eliminating cancers by the use of multi-modality treatment regimens often facilitated by the use of chemoprotective agents. Cancer patients have also benefited from an increased awareness of their needs, with health care professionals paying attention to toxicities of treatment and optimising treatment schedules to combine the best possible medical outcome with patient comfort and acceptability of treatment. Thus not all the advances seen in the management of cancer patients have relied upon the introduction of novel anti-tumour agents; important advances have been made by the optimal use of existing drugs, the revision of treatment schedules and better control of the side effects of treatment. One of the more distressing side effects of cancer chemotherapy, having a profound effect on its acceptability to patients, is nausea and vomiting. The introduction over the last 3 years, of ondansetron, the first generally available 5-HT3 receptor antagonist, has had beneficial effects on the management of patients. Through improvements in anti-emetic control ondansetron has provided a better quality of life and is now beginning to impact on the design and administration of conventional chemotherapy treatment schedules. This paper reviews the changes that have been seen with the use of ondansetron and makes several suggestions about areas where clinicians might find a beneficial role for 5-HT3 receptor antagonists.

ISSN:0030-2414    

DOI:10.1159/000227170

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

This paper describes a multicentre, double-blind, parallel group study which compared ondansetron (0.15 mg/kg i.v. X 3) plus dexamethasone (20 mg i.v.) with metoclopramide (3 mg/kg i.v. X 2) plus dexamethasone (20 mg i.v.) and diphenhydramine (50 mg i.v.) for the prevention of cisplatin-induced emesis and nausea. Two hundred and eighty-nine consecutive patients receiving chemotherapy containing cisplatin at doses > 50 mg/m2 entered the study and 267 patients were evaluable for efficacy. The ondansetron regimen was significantly superior compared with the metoclopramide regimen in the control of acute emesis and nausea. Ondansetron plus dexamethasone provided complete protection against retching and vomiting in 79% of patients compared with 59% of patients given the metoclopramide combination (p < 0.002). Similarly ondansetron plus dexamethasone completely prevented nausea in 77% of patients, whereas the metoclopramide combination protected 66% of patients (p < 0.051). Success (no nausea and no emesis) was afforded to 69% of those patients given ondansetron plus dexamethasone as opposed to 50% of patients given the metoclopramide combination (p < 0.003). From day 2–4 all patients received the same anti-emetic regimen of oral metoclopramide and intramuscular dexamethasone. Significantly fewer patients who had received the ondansetron regimen on day 1 vomited on days 2 and 3 compared with those who had received the triple drug combination (84–86 and 68–71%, respectively, p < 0.006). Nausea was also better controlled in this group on day 2. On subsequent cisplatin cycles, the incidence of acute vomiting rose to 53% in those patients given the metoclopramide regimen, but remained low (26%) in the group treated with ondansetron plus dexamethasone. Patients receiving the metoclopramide regimen had significantly more sedation than patients receiving ondansetron plus dexamethasone (12 vs. 2%; p < 0.005). Extrapyramidal reactions were only observed in metoclopramide-treated patients (3%). The results of this study suggest that ondansetron plus dexamethasone is a more effective and better tolerated anti-emetic regimen compared with metoclopramide plus dexamethasone and diphenhydramine for the prevention of acute cisplatin-induced e

ISSN:0030-2414    

DOI:10.1159/000227171

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

This randomised, double-blind, parallel-group study was carried out to compare the efficacy and safety profile of ondansetron plus dexamethasone and metoclopramide plus dexamethasone in patients receiving fractionated cisplatin (20-25 mg/m2/day) chemotherapy for the treatment of testicular cancer. An interim analysis of 95 patients showed that the ondansetron regimen was significantly superior compared to the metoclopramide regimen (p < 0.001). According to the study protocol the study was terminated at this stage. At the time the decision to stop the study was taken, a total of 113 patients had been enrolled and were evaluable on an ‘intention to treat’ basis. Fifty-six of these had received ondansetron (32 mg i.v. single dose/day) plus dexamethasone (20 mg i.v. single dose/day) and 57 were given metoclopramide (2 mg/kg or 1 mg/kg i.v. twice a day) plus dexamethasone (20 mg i.v. single dose/day). The ondansetron regimen was significantly superior in the control of emesis and nausea. Seventy-one percent of patients experienced 2 or fewer emetic episodes over the entire 5-day study period compared with 26% of patients given metoclopramide (p < 0.001). Seventy-nine percent of patients in the ondansetron group experienced ‘none’ or only ‘mild’ nausea compared with 39% of patients in the metoclopramide group (p < 0.001). The dose of metoclopramide had to be reduced during the study from 2 mg/kg i.v. twice daily to 1 mg/kg i.v. twice daily because 4 of the first 8 patients randomised to this treatment experienced extrapyramidal reactions. Ondansetron was well tolerated and it did not induce any extrapyramidal reactions. The results of this study show that ondansetron plus dexamethasone represents a very effective treatment option for patients receiving fractionated cisplatin chemotherapy for testic

ISSN:0030-2414    

DOI:10.1159/000227172

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

This paper reviews experience with ondansetron in radiotherapy-induced emesis. The efficacy of ondansetron is assessed following a number of different radiotherapy regimens: single-dose radiotherapy, fractionated radiotherapy, total body irradiation (TBI) and hemi-body irradiation. In single-dose radiation-induced emesis, ondansetron (8 mg orally 3 times daily) provided superior anti-emetic control compared with metoclopramide (10 mg orally 3 times daily): 92 and 46% of patients, respectively, experienced complete control of emesis (0 emetic episodes) in the first 24 h following treatment (p < 0.001). Similarly, ondansetron (8 mg orally 3 times daily) was significantly (p < 0.001) more effective than prochlorperazine (10 mg orally 3 times daily) with 59 and 35% of patients, respectively, achieving complete control of emesis on the ‘worst day’ of a fractionated radiotherapy regimen (up to 20 fractions). Two studies evaluating the efficacy of ondansetron in TBI-induced emesis have demonstrated that ondansetron is effective in paediatric and adult patients receiving chemotherapy and TBI prior to bone marrow transplantation. In these studies, 57-81 % of patients experienced 2 or fewer emetic episodes during TBI. For hemi-body irradiation, ondansetron (8 mg) and dexamethasone (8 mg) given orally produced complete control of emesis in 12 out of 14 patients. The effectiveness of this regimen now enables patients receiving hemi-body irradiation to be treated as outpatients in many cases. Anecdotal data also shows that ondansetron is effective when given as intervention treatment in patients with established emesis. In none of the studies were there any serious adverse events following ondansetron treatment. It can therefore be concluded that ondansetron is an effective and well tolerated antiemetic for the prophylaxis and treatment of radiation-induced emesis and nausea. The use of effective anti-emetic treatments may have resource implications such as reducing bed occupancy and enabling the use of fewer, larger fractions of radiother

ISSN:0030-2414    

DOI:10.1159/000227173

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Cyclophosphamide-based chemotherapy is often given to patients for the treatment of breast cancer. This chemotherapy can induce severe nausea and vomiting in these patients, which can adversely affect their quality of life, especially as these regimens are often given on an outpatient basis over several courses. This paper reviews 5 randomised, double-blind, multicentre comparative studies which have been carried out in breast cancer patients to evaluate the efficacy and safety profile of the potent and highly selective 5-HT3 receptor antagonist, ondansetron. These studies have shown that ondansetron is superior to placebo in the control of emesis induced by a 14-day CMF schedule and that it is superior to conventional anti-emetics (metoclopramide and alizapride) in the control of acute and delayed emesis induced by regimens containing high-dose cyclophosphamide. Ondansetron was well tolerated in these studies and did not induce any extrapyramidal reactions. The efficacy and tolerability of ondansetron was reflected in a better quality of life for patients given this anti-emetic which was formally assessed in 2 of the studies using the Rotterdam Symptom Checklist or the Functional Living Index – Emesis. In conclusion, ondansetron is an effective and well-tolerated anti-emetic for patients receiving cyclophosphamide-based chemotherapy for the treatment of breast cancer. Ondansetron provides significant benefits for patients’ quality of life compared with conventional anti-emetics particularly as these patients are often treated on an outpatient basis and can be treated with oral ondansetron at h

ISSN:0030-2414    

DOI:10.1159/000227174

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

A cost-effectiveness analysis is one form of full economic evaluation where drug acquisition costs and the costs that are incurred as a result of using a particular treatment are assessed together with clinical efficacy. This paper reviews two such studies. One of the studies was a prospective randomised cost-effectiveness study which compared ondansetron (8 mg i.v. 0, 4 and 8 h following chemotherapy) with metoclopramide (3 mg/kg i.v. followed by an infusion of 0.5 mg/kg/h for 8 h) over the first 24 h following chemotherapy in hospitalised patients receiving highly emetogenic chemotherapy. This study showed that the cost per successfully treated patient (defined in this study as having < 1 emetic episode and no adverse events) for these 2 treatments were approximately equal: ondansetron E95 and metoclopramide E92. The second study was an economic evaluation based on data collected over a 5-day period following cyclophosphamide-based chemotherapy given on an outpatient basis for the treatment of breast cancer. Patients received an intravenous dose of 16 mg dexamethasone with either 8 mg ondansetron or 60 mg metoclopramide intravenously before chemotherapy followed by oral dosing with 8 mg ondansetron or 20 mg metoclopramide 3 times daily for 5 days. The costs per successfully treated patient (defined in this study as no vomiting or retching episodes and no anti-emetic-related adverse events during the 5-day period) were comparable: ondansetron E184 and metoclopramide E160. A recent study has established that ondansetron (8 mg) given orally twice daily is as effective as the same dose given 3 times a day. A sensitivity analysis using the cost of an ondansetron twice daily regimen showed that ondansetron is more cost-effective than metoclopramide (E133 vs. E 160). These cost effectiveness studies have shown that ondansetron is at least as cost-effective as metoclopramide and simplified ondansetron dosing schedules render ondansetron more cost-effective. These full economic evaluations illustrate that drug acquisition costs can be a misleading guide to the economic impact of antiemetics.

ISSN:0030-2414    

DOI:10.1159/000227175

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Ondansetron was first synthesised in 1983 and it is estimated that over 4 million patient treatments have been given with ondansetron in clinical practice. Clinical trials in over 15,000 patients have demonstrated that ondansetron is effective and well tolerated in a range of clinical settings, including adults and children and over repeated courses of treatment. Ondansetron is convenient to administer, being effective as a single intravenous dose for the control of acute emesis and as oral therapy on a twice-daily schedule. Recent studies have also shown it to be a cost-effective anti-emetic when the costs of treatment failure of traditional anti-emetics are taken into account. Studies have also demonstrated an improved quality of life with ondansetron compared to treatment with metoclopramide. Ondansetron has also been found to be effective in the prevention or treatment of postoperative nausea and vomiting and other studies are underway to investigate its potential use in other clinical settings. Furthermore, appropriately designed trials are ongoing to evaluate the place of ondansetron in the control of cisplatin-induced delayed emesis. In conclusion, ondansetron has been shown to be a major advance in the control of nausea and vomiting associated with chemotherapy and radiotherapy.

ISSN:0030-2414    

DOI:10.1159/000227176

出版商:S. Karger AG    

年代:1993

数据来源: Karger

ISSN:0030-2414    

DOI:10.1159/000227177

出版商:S. Karger AG    

年代:1993

数据来源: Karger