盐酸恩丹西酮与胃复安治疗以顺铂或阿霉素联合化疗诱发恶心呕吐──311例Ⅱ期临床试验随机自身对照疗效比较

３１１例以顺铂和阿霉素联合方案化疗的恶性肿瘤患者，采用国产盐醚恩丹西酮与胃复安进行自身随机对照止吐研究。结果表明，恩丹西酮对顺铂联合方案引起的急性呕吐治疗，第１、２、３天有效率分别为９２．５％、８８．９％及８２．９％，明显优于胃复安的４２．２％、５６．３％及５９．３％（Ｐ＜０．０５）；恩丹西酮对阿霉素联合方案化疗引起的急性呕吐治疗，第１、２、３天有效率分别为９７．７％、９３．８％及９５．８％，而胃复安有效率为９２．０％、８４．１％及８１．３％。在副作用方面，恩丹西酮治疗组除便秘（４５例次．１１．７％）高于胃复安治疗组（且７例次，４．４％）外，无其它明显毒副反应；相反，胃复安治疗组中有７例（１．８％）发生锥体外系反应．而恩丹西酮治疗组中无一例出现。我们认为，恩丹西酮止吐疗效好，使用安全，尤其适合治疗顺铂类药物化疗所致的急性严重呕吐。     

恩丹西酮（齐鲁）预防顺铂所致呕吐的Ⅱ期临床研究

１６７例病人，随机对照观察恩丹西酮（齐鲁）的止吐作用。顺铂为３０ｍｇ／次×５天、５０ｍｇ／次×３天或５０ｍｇ／ｍ￣２×１～２天。化疗第１周期用恩丹西酮或用对照药－胃复安或枢复宁，第２周期交换。结果恩丹西酮对控制急性呕吐的有效率高达８６．６％，而胃复安仅为３５．４％。第１天平均呕吐次数两药分别为１．１次／日和５．７次／日（Ｐ＜０．００１）。恩丹西酮对迟发性呕吐也较胃复安为好。恩丹西酮与枢复宁比较，止吐效果相似。恩丹西酮对顺铂所致呕吐效果甚佳，副作用小，是肿瘤化疗的良好止吐药。     

恩丹西酮（齐鲁）预防非顺铂化疗所致呕吐的Ⅱ期临床研究

本组采用随机对照方法观察恩丹西酮（齐鲁）的止吐作用。凡第１次接受含环磷酰胺、阿霉素的联合方案后出现呕吐的患者入组，第２次化疗时随机用恩丹西酮或用对照药（胃复安或枢复宁），第３次化疗时交换。共１５５例患者入组。结果显示，恩丹西酮第１天的止吐有效率为８７．７％，胃复安为６１．６％；平均呕吐次数分别为０．８次／日和２．７次／日（Ｐ＜０．０１）。恩丹西酮与枢复宁比较止吐效果相似。恩丹西酮对非顺铂化疗引起的呕吐具有很好的止吐效果，副作用小。     

恩丹西酮（齐鲁）预防顺铂所致呕吐的II期临床研究

１６７例病人，随机对照观察恩丹西酮（齐鲁）的止吐作用。顺铂为３０ｍｇ／次×５天、５０ｍｇ／次×３天或５０ｍｇ／ｍ＾２×１￣２天。化疗第１周期用恩丹西酮或用对照药－胃复安或枢复宁，第２周期交换。结果恩丹西酮对控制急性呕吐的有效率高达８６．６％，而胃复安仅为３５．４％。第１天平均呕吐次数两药分别为１．１次／日和５．７次／日（Ｐ〈０．００１）。恩丹西酮对迟发性呕吐也较胃复安为好。恩丹西酮与枢复宁比较，止     

恩丹西酮（齐鲁）预防非顺铂化疗所致呕吐的II期临床研究

本组采用随机对照方法观察恩丹西酮（齐鲁）的止吐作用。凡第１次接受含环磷酰胺、阿霉素的联合方案后出现呕吐的患者入组，第２次化疗时随用恩丹酮酮或用对照药（胃复安或枢复宁），第３次化疗时交换。共１５５例患者入组。结果显示，恩丹西酮第１天的止吐有效率为８７．７％，胃复安为６１．６％；平均呕吐次数分别为０．８次／日和２．７次／日（Ｐ〈０．０１）。恩丹西酮与枢复宁比较止吐效果相似。恩丹西酮对非顺铂化疗引起的呕     

国产恩丹西酮预防化疗引起恶心呕吐80例临床观察

采用随机对照法观察了恩丹西酮对８０例顺铂及非顺铂类化疗药的止吐作用，化疗第１周期用恩丹西酮或胃复安，第２周期交换。结果显示，恩丹西酮对控制急性呕吐的有效率为９１．３％，而胃复安仅为５８．８％（Ｐ〈０．０１），其对非顺铂类的止吐作用，前２天优于顺铂（Ｐ〈０．０５），它对迟发性呕吐的疗效也优于胃复安，本研究认为，恩丹西酮控制顺铂及非顺铂类化疗引起的恶心呕吐均有良好的疗效，副作用少。     

大剂量顺铂所致恶心、呕吐的联合治疗

目的 观察联合止吐方案（恩丹西酮＋地塞米松＋安定＋胃复安＋苯海拉明）对大剂量顺铂化疗所致恶心,呕吐的治疗效果。方法 50例接受大剂量顺铂化疗的恶性肿瘤患者,采用自身随机对照的方法,分别在第1周期采用联合止吐方案,第2周期采用常规止吐方案（胃复安＋苯海拉明）,或者在第1周期采用常规止吐方案,第2周期采用联合止吐方案,以观察联合止吐方案的止吐效果。结果 联合止吐方案1、2、3天的止吐有效率分别为90％、86％、92％,明显高于常规止吐方案（P＜0．01）。结论 联合止吐方案止吐效果好,减少了恩丹西酮的用量、节省了医疗费用,便于在临床推广使用。     

不同止吐方案预防化疗所致呕吐的对比研究

目的 从几组化疗止吐剂中筛选出经济有效，便于基层医院应用的抗癌止吐方案。方法 胃复安为对照组，恩丹西酮或欧必亭综合防治用药为观察组，进行自身前后对照，以止吐效果为主要指标的多侧面观察比较。结果 止恶心有效率，急性期和延迟期呕吐防治有效率分别为：胃复安组38．88％，36．41％，33．33％，恩丹西酮或欧必亭组78．34％，86．67％，76．67％；综合防治组74．50％，83．33％，91．18％。未见严重副反应。结论 以胃复安，苯海拉明，地塞米松，安定联合按需用药是基层医院较理想的抗癌化疗止吐方案。     

盐酸恩丹西酮预防化疗所致呕吐Ⅱ期临床研究

观察国产５－ＨＴ３阻滞剂－盐酸恩丹西酮预防化疗所致呕吐的临床疗效。方法：采用随机自身交替对照方法分为两组观察，接受顺铂联合化疗组及非顺铂联合化疗组各２５例。盐酸恩丹西酮８ｍｇ，化疗前１５分钟静注，恩丹西酮８ｍｇ，化疗后８小时口吸口服。对照组：胃复安２０ｍｇ，化疗前１５分钟肌注，胃复安８ｍｇ化疗后８小时口服。     

托烷司琼联用预防化疗呕吐临床研究

目的 观察托烷司琼联用地塞米松及胃复安防止化疗所致呕吐的临床疗效和毒性作用。同时选恩丹西酮联用等量地塞米松、胃复安作对照组进行分析。方法 45例接受顺铂或环磷酰胺加阿霉素联合化疗者随机分为两组,于每组化疗两个周期中交叉用药,自身对照。观察第1～5天患者恶心、呕吐控制的有效率(CR PR)并作出比较。结果 含顺铂化疗组托烷司琼联用,急性期止吐有效率93.8％,CR87.5％。恩丹西酮联用有效率96.7％,CR81.3％。迟发期有效率84.4％～90.6％,两药相似。结论 托烷司琼与恩丹西酮疗效相同,防止化疗呕吐效果显著,无严重毒性作用。联用地塞米松和胃复安可以提高两药疗效,尤其对迟发期呕吐取得较为满意的作用。     

枢复宁防止由非顺铂化疗所致呕吐的疗效观察

本文报道用枢复宁十地塞米松与灭吐灵十地塞米松随机对照,控制非顺铂化疗诱发的呕吐。58例病人经随机分组后,28例用枢复宁加地塞米松,30例按本院常用剂量灭吐灵加地塞米松治疗。枢复宁十地塞米松对急性恶心和呕吐的完全控制率均显著高于灭吐灵十地塞米松(分别为87％比72％,P<0.05,94％比67％,P<0.001)。对延缓性呕吐的完全控制。枢复宁十地塞米松也高于灭吐灵十地塞米松,分别为85％—94％比58％—82％(P<0.05)。枢复宁十地塞米松副作用轻,主要有头痛(13％)和便秘(9％),不引起锥体外系反应。因此,枢复宁十地塞米松是一个较为有效的联合止吐方案。     

Ondansetron versus metoclopramide in the prevention of chemotherapy-induced nausea and vomiting - a metaanalysis

Nausea and vomiting remain important clinical problems occuring in 25 to 50% of patients receiving chemotherapy for cancer. Clinical trials comparing a new antiemetic drug, ondansetron, to metoclopramide have suggested improved control of nausea and vomiting but studies disagree on the magnitude of the treatment effect and its statistical significance. We combined evidence from randomized controlled trials in a meta-analysis of the efficacy and safety of ondansetron compared to metoclopramide in the prevention of acute (less-than-or-equal-to 24 hours) nausea and emesis associated with chemotherapy. Literature search identified six randomised controlled trials of ondansetron versus metoclopramide in an adult population. Study outcomes were the observed incidence of emesis (vomiting or retching) and patient-reponed grades of nausea after chemotherapy. For meta-analysis of each outcome we defined therapeutic success as complete protection (ie. zero episodes during 24 hours following chemotherapy). The relative odds of success (ondansetron/metoclopramide) was calculated for each trial and all trials combined. Results were expressed as a relative risk (RR) for zero emesis or nausea at 24 hours. The six trials reported on 705 patients (median age range 53-59 years; 57% female). Relative odds for complete control of emesis was greater than one in all trials but was nonsignificant (p>0.05) in two trials, including the largest trial. When trials were combined, summary odds ratios for control of emesis and nausea were greater than one (p<0.05). RR of zero emesis with ondansetron was 1.72 (95% CI 1.45 to 1.97) and was similar for nausea (RR= 1.78, 95% CI 1.39 to 2.13). In trials using high-dose cisplatin chemotherapy, higher rates of extrapyramidal affects and diarrhea were associated with metoclopramide (p<0.05) while headache was frequently associated with ondansetron (p<0.05). Combined clinical trial evidence supports the conclusion. that, relative to metoclopramide, ondansetron places patients at a much lower risk of nausea and emesis following chemotherapy with moderately or highly emetogenic regimens.     

Ondansetron Versus Metoclopramide as Antiemetic Treatment During Cisplatin-based Chemotherapy: A prospective study with special regard to electrolyte imbalance

Cancer patients selected for cisplatin-based chemotherapy were randomly divided into two groups (42 patients in each) which received either metoclopramide or ondansetron as antiemetics. Metoclopramide was given i.v. with 5 doses of 2 mg/kg starting 30 min before the cisplatin infusion and continued with one dose every 3 h. Ondansetron was given with a first injection of 8 mg i.v. 30 min before the cisplatin infusion; the patients were given 8 mg orally 5 and 10 h after the cisplatin infusion followed by 8 mg × 3 during the next two days. In the present study ondansetron was superior to metoclopramide concerning antiemetic efficacy and gave also less side-effects as diarrhea, dizziness, extrapyramidal symptoms and electrolyte imbalance (sodium, potassium, magnesum, phosphorous) during the first 24 h following the cisplatin infusion.     

Ondansetron: a specific 5-HT3 serotonin receptor inhibitor, a new antiemetic in oncology

Serotonin (5-Hydroxytryptamine) seems to play a dominant role in triggering vomiting induced by cytotoxic agents through the stimulation of 5-HT3 receptors. They have been observed in the GI tract as well as in the brain (area postrema). Ondansetron is a specific antagonist of 5-HT3 serotonin receptors. Its anti-emetic activity is very powerful in the ferret. The availability of an injectable or oral form of this product allows the overall treatment of acute and delayed emesis and its administration is in accordance with different schedules: single IV injection or a continuous 24 hour infusion or repeated IV injection followed by oral treatment. The pharmacokinetics of the drug are as follows: absorption begins about 30 minutes after the administration per os, its biodisponibility is about 60%, its clearance: 20 ml/minute and its elimination half life about 3 hours. Different double blind studies, carried out in parallel groups or in cross over, demonstrated the superiority of ondansetron over metoclopramide in the control of nausea and vomiting, whether or not the chemotherapy contained cisplatin; a more recent study shows also that ondansetron was superior to alizapride and methylprednisolone in combination. Side effects of ondansetron do not include extrapyramidal symptoms but only headaches and constipation. The use of ondansetron improves the well-being of patients receiving chemotherapy and increases protocol compliance.     

Optimum anti-emetic therapy for cisplatin induced emesis over repeat courses: Ondansetron plus dexamethasone compared with metoclopramide, dexamethasone plus lorazepam

BACKGROUND:: This study was undertaken to compare the efficacy and tolerabilityof ondansetron plus dexamethasone (O+D) with metoclopramideplus dexamethasone plus lorazepam (M+D+L) over three consecutivecourses of cisplatin chemotherapy. PATIENTS AND METHODS:: This was an international, multicentre, double-blind, double-dummy,parallel group study. O+D patients were randomised to receiveondansetron 8 mg intravenously (i.v.) plus dexamethasone 20mg i.v. prior to cisplatin (50–100 mg/m) chemotherapy.On the following 4 days they were treated with ondansetron 8mg bd orally and dexamethasone 4mg bd orally. M+D+L patientswere randomised to receive metoclopramide 3 mg/kg i.v., dexamethasone20 mg i.v. and lorazepam 1.5 mg/m² i.v. (max 3 mg) prior tocisplatin chemotherapy and a further dose of metoclopramide3 mg/kg i.v. approximately 2 hours following the first doseof metoclopramide. Treatment for the following 4 days was metoclopramide40 mg tds and dexamethasone 4 mg bd orally. Two hundred andthirty-seven patients were recruited into the study (117 patientsreceived O+D and 120 received M+D+L). RESULTS:: On the first course of chemotherapy, O+D was significantly superiorto the M+D+L regimen for complete control of emesis (days 1–5,54% versus 37%, respectively, P = 0.014). This was maintainedover the three treatment cycles; 38% of O+D and 20% of M+D+Lpatients remained free of emesis (P = 0.003). Maintenance ofcontrol of nausea grade as none or mild on days 1–5 overthe three courses was significantly better in the O+D group(48%) than in the M+D+L (26%, P = 0.003). The most commonly occurring adverse events in the O+D groupwere constipation (25%) and headache (19%). In the M+D+L groupdrowsiness (38% of patients), malaise/fatigue (16% of patients),constipation (13% of patients), anxiety (11% of patients) anddizziness (10% of patients) were the most commonly reportedadverse events. Extrapyramidal symptoms were reported by 20%of patients in the M+D+L group. Despite the inclusion of lorazepam,14% of patients in the M+D+L group were withdrawn from the studydue to extrapyramidal symptoms, which in the opinion of theinvestigators, were probably or almost certainly related tostudy medication. CONCLUSIONS:: This study shows that O+D is significantly more effective andbetter tolerated than M+D+L for the control of emesis and nauseaover a series of three courses of cisplatin chemotherapy. cisplatin, emesis, nausea, ondansetron, repeated treatments     

Comparative trial of oral granisetron and intravenous ondansetron in patients receiving chemotherapy for breast cancer. Study Group of Granisetron

This multicentric randomized trial compared two strategies in the prevention of acute and delayed nausea and vomiting induced by moderately emetogenic chemotherapy in patients with breast cancer. The antiemetic efficacy and side effects of oral granisetron, followed by metoclopramide, were compared to those of intravenous (IV) ondansetron followed by oral ondansetron. 198 chemonaive patients with breast cancer, treated with a moderately emetogenic chemotherapy, were randomly assigned to receive either oral granisetron 1 mg twice a day on day 1, followed by metoclopramide, 60 mg on day 2 and 3, or ondansetron, 8 mg IV on day 1, followed by ondansetron 8 mg tablet twice a day on day 2 and 3. Both treatments have shown similar control of acute emesis: complete response was achieved in 71% of granisetron group and 66% of ondansetron, and total response in respectively 49% and 53%. However, granisetron plus metoclopramide showed a trend towards better efficacy than oral ondansetron in the prevention of delayed emesis. Furthermore, during the overall study period (day 1 to 5), the percentage of complete responses in the group receiving oral granisetron followed by oral metoclopramide was significantly higher than in the group receiving ondansetron (53% versus 37%; p = 0.022). In conclusion, oral granisetron has shown similar efficacy as IV ondansetron in the prevention of acute emesis induced by moderately emetogenic chemotherapy. Oral granisetron followed by metoclopramide seems more efficient than IV plus oral ondansetron in the prevention of delayed emesis.     

Phase III double-blind comparison of intravenous ondansetron and metoclopramide as antiemetic therapy for patients receiving multiple-day cisplatin-based chemotherapy.

BACKGROUND. Ondansetron hydrochloride is a selective serotonin subtype 3 (5HT3) receptor antagonist that has been shown to be an effective antiemetic in patients receiving cisplatin chemotherapy. METHODS. This double-blind study compared the safety and efficacy of intravenous ondansetron with metoclopramide in patients receiving a 4- or 5-day regimen of cisplatin (20-40 mg/m2/day) combination chemotherapy. Forty-five patients were enrolled, and efficacy of the drug therapy could be studied for all 45. Patients were randomly assigned (1:1) to receive three daily intravenous doses of either 0.15 mg/kg ondansetron or 1 mg/kg metoclopramide. All patients were monitored daily for the number of emetic episodes (vomiting or retching), severity of nausea, adverse events, and laboratory safety parameters. RESULTS. Seven (30%) patients who received ondansetron had no emetic episodes throughout the entire study period compared with two (9%) who received metoclopramide (P = 0.077). The greatest difference in antiemetic efficacy was seen on day 1, when 18 (78%) patients who received ondansetron had no emetic episodes compared with 3 (14%) patients who received metoclopramide (P < 0.001). Significantly fewer antiemetic treatment failures (more than five emetic episodes or withdrawal from the study) occurred with patients given ondansetron (9%) than with those given metoclopramide (50%) during the entire study period (P = 0.002). The most commonly reported adverse event associated with ondansetron therapy was headache (controlled with acetaminophen), whereas diarrhea and restlessness were the most commonly reported adverse events associated with metoclopramide therapy. Extrapyramidal symptoms were judged to have occurred in 13 patients who received metoclopramide and 1 patient who received ondansetron. However, the patient who received ondansetron subsequently was judged to have had an anxiety attack. In patients with low or normal baseline transaminase values, a greater percentage who received ondansetron had transient increases as great as twice the upper limit of normal in aspartate transaminase (5% versus 0%) and alanine transaminase (17% versus 6%) than those who received metoclopramide. CONCLUSIONS. Ondansetron is superior to metoclopramide as antiemetic therapy for multiple-day cisplatin-based chemotherapy.     

Ondansetron compared with metoclopramide in the control of emesis and quality of life during repeated chemotherapy for breast cancer.

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 greater than or equal to 500 mg/m2). Patients received an intravenous dose of 16 mg dexamethasone 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 less than 0.001). Over the 5-day treatment period, the corresponding figures were 81 and 48% (p less than 0.001). The results for nausea also revealed highly statistically significant treatment differences (p less than 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 less than 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 less than 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 less than 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.(ABSTRACT TRUNCATED AT 400 WORDS)     

A comparison of ondansetron with metoclopramide in the prophylaxis of chemotherapy-induced nausea and vomiting: A randomized,double-blind study

The efficacy of ondansetron was compared with metoclopramide in the prophylaxis of nausea and vomiting induced by cyclophosphamide ≥ 500 mg/m² in combination with doxorubicin ≥ 40 mg/m² or epirubicin ≥ 40 mg/m². Complete anti-emetic protection in the 24 h following chemotherapy was achieved in 26 of 40 (65%) patients treated with ondansetron compared with 17 of 42 (41%) patients treated with metoclopramide. Severe nausea was present in 3% of patients in the ondansetron group and 31% in the metoclopramide group. A worst day analysis of control of emesis and nausea on days 2 and 3 following chemotherapy also demonstrated ondansetron to be more effective than metoclopramide. Both treatments were well tolerated. Ondansetron is more effective as an anti-emetic than metoclopramide in this type of cytostatic therapy.