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。     

枢复宁预防由顺铂化疗所致恶心呕吐的疗效观察

随机将４６例接受顺铂化疗的病人分成两组，分别采用枢复宁和灭吐灵预防顺铂引起的恶心呕吐，两组病人一般情况相近，所用化疗方案以顺铂为主，使用顺铂的剂量为３０ｍｇ－５０ｍｇ／次，每日一次，连用３天，枢复宁剂量１６ｍｇ／日，连服３天，灭吐灵剂量４０ｍｇ／天，边疆肌注３天。结果：枢复宁控制恶心的效果明显优于灭吐灵；对急性呕吐、枢复宁组有效率显著高于灭吐灵组；对控制延缓性呕吐的效果，两组无差异。     

枢复宁预防超大剂量单次全身放疗所致的恶心呕吐

１１６例急、慢性白血病患者因行骨髓移植接受单次超大剂量全身放疗，总剂量７００～７７０Ｇｙ，剂量率０．０５Ｇｙ／ｍｉｎ。７０例患者采用枢复宁＋地塞米松预防急性恶心呕吐反应，结果该组患者无恶心率４３％（３０／７０），轻度恶心率为４４％（３１／７０），呕吐完全控制率为６６％（４６／７０），每天１～２次呕吐发生率为１９％（１３／７０），总有效率为８４％（５９／７０）。而以灭吐灵＋地塞米松组无恶心率及轻度恶心率分别为２％（１／４６）和９％（４／４６），呕吐控制及部分控制率分别为２％（１／４６）和１７％（８／４６）。枢复宁抗全身放疗诱发急性恶心呕吐疗效明显优于灭吐灵。     

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     

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。     

三种5—羟色胺受体阻滞剂预防化疗药物所致消化道毒性的临床分析

目的探讨恩丹西酮、枢复宁、康泉预防化疗药物引起恶心呕吐的临床效果。方法采用随机对照法观察了对以顺铂为主化疗药物的止吐作用,选择病例分别为４０例、３２例及９５例。结果恩丹西酮、枢复宁、康泉对控制急性呕吐的有效率（ＣＲ＋ＰＲ）分别为：８５％、８４．４％、９６．８％,康泉与恩丹西酮、枢复宁比较均有统计学意义（Ｐ＜０．０５）,而恩丹西酮与枢复宁两者比较无统计学意义（Ｐ＞０．０５）。呕吐完全控制率（ＣＲ）三者分别为６５％、７５％及８１．１％,康泉与恩丹西酮比较有统计学意义（Ｐ＜０．０５）,而康泉与枢复宁及恩丹西酮与枢复宁比较均无统计学意义（Ｐ＞０．０５）。结论恩丹西酮与枢复宁对预防化疗药物引起的呕吐有效,而康泉的效果优于枢复宁及恩丹西酮。但是,康泉的价格昂贵,临床应用受到限制。     

康泉、灭吐灵、地塞米松在顺铂化疗中的应用

目的观察康泉、灭吐灵、地塞本松联合应用时18例卵巢癌40人次以顺铂为主的联合化疗所产生的恶心、呕吐作预防性治疗。方法康泉3mg溶于生理盐水40ml缓慢静注、灭吐灵10mg、地塞米松5mg肌注,半小时后开始化疗,化疗结束后半小时重复使用后两种药。24小时记录恶心、呕吐次数及程度、连续7天。结果O度：22人次,I度：15人次,止吐有效率92．5％（37／40）。急性呕吐有效率92．5％（37／40）,延迟期呕吐有效率95％（38／40）均高于文献报导的单独用康泉或灭吐灵止吐有效率。结论康泉、灭吐灵、地塞米松联合镇吐有效可行,且用量小,副作用少。     

康泉、灭吐灵、地塞米松在顺铂化疗中的应用

目的：观察康泉、灭吐灵、地塞米松联合应用时18例卵巢癌40人次以顺铂为主的联合化疗所产生的恶心、呕吐作预防性治疗。方法：康泉3mg溶于生理盐水40ml缓慢静注，灭吐灵10mg、地塞米松5mg肌注，半小时后开始化疗、化疗结束后半小时重复使用后两种药，24小时记录恶心呕吐次数及程度。连续7天，结果0度：22人次，Ⅰ度：15人次，止吐有效率92．5％（37／40）。急性呕吐有效率92．5％（37／40），延迟期呕吐有效率95％（38／40）均高于献报导的单独用康泉或灭吐灵止吐有效率，结论：康泉、灭吐灵、地塞米松联合镇吐有效可行，且用量小，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     

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。     

Chemotherapy-induced emesis: management of early and delayed emesis in milder emetogenic regimens

 The objective of the present study was to examine the problem of the control of nausea and vomiting induced by non-cisplatin containing cyclophosphamide-based chemotherapy regimens in breast cancer patients. This was randomized, double-blind, parallel-group and placebo-controlled study comparing the efficacy of three antiemetic therapeutic regimens (ondansetron for 3 days, ondasetron plus metoclopramide, and ondansetron given in a single dose) in breast cancer patients receiving cyclophosphamide-based chemotherapy regimens on an outpatient basis. Both the primary and the secondary efficacy were measured. The primary efficacy variable was the number of emetic episodies (considering early and delayed emesis). The secondary efficacy variable measured was the quality of life. Two-by-two tables using the chi-square test and relative-risk concept were elaborated for statistical analysis. There was no difference between high-dose ondansetron and ondansetron plus metoclopramide among patients given CMF (cyclophosphamide, methotrexate, 5-fluorouracil). The single-dose ondansetron regimen showed the worst results. In patients given an FEC regimen (cyclophosphamide, epirubicin, 5-fluorouracil) the antiemetic efficacy was best for the high-dose ondansetron regimen, followed by the ondansetron plus metoclopramide regimen, and was worst for single-dose ondansetron administration. Despite the use of different antiemetic schedules, nausea and emesis are significant problems in patients receiving cyclophosphamide-based chemotherapy. Their adequate control should be the aim of any antiemetic approach. Received: 23 September 1995/Accepted: 25 January 1996     

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.     

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.     

High efficacy of a single oral dose of ondansetron 8 mg versus a metoclopramide regimen in the prevention of acute emesis induced by fluorouracil, doxorubicin and cyclophosphamide (FAC) chemotherapy for breast cancer

The aim of our single-center, prospective, randomized, open study was to evaluate the antiemetic efficacy and tolerability of a regimen based on a single oral dose of ondansetron 8 mg in comparison with a metoclopramide-based regimen, for prevention of acute FAC (fluorouracil, doxorubicin and cyclophosphamide) chemotherapy-induced emesis. A total of 149 chemotherapy-naive, female outpatients, under 50 years of age and with no history of alcohol consumption, scheduled to receive their first cycle of FAC chemotherapy, were included. The patients received either oral ondansetron (8 mg) or metoclopramide (1.5 mg/kg, i.v.), both combined with dexamethasone (16 mg, i.v.) and alprazolam (0.5 mg t.i.d. orally). No antiemetic prophylaxis was given for delayed emesis. Complete control of acute vomiting was obtained in 69/74 (93%) of patients receiving ondansetron, and in 49/75 (65%) of those receiving metoclopramide (p=0.00003). Complete control of acute nausea was obtained in 58% of patients receiving ondansetron and in 36% of those receiving metoclopramide (p=0.007). Complete prevention of delayed vomiting/nausea was achieved in 73%/20% and 60%/16% of patients, respectively. Sedation was more frequent in the metoclopramide arm (p=0.04). As far as we know this is the first study that supports the efficacy of a regimen based on a single oral dose of ondansetron 8 mg in the prevention of acute FAC chemotherapy-induced emesis. The ondansetron regimen was highly effective in female patients and was superior to the metoclopramide based regimen.     

A single-blind comparison of intravenous ondansetron, a selective serotonin antagonist, with intravenous metoclopramide in the prevention of nausea and vomiting associated with high-dose cisplatin chemotherapy

Ondansetron (GR 38032F), a selective antagonist of serotonin subtype 3 receptors, is effective in the prevention of emesis associated with cisplatin as well as other chemotherapeutic agents. In this randomized, single-blind, multicenter, parallel group study, we compared the efficacy and safety of intravenous (IV) ondansetron with IV metoclopramide in the prevention of nausea and vomiting associated with high-dose (greater than or equal to 100 mg/m2) cisplatin chemotherapy. Three hundred seven patients receiving their first dose of cisplatin, either alone or in combination with other antineoplastic agents, were randomized to receive ondansetron 0.15 mg/kg IV every 4 hours for three doses or metoclopramide 2 mg/kg IV every 2 hours for three doses, then every 3 hours for three additional doses. The study prohibited the concurrent administration of other antiemetics or dexamethasone. Patients receiving ondansetron had a higher rate of complete protection from emesis (40% v 30%, P = .07), a higher complete plus major response rate (65% v 51%, P = .016), a lower rate of failure (21% v 36%, P = .007), and a lower median number of emetic episodes (one v two, P = .005) than did those receiving metoclopramide. The median time to the first emetic episode was longer on ondansetron (20.5 v 4.3 hours, P less than .001). Adverse events occurred in 48% of patients receiving ondansetron and 69% of those receiving metoclopramide (P less than .001). Akathisia and acute dystonic reactions occurred only on metoclopramide; headache (controlled with acetaminophen) was significantly more frequent with ondansetron. Ondansetron is more effective, produces fewer adverse events, and is easier to administer than metoclopramide for the prevention of emesis associated with high-dose cisplatin chemotherapy.     

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.     

恩丹西酮和胃复安预防顺铂化疗呕吐反应的疗效分析

采用自身对照方法，观察了１０６例恶性肿瘤病人以顺铂为主联合化疗，于第１，２周期分别使用胃复安，恩丹西酮。预防恶心呕吐反应，有效率分别为：４３．３９％，９２．４５％，二者差异显著。胃复安组８例发生椎体外系反应，恩丹西酮均未出现椎体外系症状。     

Antiemetic activity of the new 5-HT3 antagonist DAU 6215 in animal models of cancer chemotherapy and radiation

Summary The antiemetic activity of DAU 6215, a novel antagonist of 5-HT₃ receptors, was investigated in animal models of cytotoxic treatment-evoked emesis and compared with the antiemetic activity of ondansetron and metoclopramide. In dogs, vomiting was induced by i.v. cisplatin; in ferrets, the emetic response was elicited by i.v. doxorubicin or X-ray exposure. Pretreatment with 0.1–1 mg/kg DAU 6215 given i.v. or p.o. prevented the vomiting response to the different emetic agents. In the dog, the antiemetic potency of metoclopramide was 30 times lower than that of DAU 6215. Ondansetron was less potent than DAU 6215 against cisplatin and doxorubicin but was equally effective in the radiotherapy protocol. In this model, lengthening of the pretreatment time to 2 h did not affect the antiemetic efficacy of DAU 6215, whereas it decreased that of ondansetron. The results demonstrate that DAU 6215 is a highly effective and long-lasting inhibitor of cytotoxic treatment-induced emesis in different animal species.