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。     

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。     

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     

恩丹西酮治疗诱发恶心呕吐的临床观察

本文报导150例以顺铂、阿霉素联合方案化疗的恶性肿瘤患者,应用恩丹西酮与胃复安进行自身随机对照止吐研究。结果提示:恩丹西酮对联合化疗方案引起的急性恶心治疗后的3天内效果明显优于胃复安,分别为71.64％、81.93％与42.28、55.42％(P<0.05),对止吐疗效:恩丹西酮第1、2、3、4天分别为91.04％、86.57％、83.58％和85.07％,后即恢复正常;胃复安到第七天还未恢复正常(95.18％);正常进食在3天内恩丹西酮明显比胃复安效果好(71.16％和87.95％、55.22％和71.08％(<0.05));副反应中恩丹西酮除引起便秘外,其余都比胃复安低(48.0％和64.67％,P<0.05)。资料提示:恩丹西酮在肿瘤患者在化疗时致引起恶心呕吐的效果较理想。     

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。     

恩丹西酮（Ondanstron）预防顺铂呕吐Ⅱ期临床研究

采用自身随机交替对照方法，观察了恩丹西酮的止吐作用。４４例患者入组，顺铂剂量为５０ｍｇ／次，连用３天，患者在第一周期随机接受恩丹西酮或胃复安止吐方案，在第二周期时交替止吐方案。结果显示，恩丹西酮控制急性恶心呕吐优于胃复安方案，９５％的患者有效，而对照组仅５０％有效。恩丹西酮组没有观察到锥体外系症状，而对照组中有３例出现锥体外系症状。     

恩丹西酮（Ondansetron）预防由顺铂引起恶心呕吐Ⅱ期临床研究报告

本文报告４３例接受顺铂化疗肿瘤患者，使用国产恩丹西酮与胃复安随机自身对照止吐研究，结果表明在化疗的第１～３天恩丹西酮组的进食情况及恶心呕吐程度均好于胃复安组、在控制呕吐方面第１、２天恩丹西酮组亦明显的优于胃复安组，ＣＲ＋ＰＲ分别为８１．４％、５８．１％和２７．９％、３２．６％。结果与进口柩复宁疗效相同，能有效地预防顺铂所致的胃肠道反应，尤其在控制顺铂所致的急性呕吐方面，疗效满意，可望取代柩复宁。     

恩丹西酮与胃复安对预防呕吐疗效对比分析

为了观察恩丹西酮与胃复安对预防恶性血液病化疗性呕吐临床疗效，将恶性血液病86例（计206个疗程）随机分为恩丹西酮组（治疗组）和胃复安组（对照组）。治疗组42例（计112个疗程），化疗前用恩丹西酮8mg静脉推注，每疗程2次；对照组44例（计94个疗程）用胃复安20mg加入5％ GS 500mL中静脉滴入，连用5d。结果前者总有效率95．2％（94．6％），急性呕吐有效率84．8％，正常进食率45．2％（42．8％）；后者分别为68．2％（68．1％）、31．9％及6．8％（7．4％）。2组比较差异有极显著性（P＜0．01）。     

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.     

枢复宁防止肿瘤化疗所致呕吐的疗效观察

本文报道用枢复宁防止肿瘤化疗所致呕吐,共计３０例,其中１２例在使用枢复宁前曾用灭吐灵（作为自身对照）。结果发现枢复宁组防止化疗呕吐的完全控制率、有效率均显著高于灭吐灵组（分别是６３．３％１６．７％、９６．７％比５８．３％,Ｐ＜０．００）。且其副作用少而轻微。因此,枢复宁是一种安全而有效的止吐剂。     

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。     

Efficacy of ondansetron against nausea and vomiting caused by dacarbazine-containing chemotherapy.

BACKGROUND AND METHODS. The antiemetic activity of ondansetron (Zofran, Glaxo Pharmaceuticals, Research Triangle Park, NC) was evaluated in 25 patients with recurrent melanoma who were treated sequentially with dacarbazine (DTIC), vinblastine, and cisplatin. The antiemetic regimen included ondansetron alone in 11 patients; ondansetron plus lorazepam (Ativan, Wyeth-Ayerst, Philadelphia, PA) in 9 patients; and ondansetron plus lorazepam plus metoclopramide (Reglan, A. H. Robins Co., Richmond, VA) in 5 patients. Twenty-one patients had no prior exposure to chemotherapy, whereas 4 patients had previously received the same chemotherapy regimen and had severe vomiting despite administration of standard antiemetics. RESULTS. The antiemetic efficacy of ondansetron was impressive. Administration of a single dose of 10 mg resulted in complete control of nausea and vomiting in 22 patients, and the remaining 3 patients had only mild vomiting. CONCLUSIONS. Ondansetron is highly effective in controlling the nausea and vomiting caused by dacarbazine.     

Evaluation of three oral dosages of ondansetron in the prevention of nausea and emesis associated with cyclophosphamide-doxorubicin chemotherapy.

We assessed the antiemetic efficacy and safety of three different oral doses of ondansetron (GR 38032F), a novel serotonin type-3 receptor antagonist, in three consecutive series of 20 breast cancer patients receiving cyclophosphamide-doxorubicin-based chemotherapy for the first time. Patients received oral doses of 8 mg, 4 mg, or 1 mg of ondansetron three times daily for 2 days, with the first dose given 30 minutes before the cyclophosphamide infusion. We then evaluated the efficacy of a conventional antiemetic regimen of intravenous lorazepam, metoclopramide, and diphenhydramine given before chemotherapy and 10 mg prochlorperazine given orally twice on study day 1 and three times on study day 2 in a fourth series of 20 patients with comparable characteristics. The number of emetic episodes, assessment of nausea and appetite, and adverse events were recorded throughout the 2-day study period. Pretreatment and posttreatment clinical laboratory data were also collected. No emesis was observed during the 2-day study period in 17 (85%), 13 (65%), and 11 (55%) patients treated with 8-mg, 4-mg, and 1-mg ondansetron doses, respectively, and in seven (35%) patients who received conventional therapy. The incidence and intensity of nausea were lower with increasing doses of ondansetron and were lower than in the conventional group. Ondansetron-related side effects were generally mild and reversible and did not appear to increase in a dose-dependent manner. These effects included headache, stomach cramps, diarrhea, fatigue, and elevated serum transaminase concentrations. One patient who received three 1 mg doses of ondansetron experienced tremors and muscle twitching. Oral ondansetron is an effective and safe antiemetic for patients receiving noncisplatin cyclophosphamide-doxorubicin-based chemotherapy, and its antiemetic activity appears to be dose-related.     

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     

胃复安联合苯海拉明与昂丹司琼治疗化疗后不良反应的观察

目的将两种化疗止吐方法的疗效进行比较,寻找一种高效价廉的止吐方法。方法将200例恶性肿瘤化疗后呕吐患者随机分为胃复安联合苯海拉明止吐治疗组(100例)和昂丹司琼止吐治疗组100例,观察止吐效果和不良反应。结果对于轻度恶心呕吐者,胃复安联合苯海拉明止吐效果与昂丹司琼相近,差异无统计学意义(P>0.05),但对于重度恶心呕吐者,昂丹司琼止吐效果优于胃复安联合苯海拉明(P<0.05)。结论胃复安联合苯海拉明与昂丹司琼对于轻度呕吐的止吐效果均良好,但胃复安联合苯海拉明较昂丹司琼明显价廉。对于重度呕吐者,昂丹司琼的止吐效果较好。     

Nausea and vomiting after ENT surgeries: A comparison between ondansetron, metoclopramide and small dose of propofol

Aims

To evaluate the antiemetic efficacy of ondansetron, metoclopramide or small dose of propofol following ear, nose and throat (ENT) surgery.

Materials and methods

A prospective randomized study involving 60 patients, both children and adults undergoing elective ENT surgery under standard general anesthesia. At the completion of surgery the patients received either 0.1 mg/kg of ondansetron or 0.2 mg/kg of metoclopramide or 0.5 mg/kg of propofol intravenously. The patients were observed for 24 hrs after operation for any occurrence of nausea and vomiting.

Results

The incidence of postoperative nausea and vomiting (PONV) during first 24 hrs was recorded in 20%, 70%, 50% of patients who had received ondansetron, metoclopr-amide or propofol respectively (p < 0.05). Fewer patients given ondansetron needed rescue antiemetic. The incidence of PONV was higher following middle year surgery.

Conclusion

It was concluded that ondansetron was most effective in preventing occurrence of PONV while metoclopramide was least effective. Propofol was effective only in 50% of patients, thus not recommended for routine use.     

蒽丹西酮防治顺铂化疗引起呕吐的临床Ⅱ期研究

通过对１５例接受顺铂（６０～１００ｍｇ／ｍ２）治疗的恶性肿瘤病人临床研究，探讨抗５－羟色胺类止吐新药—蒽丹西酮的止吐效果。结果证实，第一天止吐率为８６．７％，与枢复宁止吐效果相同（８５％），而明显优于胃复安（３３．３％）；在食欲和进食方面亦优于胃复安；蒽丹西酮价格低，较枢复宁更具有临床应用前景。