A randomized open-label parallel-group study comparing ondansetron with ondansetron plus dexamethasone in patients with metastatic breast cancer receiving high-dose epirubicin. A Hellenic Cooperative Oncology Group study

AIMS AND BACKGROUND: The purpose of this multicenter randomized, open-label, parallel-group study was to assess whether the addition of low-dose dexamethasone to ondansetron results in improved control of chemotherapy-induced emesis in patients undergoing first-line chemotherapy with high-dose epirubicin. METHODS & STUDY DESIGN: Patients were randomized to receive either 24 mg of ondansetron or 24 mg of ondansetron plus 8 mg of dexamethasone administered as an intravenous infusion 30 minutes prior to administration of chemotherapy. Both groups of patients received 8 mg of ondansetron given orally from day 2 to 5 two times daily. Fifty-three patients received ondansetron and 50 received ondansetron plus dexamethasone. The patients recorded nausea and the number of vomits and retches daily on diary cards. RESULTS: Significantly more patients in the ondansetron plus dexamethasone group experienced neither vomiting nor retching during the first day of the first course of chemotherapy compared to those receiving ondansetron alone (79.6% vs 53.8%, P = 0.0062). Furthermore, there was a trend in favor of ondansetron plus dexamethasone in the control of nausea. There was no statistically significant difference between ondansetron plus dexamethasone versus ondansetron alone in protecting patients from emesis between days 2 and 5 of the first course of chemotherapy (66.7% vs 62.7%, P = 0.68). This was probably due to the small sample size. Ondansetron was well tolerated, with 15 patients (15%) reporting adverse events such as headache or constipation. CONCLUSIONS: It appears that ondansetron given intravenously in combination with dexamethasone is more effective than ondansetron alone in the control of acute emesis in patients undergoing their first course of chemotherapy with high-dose epirubicin. No difference between the regimens was found with regard to nausea and delayed emesis control.     

A multicentre, double-blind, randomised trial comparing ondansetron versus ondansetron plus dexamethasone in the prophylaxis of cisplatin-induced delayed emesis

The aim was to compare the efficacy of ondansetron and a combination of ondansetron plus dexamethasone in the prophylaxis of cisplatin-induced delayed emesis over three consecutive courses of chemotherapy. Cancer patients scheduled to receive for the first time cisplatin (>50 mg/m(2)) in combination with other cytotoxic agents, were recruited in a multicentre, randomised, double-blind study and treated with ondansetron 8 mg i.v. and dexamethasone 20 mg i.v. Twenty-four hours after the start of chemotherapy, patients were randomised to treatment either with oral ondansetron 8 mg bd plus placebo on days 2-5 (group A) or with oral ondansetron 8 mg bd plus oral dexamethasone 8 mg bd on days 2-3, and 4 mg bd on days 4 and 5 (group B). Two hundred and thirty-six cancer patients were recruited into the study. Complete protection from delayed vomiting/nausea in group A and group B was Obtained in 50/39% and in 63/42% of patients, respectively in the first course; in 55/34% and in 64/40% in the second and in 49/31% and 60/37% in the third. Logistic regression analysis reveals a statistically significant difference in incidence of emesis between the combination of ondansetron plus dexamethasone and ondansetron alone (P<0.05). The same model, however, shows no difference in incidence of nausea between the two treatment regimens. Ondansetron plus dexamethasone reduces the risk of delayed emesis following cisplatin chemotherapy as compared to ondansetron alone.     

甲泼尼龙合用昂丹司琼防治顺铂引起的急性、迟发性恶心呕吐

目的 :观察甲泼尼龙 (methylprednisolone,甲强龙 )合用昂丹司琼 (恩丹西酮 )治疗以顺铂为主联合化疗引起的呕吐的效果和安全性。方法 :采用随机自身交叉对照方法。 47例患者中 2 3例第 1周期先用甲泼尼龙 80mg和昂丹司琼 8mg ,第 2周期单用昂丹司琼 8mg ;2 4例第 1周期单用昂丹司琼 8mg ,第 2周期用甲泼尼龙 80mg和昂丹司琼 8mg。以上药物均于化疗前 2 0分钟静脉给予 ,每天 1次。每一患者两周化疗药及其剂量相同 (其中顺铂80mg/m2 ) ,止吐药使用天数相同 (一般 2～ 3天 )。结果 :甲泼尼龙合用昂丹司琼和单用昂丹司琼治疗急性呕吐的有效率分别为 93 6 %和 70 2 % (P <0 0 1 ) ,治疗迟发性呕吐的有效率分别为 85 1 %和 65 9% (P <0 0 5) ;对由患者按线性分级计分所得的恶心、食欲、精神状态的疗效合用组明显优于单用组 (P <0 0 1 )。两组治疗不良反应发生率相似且合用组程度较轻。结论 :甲泼尼龙能加强昂丹司琼治疗由大剂量顺铂引起的急性和迟发性呕吐的止吐疗效 ,且能使患者恶心、食欲、精神状态得到明显改善 ,副作用较轻 ,是一较理想的止吐方案     

Comparison of L-758,298, a prodrug for the selective neurokinin-1 antagonist, L-754,030, with ondansetron for the prevention of cisplatin-induced emesis

Substance P is localised in brainstem regions associated with emesis. Based on studies in the ferret, it was postulated that a neurokinin-1 (NK1) receptor antagonist would have antiemetic activity as monotherapy in humans receiving chemotherapy. L-758,298 is a water-soluble, intravenous (i.v.) prodrug for L-754,030, a potent and selective NK1 receptor antagonist. This double-blind, randomised, active-agent (ondansetron)-controlled study enrolled 53 cisplatin-na?ve patients and evaluated the prevention of both acute (0-24 h) and delayed (days 2-7) emesis after cisplatin treatment (50-100 mg/m(2)). All patients received i.v. L-758,298 (60 or 100 mg) (n=30) or ondansetron (32 mg) (n=23) before cisplatin and efficacy was evaluated up to day 7 post-cisplatin. Nausea was assessed by means of a four-point ordinal scale at intervals over the 7 day period. In the acute period, the proportion of patients without emesis in the L-758,298 and ondansetron groups was 37 and 52%, respectively (no significant difference between the groups). Comparing the distribution of average nausea scores over the entire first 24 h revealed no significant difference between the groups. In the delayed period, the proportion of patients without emesis in the L-758,298 and ondansetron treatment groups was 72 and 30%, respectively (P=0.005). The distribution of average nausea scores in the delayed period was lower in the L-758,298 group compared with the ondansetron group (P=0.15 for the entire delayed period and P=0.043 for day 2 only). No serious adverse events were attributed to L-758,298. A single dose of L-758,298 substantially suppressed the delayed nausea and vomiting characteristic of high dose cisplatin and also appeared to reduce acute emesis post-cisplatin. The data also support the proposition that the underlying mechanism(s) of acute and delayed emesis are different.     

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。     

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.     

帕洛诺司琼在鼻咽癌同步放化疗中防治恶心呕吐的疗效观察

目的：对接受同步放化疗的鼻咽癌患者采用帕洛诺司琼预防恶心呕吐,观察其治疗效果。方法将行同步放化疗的鼻咽癌患者80例随机分为2组,分别采用帕洛诺司琼和昂丹司琼止吐治疗,观察并比较2组患者发生急性、延迟性恶心呕吐及其他不良反应的情况。结果帕洛诺司琼组急性恶心发生率为57．5％、急性呕吐32．5％,昂丹司琼组急性恶心、呕吐的发生率为62．5％、35．0％,2组比较差异无统计学意义（P＞0．05）;帕洛诺司琼组延迟性恶心、延迟性呕吐发生率分别为80．0％、62．5％,昂丹司琼组延迟性恶心、呕吐的发生率为87．5％、80．0％,帕洛诺司琼组明显降低,差异有统计学意义（P＜0．05）。除恶心、呕吐的消化道反应外,2组患者均出现头晕、口干、头痛、乏力、低热、便秘、焦虑、腹泻等放化疗相关不良反应,2组的不良反应发生率无明显差异（P＞0．05）。结论对接受同步放化疗的鼻咽癌患者采用帕洛诺司琼,能够预防放化疗引起的急性及延迟性恶心呕吐,尤其是能够有效控制延迟性恶心呕吐的发生,且不良反应轻微,值得在临床上推广使用。     

Control of cisplatin-induced emesis with intravenous ondansetron plus intravenous dexamethasone: a crossover study of triple 8-mg dose of ondansetron

Two hundred seventy-five patients were enrolled in one of two arms in a crossover fashion. Arm A: three 8-mg doses of ondansetron intravenous (IV) were given at 4-hour intervals plus dexamethasone 20 mg IV from the start of chemotherapy followed by dexamethasone 5 mg IV every 12 hours. Arm B: as in arm A but with three 8-mg doses of ondansetron IV were given at 24-hour intervals substituted for ondansetron IV given at 4-hour intervals. There were 237 patients in arm A and 223 patients in arm B. Complete protection from acute and delayed vomiting/nausea obtained in arm A was 94.5%/90.3% and 71.3%/57.8%, respectively; protection obtained in arm B was 92.7%/91.0% and 71.7%/60.5%, respectively. No differences were observed in control of acute emesis after the addition of dexamethasone to ondansetron, given as either a triple 8-mg dose at 4-hour intervals or a single 8-mg dose. The triple dose of ondansetron given at 24-hour intervals was also not more effective than ondansetron given at 4-hour intervals in preventing delayed emesis when dexamethasone was added. However, the former improved control of delayed nausea on day 2. Adverse events tended to be minor, with constipation and hiccup the most common.     

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     

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.     

Prevention of delayed chemotherapy-induced nausea and vomiting after moderately high to highly emetogenic chemotherapy: comparison of ondansetron, prochlorperazine, and dexamethasone

The purpose of this article is to assess the comparative antiemetic efficacy of prochlorperazine, ondansetron, and dexamethasone in the prevention of delayed chemotherapy-induced nausea and vomiting (CINV) after moderately high to highly emetogenic chemotherapy. Cancer patients (n = 232) receiving moderately high to highly emetogenic chemotherapy were randomized to 1 of 3 treatments: 15 mg prochlorperazine spansules twice daily; 8 mg ondansetron tablets twice daily; or 8 mg dexamethasone tablets twice daily on days 2 through 5. All patients received 24 mg ondansetron and 20 mg dexamethasone orally before chemotherapy. Daily assessment (days 1 through 5) included the number of episodes of retching and vomiting, severity of nausea, restlessness, difficulty concentrating and fatigue, treatment satisfaction, and overall quality of life (measured using a 10-cm VAS). The Functional Living Index-Emesis (FLIE) was completed on day 5. Other side effects attributed to antiemetic therapy were recorded daily. For acute CINV, total control, defined as no vomiting, retching, nausea <1 cm on a 10-cm visual analog scale, and no administration of rescue medications, was achieved in 78% in the overall group and was not significantly different in the patients randomized to the 3 treatment arms for delayed CINV. Delayed CINV was reported by 43% to 57% of patients, with the highest incidence reported on day 3. For delayed CINV, patients receiving prochlorperazine reported the lowest average nausea score on days 2 to 5, whereas patients receiving ondansetron reported the highest nausea score (P = 0.05). No statistically significant differences in CINV or side effects of antiemetic therapy were noted between treatment groups on days 2 to 5. For patients similar to those included in this study, there does not appear to be a clinically important difference in efficacy, adverse effects, or treatment satisfaction among dexamethasone, prochlorperazine, and ondansetron in the doses used in these delayed CINV regimens on days 2 to 5 in this study.     

The oral NK(1) antagonist aprepitant for the prevention of acute and delayed chemotherapy-induced nausea and vomiting: Pooled data from 2 randomised, double-blind, placebo controlled trials

In this work, data from two phase III studies were pooled to further evaluate the NK(1) antagonist aprepitant for prevention of cisplatin induced nausea and vomiting. One thousand and forty three patients receiving cisplatin (> or = 70 mg/m2) were randomised to receive either a control regimen (32 mg intravenous ondansetron [O] and 20 mg oral dexamethasone [D] on day 1; 8 mg D twice daily on days 2-4) or an aprepitant (A) regimen (125 mg A plus 32 mg O and 12 mg D on day 1, 80 mg A and 8 mg D once daily on days 2-3, and 8 mg D on day 4). The primary endpoint was no emesis and no rescue therapy. Potential correlations between acute and delayed emesis were assessed, as were frequency of emetic episodes by time interval and effects on nausea and quality of life as measured by the functional living index emesis (FLIE) questionnaire. In the aprepitant group, there was statistically significantly less nausea over the study period as well as higher functioning on the FLIE questionnaire in both the nausea and vomiting domains. Patients without acute emesis were more likely to have no emesis in the delayed phase. Compared with control, the aprepitant regimen improved prevention of delayed emesis by 16% points in patients without acute emesis, and by 17% points in patients with acute emesis. Among patients who did not have complete response, the frequency of emesis at various intervals over 5 days was consistently lower in patients receiving aprepitant. Analyses of this combined Phase III population further characterized the clinical profile of the aprepitant regimen, showing that delayed emesis is correlated with, but not entirely dependent on, the presence of acute emesis, and that aprepitant has a favorable effect against nausea throughout 5 days postchemotherapy. In addition, even among patients who had emesis or needed rescue therapy, aprepitant was associated with a lower frequency of these events compared with the control regimen.     

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)     

思密达在预防顺铂所致迟发性恶心呕吐反应中的作用

目的：探讨思密达在肿瘤化疗所致消化道反应中的应用价值。方法：对５４例接受顺铂联合方案化疗的恶性肿瘤病人进行止吐治疗观察。于化疗第一周期或第二周期使用思密达加枢复宁止吐,同一病人于另一周期只用枢复宁作自身对照,思密达每次３．０ｇ,每日３次于化疗前一天开始连服５ｄ。结果：两种止吐方法对化疗后２４ｈ内急性恶心呕吐有效率无差异,化疗后２￣５ｄ,观察组恶心和呕吐有效率均高于对照组（Ｐ〈０．０１）,观察组恶心     

A randomized double-blind comparison of ondansetron and metoclopramide in the prophylaxis of emesis induced by cyclophosphamide, fluorouracil, and doxorubicin or epirubicin chemotherapy

Seventy-five breast cancer patients scheduled to receive a first course (in a new cycle) of cyclophosphamide, fluorouracil, and doxorubicin (FAC) or epirubicin (FEC) participated in a double-blind crossover study to compare the antiemetic efficacy and safety of ondansetron (GR38032), a 5-hydroxytryptamine3 (5-HT3) receptor antagonist, and metoclopramide. Ondansetron was given as an 8 mg loading dose (4 mg intravenously [IV] plus 4 mg orally) before chemotherapy followed by 8 mg every 8 hours orally for 3 to 5 days. Metoclopramide was given as an 80 mg loading dose (60 mg IV plus 20 mg orally) before chemotherapy followed by 20 mg every 8 hours orally for 3 to 5 days. A "period" interaction in the analysis of emetic response in the first 24 hours necessitated a parallel group analysis of first treatments only, 68 patients being assessable for this parameter. In the first 24 hours, complete or major control (zero to two emetic episodes) of emesis was achieved in 30 of 35 (86%) patients receiving ondansetron and in 14 of 33 (42%) patients receiving metoclopramide (P less than .001). Ondansetron was also more effective in reducing acute nausea. On days 2 to 3, the complete or major responses were significantly better with ondansetron (81% v 65%; P = .033), but there was no statistical difference in the control of nausea. There was a significant patient preference for ondansetron (63% v 26%; P = .001). Extrapyramidal reactions were observed in two metoclopramide treatments; both treatments were otherwise well tolerated. These results are consistent with serotonin (5-HT), being a significant neurotransmitter of cyclophosphamide/doxorubicin- or epirubicin/fluorouracil-induced emesis.     

Antagonism of serotonin S3 receptors with ondansetron prevents nausea and emesis induced by cyclophosphamide-containing chemotherapy regimens

The control of nausea and emesis in cancer patients receiving chemotherapy poses a significant management problem. In this randomized, double-blind, placebo-controlled study, we evaluated the effect of serotonin S3 receptor blockade with ondansetron (GR 38032F) on the prevention of nausea and vomiting induced by cyclophosphamide-containing chemotherapy. Cyclophosphamide was given in doses of 500 to 600 mg/m2 and ondansetron as three intravenous (IV) doses of 0.15 mg/kg. Most patients had breast cancer. Cyclophosphamide was given in combination with doxorubicin (65% of patients) or with fluorouracil (85% of patients: 50% with Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH] and 35% with methotrexate). All placebo-treated patients experienced vomiting, whereas 70% of patients treated with ondansetron did not vomit (P = .008). Median nausea scores were 8 mm on ondansetron and 65 mm on placebo (P less than .001). Seventy percent of patients treated with ondansetron retained their normal appetite, compared with 10% of placebo patients. Adverse events occurred in six placebo patients and one ondansetron patient. Diarrhea and headache were the most common events, both occurring more frequently in the placebo group. There were no extrapyramidal reactions, and the only significant biochemical change occurred in a placebo-treated patient. These results suggest that serotonin S3 receptor antagonists represent a novel, effective, and safe mode of therapy for nausea and emesis induced by cyclophosphamide-containing chemotherapies. In addition, our observations are compatible with the view that serotonin, acting on S3 receptors, mediates the nausea and emesis occurring after cyclophosphamide chemotherapy.     

Ondansetron for the prevention of emesis induced by high-dose cisplatin. A multi-center dose-response study

To determine a dose-response relationship of ondansetron for the prevention of emesis induced by high-dose cisplatin and to study the efficacy of the extended dosing schedule of ondansetron during 20 hours after cisplatin administration, 36 patients with malignant neoplasms who had not previously received chemotherapy but who were currently receiving cisplatin were treated. These patients received a six-dose regimen of 0.01 mg/kg (low dose) or 0.18 mg/kg (high dose) of ondansetron. Seven (41%) patients in the high-dose group had no emesis and four (24%) patients had one or two episodes. One (5%) patient in the low-dose group had no emesis and four (21%) patients had one or two episodes. The difference in the number of emetic episodes was significant (P less than 0.02). Fifty percent of the high-dose patients reported no nausea or mild nausea, compared with 11% of the low-dose patients. Clinical adverse events included mild, transient headache and dizziness in the high-dose group and headache and diarrhea in the low-dose group, with no significant laboratory abnormalities. There is a parallel relationship between the ondansetron doses and the antiemetic efficacy. The response rate for the six-dose regimen of 0.18 mg/kg was not superior to that for the previously reported 0.18 mg/kg regimen given in a three-dose schedule in a similar clinical setting.     

Ondansetron plus dexamethasone is superior to ondansetron alone in the prevention of emesis in chemotherapy-naive and previously treated patients

BACKGROUND: This prospective, randomized, double-blind study assessed whetherthe addition of dexamethasone to ondansetron leads to improvedcontrol of chemotherapy - induced emesis, both in patients undergoingtheir first course of highly emetogenic chemotherapy and inchemotherapypretreated patients refractory to standard anti-emetics. PATIENTS AND METHODS: Patients were randomized to receive either 20 mg dexamethasoneas an intravenous infusion or placebo plus ondansetron 8 mg15 minutes prior to and 4 and 8 hours after the administrationof chemotherapy. According to the randomisation code patientsreceived from day 2 to day 5 either ondansetron 8 mg p.o. +placebo p.o., three times daily, or ondansetron 8 mg p.o. +dexamethasone 4 mg p.o., three times daily. Patients undergoingmultiple-day treatment received intravenous study treatmenton the days of chemotherapy and thereafter oral treatment asoutlined above. RESULTS: A total of 215 patients were entered into the study. Of these,207 were evaluable (111 previously-untreated and 96 previously-treatedpatients). In the chemotherapynaive patients the combinationof ondansetron plus dexamethasone was significantly superiorto ondansetron plus placebo in protecting the patients completelyfrom emesis (retching and vomiting) (81% versus 64%, p –0.04). The mean number of vomiting episodes was significantlylower in the ondansetron-plus-dexamethasone-treated patientsthan in those receiving ondansetron plus placebo (0.8 versus2.1, p – 0.03). In this group of patients there was significantlysuperior protection from emesis on the second day (pvalue –0.04), and a trend towards a better protection on the thirdand fourth days. On each day the active combination offeredbetter protection from nausea with an approximately 20% differencein favor of ondansetron plus dexamethasone. In the group ofestablished vomiters the combination of ondansetron plus dexamethansonewas superior to ondansetron plus placebo in protecting the patientsfrom acute emesis, with 70% versus 48% of the patients beingcompletely protected (p = 0.03). The mean number of vomitingepisodes was significantly lower in the ondansetron-plusdexamethasone-treated-patientsthan in those receiving ondansetron plus placebo (0.9 versus2.1, p = 0.02). In the ondansetron-plus-dexamethasone arm 55%of the patients had complete protection from nausea, retchingand vomiting compared to 35% in the ondansetron-plus-placebo-treatedgroup (p = 0.05). Overall 22% of the patients (20% in the ondansetronplus-placeboand 25% in the ondansetron-plus-dexamethasone arm) experiencedat least one, usually mild, adverse event. More patients inthe ondansetron-plus-dexamethasone arm complained of epigastricpain or burning (8/101 versus 4/112, p-value = 0.16). The differencein patients reporting constipation (6/101 versus 0/112) washighly significant at a p-value of 0.008. CONCLUSIONS: The combination of dexamethasone plus ondansetron is more effectivein protecting chemotherapynaive patients undergoing their firstcourse of highly emetogenic chemotherapy with cisplatin andchemotherapy-pretreated patients refractory to standard antiemeticsfrom chemotherapy-induced nausea and vomiting compared to ondansetronplus placebo. nausea, vomiting, chemotherapy, ondansetron, dexamethasone, delayed emesis     

Clinical usefulness of ondansetron hydrochloride for nausea and vomiting during repeated courses of chemotherapy for malignant lymphoma--impact of prognosis announcement on anti-emetic effect and evaluation of patient perception of chemotherapy-associated adverse events

We evaluated the efficacy and safety of ondansetron hydrochloride (OND) on nausea and vomiting during repeated courses of CHOP or ACOMP-B therapy in patients with malignant lymphoma. The impact of the prognosis announcement on the anti-emetic effect and chemotherapy-associated adverse events was also investigated. Forty-two subjects with malignant lymphoma who underwent CHOP or ACOMP-B therapy including cyclophosphamide 600 mg/m2 and adriamycin 40 mg/m2 were investigated for a maximum of 6 courses. For acute nausea and vomiting, ondansetron was injected intravenously before the start of chemotherapy on the first day of each course of chemotherapy. For delayed emesis, ondansetron was administered orally for 4 days from the following day. The efficacy on acute nausea and vomiting was found to be 95.0% (1st course), 95.0% (2nd course), 90.9% (3rd course), 88.2% (4th course), 92.3% (5th course) and 91.7% (6th course), respectively. A high efficacy of > or = 85% was also obtained for delayed nausea and vomiting on each day. Though the adverse event of elevated GPT value developed in one subject. It was mild and resolved. No difference in efficacy was seen with or without announcement of prognosis to patients. Following the investigation on antiemetic effect, patient perception of chemotherapy-induced adverse events was evaluated. The most common event was hair loss, followed by taste abnormality and numbness and hyposthesia of the tips of the fingers. The incidence of nausea and vomiting was the 4th and 5th most common, which are less frequent than in the report of Coates in 1983. In conclusion, ondansetron is considered clinically useful with stable anti-emetic effect on both acute and delayed nausea and vomiting over repeated courses of chemotherapy, without any significant safety problem.