Reduced maintenance of complete protection from emesis for women during chemotherapy cycles

Women have a significantly higher rate of chemotherapy-induced emesis. We observed that gender was the important predict factor for reducing the maintenance of complete protection from emesis during chemotherapy cycles. Four hundred patients were enrolled in one of two arms in a crossover fashion. Arm A: three 8-mg doses of ondansetron were given intravenously at 4-hour intervals plus dexamethasone 20 mg intravenously from the start of chemotherapy, followed by dexamethasone 5 mg intravenously every 12 hours. Arm B: as in arm A but with three 8-mg doses of ondansetron intravenously given at 24-hour intervals substituted for ondansetron intravenously given at 4-hour intervals. Rates for complete protection from vomiting/nausea through days 1 to 6 were 69.7%/58.4% for Arm A, and 71.2%/60.9% for Arm B, and 69.0%/60.0% for the first chemotherapy cycle. Risk factors for vomiting and nausea included gender and cisplatin dosage. Complete control of vomiting/nausea for patients without emesis during previous cycle(s) was maintained at 91.4%/86.6%, 91.1%/85.2%, 93.9%/89.9%, 94.7%/92.6%, and 94.9%/94.9% during the second through sixth cycles of chemotherapy, respectively. Complete protection from vomiting and nausea was significantly reduced for female patients (p = 0.048 and p = 0.0004, during the second cycle, and p = 0.0006 and p = 0.0008, during the third through sixth cycles, respectively). The results suggest that women had less maintenance for complete protection from both vomiting and nausea during chemotherapy cycles.     

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.     

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     

Examination on efficacy and safety of concurrent use of ondansetron hydrochloride and steroid in lung cancer patients on cisplatin

The anti-emetic effect and safety in patients receiving ondansetron hydrochloride (OND group) and concurrent use of ondansetron and dexamethasone (DEX group) in cases of acute and delayed onset emesis induced by a single high dose of cisplatin, given as a chemotherapy to lung cancer patients, were comparatively studied. The study subjects were 78 lung cancer patients. The OND group received 4 mg of ondansetron via slow intravenous injection on Day 1, 30 minutes prior to cisplatin, and for Days 2 to 5, the subjects orally received 4 mg ondansetron tablet each day. The DEX group received the same dose regimen of ondansetron as the OND group for Days 1-5, but in addition the subjects received dexamethasone injection in doses of 8 mg twice daily on Day 1 and 4 mg (1 mg QID) daily for Days 2-5. An anti-emetic effect against acute nausea and vomiting was achieved in 83.8% of the OND group and in a higher rate of 94.6% of the DEX group. Significantly better efficacy was seen in the DEX group as to the complete suppression rate of nausea and vomiting and the improvement of food intake. The group also achieved better efficacy in delayed onset of emesis. Two cases of adverse reactions (hiccups and elevation of ALT and BUN) were observed in the DEX group; however, since the symptoms were all mild, we did not consider there was any problem in safety. We conclude from the above findings that concurrent administration of ondansetron hydrochloride and dexamethasone is a clinically useful treatment for acute and delayed onset emesis induced by a single high dose of cisplatin given to lung cancer patients.     

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.     

Examination on efficacy and safety of concurrent use of ondansetron hydrochloride and steroid in gynecological cancer patients on cisplatin]

The anti-emetic effect and safety in patients receiving ondansetron hydrochloride (OND group) and ondansetron and dexamethasone (DEX group) concurrently in cases of acute and delayed onset emesis induced by a single high dose of cisplatin, given as a chemotherapy to gynecological cancer patients, were comparatively studied. The study subjects were 139 gynecological cancer patients. The OND group received 4 mg of ondansetron via slow intravenous injection on Day 1, 30 minutes prior to cisplatin, and for Days 2 to 5, the subjects orally received 4 mg ondansetron tablet each day. The DEX group received the same dose regimen of ondansetron as the OND group for Days 1-5, but in addition the subjects received dexamethasone injection in doses of 8 mg twice daily on Day 1 and 4 mg (1 mg QID) daily for Days 2-5. An anti-emetic effect against acute nausea and vomiting was achieved in 47.9% of the OND group and in a higher rate of 84.2% of the DEX group. Significantly better efficacy was seen in the DEX group also in the complete suppression rate of nausea and vomiting and the improvement of food intake. The group also achieved better efficacy in delayed onset of emesis. Adverse reactions were observed in 2 cases (2 reports of headache) in the OND group and 5 cases (2 reports of hiccups, 2 headache, 2 diarrhea, one constipation, one hot facial flushes and one elevation of gamma-GTP) in the DEX group; however, since the symptoms were all mild, we did not consider there was any problem in safety. We conclude from the above findings that concurrent administration of ondansetron hydrochloride and dexamethasone is a clinically useful treatment for acute and delayed onset emesis induced by a single high dose of cisplatin given to gynecological cancer patients.     

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.     

Randomised comparison of ondansetron plus dexamethasone with dexamethasone alone for the control of delayed cisplatin-induced emesis

The role of 5-hydroxytryptamine₃ (HT₃) antagonists in the treatment of delayed emesis is still controversial. To evaluate whether 5-HT₃ antagonists can add to the efficacy of corticosteroids in controlling delayed emesis, we performed a randomised, prospective, open study comparing ondansetron plus dexamethasone with dexamethasone alone in cisplatin-treated patients. 149 cisplatin-naïve patients with lung cancer received at least 60 mg/m² of cisplatin and were treated with dexamethasone 32 mg intravenously (i.v.) and granisetron 3 mg i.v. on day 1. Patients were randomly assigned to receive either dexamethasone 16 mg i.v. alone (arm A) or dexamethasone plus ondansetron 8 mg daily (arm B) on days 2–4. None of the efficacy variables related to control of delayed emesis differed significantly between the two arms. In conclusion, there does not appear to be sufficient evidence to support the prolonged use of 5-HT₃ receptor antagonists after 24 h of cisplatin-containing chemotherapy.     

32mg恩丹西酮预防化疗所致呕吐的临床效果

[目的]观察32mg盐酸恩丹西酮预防含顺铂方案引起的恶心呕吐的临床疗效和不良反应。[方法]对120例患者采用多中心随机单盲对照试验法，分别用32mg盐酸恩丹西酮和3次8mg盐酸恩丹西酮预防呕吐。[结果]32mg盐酸恩丹西酮和3次8mg盐酸恩丹西酮第一天预防呕吐的有效率分别为85.0％和93.3％(P>0.05)，患者第一天平均呕吐次数分别为2.25±1.57次和1.83±0.96次(P>0.05)。[结论]32mg盐酸恩丹西酮与8mg盐酸恩丹西酮3次给药预防含顺铂化疗方案所致呕吐同样有效。     

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.     

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.     

Stratified, randomized, double-blind comparison of intravenous ondansetron administered as a multiple-dose regimen versus two single-dose regimens in the prevention of cisplatin-induced nausea and vomiting.

PURPOSE: This study compares the efficacy and safety of two single-dose regimens with the approved three-dose regimen of ondansetron in the prevention of cisplatin-induced emesis. PATIENTS AND METHODS: This multicenter study was a stratified, randomized, double-blind, and parallel group design. Chemotherapy-naive inpatients were randomized to receive intravenous (IV) ondansetron (Zofran; Glaxo Inc, Research Triangle Park, NC) 0.15 mg/kg times three doses, every 4 hours or a single 8-mg or 32-mg dose followed by two saline doses that began 30 minutes before cisplatin administration. Cisplatin (high-dose > or = 100 mg/m2 or medium-dose 50 to 70 mg/m2) was given as a single infusion (< or = 3 hours). Patients were monitored for emetic episodes, adverse events, and laboratory safety parameters for 24 hours after cisplatin administration. RESULTS: A total of 699 patients (359 high-dose, 340 medium-dose) were enrolled. Of these, 618 were assessable for efficacy (15 ineligible, 66 protocol deviations). The 32-mg dose was superior to the 8-mg single dose with regard to total number of emetic episodes (high-dose, P = .015; medium-dose, P < .001), complete response (no emetic episodes: high-dose, 48% v 35%; P = .048; medium-dose, 73% v 50%; P = .001) and failure rate (> 5 emetic episodes, withdrawn or rescued: high-dose, 20% v 34%; P = .018; medium-dose, 9% v 23%; P = .005). The 32-mg single dose was also superior to the 0.15 mg/kg times three dose regimen with regard to total number of emetic episodes (medium-dose, P = .033) and failure rate (high-dose, 20% v 36%; P = .009; medium-dose, 9% v 22%; P = .011). Ondansetron was well tolerated. The most common adverse event was headache. An approximate 10-fold increase in the incidence of clinically significant transaminase elevations was observed in the high-dose versus medium-dose cisplatin strata (aspartate aminotransferase [AST], 6.5% v 0.7%; serum alanine aminotransferase [ALT], 5.0% v 0.3%). CONCLUSION: A 32-mg single dose of ondansetron is more effective than a single 8-mg dose and is at least as effective as the standard regimen of 0.15 mg/kg times three doses in the prevention of cisplatin-induced acute emesis.     

恩丹西酮防治顺铂所致呕吐的疗效观察

目的:观察恩丹西酮对顺铂化疗所致呕吐的疗效。方法:随机将186例恶性肿瘤患者分为两组。90例单用恩丹西酮(A组),96例恩丹西酮加地塞米松治疗(B组)。结果:对急性呕吐止吐有效率A、B组分别为85.6%和96.9%。结论:恩丹西酮加地塞米松可显著提高对急性呕吐止吐有效率(P<0.05),但对迟发性呕吐,两组止吐疗效无明显差异(P>0.05)。     

Examination of anti-emetic effect, safety and usefulness of single oral dose of ondansetron tablet in nausea and emesis induced by anti-cancer drugs--dose-finding study of ondansetron tablet in patients receiving non-platinum anti-cancer drugs]

Inhibitory effects on acute nausea and emesis, safety and usefulness of a single oral dose of Ondansetron tablet were evaluated in 3 different dose levels for comparison by telephone registration system, in patients receiving non-platinum anti-cancer drugs. A single dose of ondansetron at 4 mg, 8 mg or 12 mg was given orally at 2 hrs before the initial administration of anti-cancer drugs. The patients were observed for 24 hours after administration of anti-cancer drugs, for occurrence of nausea and emesis. Efficacy rates of inhibitory effects on nausea and emesis were 83.3% (10/12 cases) in 4 mg dose group, 78.6% (11/14 cases) in 8 mg dose group and 84.6% (11/13 cases) in 12 mg dose group, without statistically significant difference. Side effects were observed in 3 cases (headache, cold feeling and trembling in limbs, sleepiness) in 12 mg dose group, but these symptoms were not severe and disappeared after several hours or several days. No abnormality in clinical laboratory findings attributable to Ondansetron was observed. From the above, it was considered that Ondansetron was a clinically useful anti-emetic for nausea and emesis induced by non-platinum anti-cancer drugs and that 4 mg once daily was the optimal dose.     

Randomized double-blind comparison of single high-dose ondansetron and multiple standard-dose ondansetron in chemotherapy-naive pediatric oncology patients.

This prospective, double-blind, randomized study compares the antiemetic efficacy of an equivalent dose of ondansetron administered as a single high dose or as multiple standard doses in pediatric oncology patients. Thirty-one chemotherapy-naive patients were randomized at diagnosis to receive either single high-dose ondansetron (0.6 mg/kg, maximum dose 32 mg) or multiple standard-dose ondansetron (0.15 mg/kg, maximum dose 8 mg, every 4 hr for four doses). Antiemetic efficacy was assessed by an emesis scale described as follows: 1, no nausea or emesis; 2, nauseous but able to eat; 3, nauseous and unable to eat; and 4, emesis. Sixteen patients received high-dose and 15 received standard-dose ondansetron. Patients receiving moderately or severely emetogenic chemotherapy were evenly distributed between the two treatment groups. Eighty-one percent of patients receiving high-dose and 80% receiving standard-dose ondansetron rated 1 or 2 on the emesis scale (p = 0.93). No patient experienced any clinical or laboratory toxicity. Our study suggests that single high-dose ondansetron is as efficacious as the multiple standard-dose regimen and is well tolerated. Its use will facilitate the administration of ondansetron in pediatric patients receiving chemotherapy.     

Prevention of cyclophosphamide/cytarabine-induced emesis with ondansetron in children with leukemia

Ondansetron, a 5HT3 antagonist, was given to 20 children aged 4 to 18 years who were undergoing treatment with the Australian and New Zealand Childhood Cancer Study Group Acute Lymphocytic Leukaemia (ALL) Study V Protocol. The study was open, dose ranging, and noncomparative, and designed to evaluate safety and efficacy of ondansetron in preventing nausea and vomiting caused by cyclophosphamide intravenous (IV) 1,000 mg/m2 day 1, and cytarabine IV subcutaneously (SC) 75 mg/m2 on days 2 to 5. Ten patients were given ondansetron 5 mg/m2 IV (group A) and subsequently another 10 patients were given ondansetron 3 mg/m2 IV (group B). Oral ondansetron was given for 14 doses, at the same dosage for both groups, commencing simultaneously with the IV infusion and continuing at 8 hourly intervals, ie, until day 5. The oral dose was based on surface area with the following schedule: 0.3 to 0.6 m2, 2 mg; 0.6 to 1 m2, 3 mg; and greater than 1 m2, 4 mg. Vomiting on the first day of chemotherapy was reported in group A by one patient and by one patient in group B. Vomiting during days 2 to 5 was reported by two group-A patients and by three group-B patients. Nausea was recorded on day 1 by one patient in group A, and two in group B, and on days 2 to 5 by three patients in group A, and by seven in group B. All patients were alert during treatment with ondansetron and there was no dystonia. There were no changes in renal function or hematology values that could be ascribed to the study drug. Transient elevations in bilirubin and liver enzymes were observed. We conclude that our results indicate that ondansetron is a safe and extremely effective single-agent antiemetic with minimal side effects, when administered both IV and orally.     

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。     

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.     

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.     

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.