The effectiveness of a single intravenous dose of ondansetron.

This paper reviews data from 3 randomised, double-blind, parallel-group studies carried out in patients receiving high-dose cisplatin chemotherapy (50-120 mg/m2). These comparative trials show that a single intravenous dose of ondansetron (8-32 mg) is as effective as the continuous infusion and intermittent dose regimens used in previous clinical trials (8 mg i.v. followed by a 1 mg/h infusion for 24 h and 0.15 mg/kg i.v. x 3). One of the studies, carried out in Europe, demonstrated that a single 8 mg i.v. dose was as effective as 32 mg given either as an 8 mg loading dose followed by an infusion or as a single intravenous dose of 32 mg before chemotherapy. A similar study conducted in the United States showed that a 32 mg i.v. single dose was significantly more effective than both the 8 mg i.v. dose and the intermittent dose schedule. This study used a prospective stratification based on the dose of cisplatin (50-70 mg/m2 and greater than or equal to 100 mg/m2). In both strata the 32 mg dose was superior. These results emphasise the importance of selecting the dose of ondansetron (8-32 mg) based on factors that predispose patients to emesis, e.g., female gender, patients with a history of chemotherapy or motion sickness and the dose of cisplatin. The ondansetron dosing regimen for patients receiving a highly-emetogenic chemotherapy (8-32 mg i.v. followed by 8 mg orally twice daily) is both simple and flexible.     

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.     

A randomized trial of high dose bolus metoclopramide versus low-dose continuous infusion metoclopramide in the prevention of cisplatin-induced emesis

We compared the antiemetic efficacy of metoclopramide in a bolus low-dose infusion schedule to that of metoclopramide given in a conventional high-dose bolus schedule in a randomized crossover trial. Thirty-two treatment courses in 16 patients receiving cisplatin chemotherapy were evaluable. The metoclopramide regimen was either 2 mg/kg i.v. bolus, then 20 mg/h by infusion for 4 h, or 2 mg/kg i.v. bolus every 2 h for three doses. Dexamethasone 20 mg i.v. and diphenhydramine 50 mg i.v. were also given. Antiemetic efficacy was assessed by a questionnaire. There were no differences in antiemetic efficacy between the metoclopramide regimens. With either program, 75% of patients were emesis-free, 13% had mild symptoms, and 13% had moderate symptoms (greater than two emetic episodes). The infusion metoclopramide regimen was 30% less expensive than the bolus schedule in our pharmacy. Thus, we recommend low-dose metoclopramide infusion as a less expensive, equally effective alternative to high-dose bolus regimens for antiemetic treatment.     

Comparative efficacy of a single oral dose of ondansetron and of buspirone against cisplatin-induced emesis in cancer patients.

Buspirone, an agonist of the 5-HT1A subtype of serotonin receptors, has shown antiemetic activity in animal models. However, in cancer patients treated with cisplatin, ondansetron, given either i.v. (one 8-mg dose 30 min after cisplatin) or orally (one 16-mg dose at the end of cisplatin infusion) was superior (P < 0.001) to buspirone (60 mg p.o. at the end of cisplatin and 60 mg p.o., 30 min later), in all parameters of antiemetic efficacy. These results are in favour of 5-HT3 receptors, but against the participation of 5-HT1A receptors in acute emesis associated with cisplatin chemotherapy.     

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.     

Antiemetic effects of combinations of metoclopramide, droperidol and dexamethasone for the prevention of cisplatin-induced gastro-intestinal toxicity: a randomized crossover trial

Thirty-two patients with primary lung cancer receiving combination chemotherapy including cisplatin at a dosage of 80-120 mg/m2 were entered into an antiemetic randomized crossover trial. Patients received metoclopramide (2 mg/kg i.v. every 2 h X 5), droperidol (0.5 mg/kg i.v.) and dexamethasone (30 mg i.v.) on day 1, and metoclopramide (1mg/kg i.v. every 8 h X 3) (Regimen A) or metoclopramide and droperidol (2.5 mg i.v. every 8 h X 3) (Regimen B) on days 2 to 5. No vomiting occurred within the first 24 hours after cisplatin administration in 75% of patients. Regimen B was found to be more effective than regimen A with respect to the mean duration of vomiting (p less than 0.1), the mean duration of nausea (p less than 0.05), the mean duration of anorexia (p less than 0.05), and the mean score of the patients' opinions (p less than 0.1). When the patients were asked for their opinion of the two regimens, 39% preferred regimen B (p less than 0.05). There were no major side effects with either regimen.     

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.     

A comparison of ondansetron with alizapride plus methylprednisolone in the control of cisplatin-induced emesis. The French Pneumology Group for the Ondansetron Study.

This randomised, single-blind, parallel-group study was carried out in 48 French pneumology centres to compare the anti-emetic efficacy of ondansetron and an alizapride plus methylprednisolone (ALI/MPS) combination in patients receiving high-dose cisplatin. A total of 220 patients were recruited of whom 209 were evaluable (100 on ondansetron and 109 on ALI/MPS). Thirty minutes before cisplatin, patients received either ondansetron (8 mg i.v.) or alizapride (4 mg/kg i.v.) combined with methylprednisolone (500 mg i.v.). The ondansetron and alizapride injections were repeated 4 and 8 h later. Thereafter, patients received oral ondansetron (8 mg) or alizapride (50 mg) 3 times daily for 5 days. Ondansetron was significantly superior to ALI/MPS in the control of acute emesis (p less than 0.001); 88/100 (88%) of ondansetron, and 69/109 (63%) of ALI/MPS patients experienced less than 3 emetic episodes. Similarly, ondansetron was superior to ALI/MPS for the control of acute nausea (visual analogue scale at 24 h; 13 vs. 22 mm respectively, p = 0.0012). The superiority of ondansetron over days 2-6 was not as great as that over the first 24 h, although there was a trend in favour of ondansetron. More patients treated with ondansetron wished to take the same anti-emetic treatment again (83% for ondansetron vs. 56% for ALI/MPS, p less than 0.001). Both treatments were well tolerated. This study shows that ondansetron is superior to a benzamide-corticosteroid combination in the control of acute cisplatin-induced emesis.     

Treatment of nausea and vomiting induced by a 24-hour i.v. infusion of cisplatin

Nine advanced gastric cancer patients were given 17 courses of cisplatin administrations by means of a 24-hour intravenous infusion at a dose of 100 mg/m2. For an anti-emetic, 40 mg of metoclopramide was administered 5 times at 6-hour intervals, along with a 500 mg hydrocortisone administration at the start of the cisplatin infusion. Despite this preventative treatment, nausea and/or vomiting occurred in over one-third of all the courses. Thus, to combat this nausea and/or vomiting, a combination of lorazepam (1.5 mg/day, divided into 3 p.o.), dexamethasone (20, 10 and 10 mg by i.v. at 3, 8, and 24 hours, respectively, after start of the cisplatin infusion), and a 60 mg intravenous administration of metoclopramide (5 times at 6-hour intervals) was given, and it was found that this new method (Method IV) prevented both nausea and vomiting.     

GRANISETRON COMPARED WITH ONDANSETRON PLUSDEXAMETHASONE IN THE PREVENTION OF NAUSEAAND VOMITING INDUCED BY A INTENSELYEMETOGE

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

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

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.     

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.     

Pharmacokinetic study of gemcitabine, given as prolonged infusion at fixed dose rate, in combination with cisplatin in patients with advanced non-small-cell lung cancer

Introduction

Although some studies have suggested that gemcitabine delivered as a fixed dose rate (FDR) infusion of 10 mg/m²/min could be more effective than when administered as the standard 30-min infusion, the available pharmacokinetic data are still too limited to draw definitive conclusions. This study is aimed to investigate the plasmatic and intracellular pharmacokinetics of gemcitabine given as FDR at doses of 600 and 1,200 mg/m² in combination with 75 mg/m² of cisplatin in advanced non-small-cell lung cancer (NSCLC) patients.

Patients and method

The patients were divided into two groups receiving different initial doses of the drug: 4 patients received 600 mg/m² gemcitabine 60-min i.v. infusion and 4 patients 1,200 mg/m² gemcitabine 120-min i.v. infusion both as a FDR of 10 mg/m²/min on days 1 and 8 of a 21-day cycle (at first cycle). At the second cycle, all patients were treated with gemcitabine at 1,200 mg/m² 120-min i.v. infusion (FDR of 10 mg/m²/min) on days 1 and 8 of a 21-day cycle. At each cycle, gemcitabine was administered alone on day one, and in combination with 75 mg/m² of cisplatin on day 8. Plasmatic and intracellular pharmacokinetic analyses were performed on blood samples collected at defined time points before, during and after gemcitabine infusion.

Results

The plasmatic pharmacokinetic parameters were clearly different when the patients received a higher gemcitabine dose in the second cycle compared to the lower dose of the first course; in the same time, the intracellular drug levels were not modified. Comparing the pharmacokinetic parameters of different patients treated at different dose levels, the results appeared to be quite similar.

Conclusions

A substantially higher accumulation of metabolites in peripheral blood mononuclear cells was observed when the longer infusion time was employed, suggesting a pharmacological advantage for this treatment schedule.     

Comparison of ramosetron and granisetron for the prevention of acute and delayed emesis in Cisplatin-based chemotherapy: a randomized controlled trial

OBJECTIVE: A clinical study of ramosetron was carried out to evaluate its efficacy in preventing both acute and delayed emesis in cisplatin-based chemotherapy by using a double-blind method with granisetron as the comparative drug. METHODS: Cisplatin at a dose of > or =70 mg/m(2) was administered as a single intravenous (i.v.) infusion over 4 h. Patients were randomly assigned to receive either ramosetron (0.3 mg i.v. bolus 30 min before cisplatin on Day 1 and a 0.1 mg tablet in the morning for Days 2 to 5 after completion of chemotherapy; n = 36) or granisetron (3 mg i.v. infusion 30 min before cisplatin on Day 1 and a 1 mg tablet in the morning for Days 2 to 5 after completion of chemotherapy; n = 37). The observation period started with the initiation of chemotherapy (0 h) and continued for 24 h after completion of the chemotherapy for acute emesis, and on Days 2 to 5 for delayed nausea and vomiting. RESULTS: A total of 73 patients were eligible for evaluation, with 36 patients in the ramosetron group and 37 in the granisetron group. The efficacy of both drugs was analyzed in terms of the degree of achievement in each day of treatment. Ramosetron was as effective as granisetron in preventing nausea and vomiting (both acute and delayed emesis). The two drugs had a similar safety profile and adverse events were generally mild and transient. CONCLUSIONS: Ramosetron is effective and safe for the control of acute and delayed emesis induced by cisplatin.     

Antiemetic efficacy of droperidol or metoclopramide combined with dexamethasone and diphenhydramine. Randomized open parallel study

We have performed an open parallel randomized study of the efficacy of two antiemetic drug combinations. Dexamethasone (10 mg i.v.), diphenhydramine (25 mg i.v.), and metoclopramide (3 mg/kg, 15 min i.v.) or droperidol (1.25 mg slow push) were given 30 min before and 90 min after start of chemotherapy. Thirty-six patients treated with cisplatin-based regimens (30 mg/m2 x 3 days or 60 mg/m2 day 1 only), have been observed for 48 h after their last chemotherapy. Twelve (67%, confidence interval 95%: 41-87%) experienced no vomiting while on metoclopramide and 11 (61%, confidence interval 36-83%) were protected by droperidol. Further patient accrual was stopped because of side effects in one study arm. Moderate sedation (difficulty to keep up a conversation) was observed in 48% of those on metoclopramide versus 14% of those on droperidol (p less than 0.05). We conclude that low-dose droperidol combinations can offer antiemetic protection for patients treated with moderate-dose cisplatin-based chemotherapies. In view of the potential for severe long-term neurologic problems due to metoclopramide or droperidol, these and similar drugs should be used at the lowest possible dose.     

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.     

Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron.

BACKGROUND: Although all first-generation 5-HT(3) receptor antagonists demonstrate efficacy in preventing acute chemotherapy-induced nausea and vomiting (CINV), effective prevention of delayed CINV has not yet been achieved. This study compared the efficacy and tolerability of palonosetron, a novel, second-generation 5-HT(3) receptor antagonist, with ondansetron. PATIENTS AND METHODS: In this multicenter, randomized, double-blind, stratified, phase III study, 570 adult cancer patients were randomized to receive a single i.v. dose of palonosetron 0.25 mg, palonosetron 0.75 mg or ondansetron 32 mg, each administered 30 min before initiation of moderately emetogenic chemotherapy. The primary end point was the proportion of patients with no emetic episodes and no rescue medication [complete response (CR)] during the 24 h after chemotherapy administration (acute period). Secondary end points included efficacy in treatment of delayed CINV (相似文献   

High-dose oral and intravenous metoclopramide in doxorubicin/cyclophosphamide-induced emesis. A randomized double-blind study

Emesis remains a major side effect of cancer chemotherapy. High-dose intravenous metoclopramide has proved to be effective antiemetic therapy for cisplatinum induced emesis. It has not been rigorously tested in nonplatinum chemotherapy. This double-blind, noncrossover, randomized trial compared high-dose oral and intravenous metoclopramide to standard oral prochlorperazine in emesis caused by doxorubicin [70 mg/m2 body surface area (BSA)] and cyclophosphamide (700 mg/m2 BSA). Prochlorperazine (10 mg/dose), oral metoclopramide, and intravenous metoclopramide (2 mg/kg/dose each) were given 30 min before chemotherapy and then every 4 h for 24 h. Ten patients were randomized to prochlorperazine therapy, 10 to oral metoclopramide, and 9 to i.v. metoclopramide. Median number of emeses for the first chemotherapy cycle was 3, 3, and 7 for prochlorperazine, oral, and i.v. metoclopramide, respectively. Statistical analysis showed no significant advantage of any regimen (p greater than 0.4). For patients who continued the antiemetic study, frequency of emesis increased with each successive cycle of chemotherapy. Six of 19 patients treated with metoclopramide developed dystonic reactions compared with zero of 10 on prochlorperazine. High plasma metoclopramide levels were achieved with both metoclopramide regimens and did not correlate with frequency of emesis. High-dose oral and i.v. metoclopramide in an every 4 h regimen did not show any advantage over standard antiemetic therapy for doxorubicin/cyclophosphamide-induced emesis and were associated with significant toxicity.     

GR38032F,a 5HT3 receptor antagonist,in the prophylaxis of acute cisplatin-induced nausea and vomiting

Summary A total of 28 patients receiving cancer chemotherapy with cisplatin-containing regimens (70–120 mg/m²) participated in an evaluation of the efficacy and safety of GR38032F for the prevention of acute nausea and vomiting. GR38032F, a 5HT₃ receptor antagonist, was given 30 min prior to cisplatin as an 8-mg loading dose by i.v. infusion over 15 min, followed by continuous infusion at a rate of 1 mg/h for 24 h. Efficacy was assessed by measurement of the number of episodes of retching and vomiting occurring in the 24 h after cisplatin administration and by an assessment of nausea during the same period. In all, 26 patients were evaluable for efficacy: overall, complete control was achieved in 12 patients (46%), major control (1–2 emetic episodes), in 6 (23%); minor control (3–5 episodes), in 1 (4%); control could not be achieved (failure; >5 episodes) in 7 patients (27%). GR38032F was well tolerated, with no significant drug-related adverse events. These encouraging results should be confirmed in compariative trials.