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Objective: To justify the use of ondansetron as a preventive treatment for postoperative nausea and vomiting (PONV) of adults and children in neurosurgery., Study Design: Meta-analysis., Patients and Methods: Six published, randomized, double-blinded, placebo-controlled trials were selected to study the efficacy of ondansetron on PONV in adults undergoing craniotomy. Similarly, three studies were selected in children. The treated adults received 4 or 8 mg of ondansetron during the peroperative period. As for children, they were given a repeated dose of 0.15 mg/kg of ondansetron. The emetic episodes noted for 24 hours in children and until 48 hours in adults were analyzed. The results were presented as relative risks (RR) following a fixed model and a 95% confidence interval (CI). The test for heterogeneity was measured with the I(2) Altman DG test., Results: At 24 hours, among the 308 adults tested, nausea and vomiting were significantly reduced by 22% and 57%, respectively; no significant reduction in vomiting was noted for the 149 children patients. At 48 hours, no significant modification was observed in adults., Conclusions: Peroperative intravenous dose of ondansetron 4 mg in neurosurgery in adults is required to prevent PONV during the first postoperative 24 hours. However, further studies are needed to determine best time and dose infusion to prolong clinical efficacy., (Copyright 2009 Elsevier Masson SAS. All rights reserved.)

The objective of this double blind parallel-group multicentre study was to compare the efficacy and safety of the combination ondansetron + methylprednisolone + lorazepam (O + M + L) in the prevention of emesis induced by chemotherapy with cyclophosphamide or adriamycin . This tritherapy was compared to a bitherapy O + M. Patients included were suffering from severe haemopathy or breast cancer. They had to have an incomplete response to a previous antiemetic association of 5HT3 serotoninergic receptor antagonist and corticoid. One hundred and thirty-five adult patients were included and were randomised to receive : O + M + L or O + M for 3 days. The emesis control during the 3 days of treatment (no emetic episode during the complete course) was significantly superior in the group O + M + L than in the group O + M (69% versus 46%, p = 0. 042); nausea control on the worst day of the cure was significantly superior in the group O + M + L than in the group O + M (p = 0.04) with 76% of patients in the group O + M + L having complete or major nausea control compared to 51% in the group O + M. The stability of quality of life during the days following chemotherapy measured by one questionnaire, including two scales, one cancer specific (FLIC) and one emesis specific (FLIE), appeared significantly better in group O + M + L (p = 0.04 and p = 0.019). Safety of both antiemetic regimens was good and similar between the two treatment groups. This trial shows that the adjunction of lorazepam to ondansetron and corticoid in combination increases the antiemetic control for patients with an incomplete response to a previous regimen containing a 5HT3 serotoninergic receptor antagonist and a corticosteroid in the prevention of chemotherapy-induced emesis.

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.

Objective: To determine the effect of ondansetron on intracranial pressure (ICP), mean arterial pressure (MAP) and cerebral perfusion pressure (CPP)., Study Design: Prospective, comparative, randomized double-blind study., Patients: Twenty-six patients undergoing intracranial surgery., Method: Induction was obtained with propofol (1-2.5 mg.kg-1), fentanyl (1.5 micrograms.kg-1) and pancuronium (0.1 mg.kg-1), and maintenance was achieved with propofol and fentanyl. Intermittent positive pressure ventilation was used to ensure mild hypocapnia at 35 +/- 2 mmHg. Positioning of the patient was followed by 15 minutes steady-state. Patient received thereafter either 8 mg ondansetron or a placebo intravenously. The ICP was measured using a lumbar malleable spinal needle. CPP was calculated using the formula CCP = MAP-ICP. All variables were measured every minute for 15 minutes., Results: The ICP, MAP and CPP did not differ between the two groups. There were no differences in the highest ICP values in patients receiving either ondansetron or placebo (11 +/- 5 versus 9 +/- 5, mean +/- SD), respectively., Conclusion: Intravenous administration of 8 mg ondansetron affects neither cerebral hemodynamics nor ICP.

This multicentre randomized single-blind parallel group study compared the efficacy of oral ondansetron plus methylprednisolone (OND+MPS) with conventional antiemetic strategies (TH) over 4 consecutive courses in moderately emetogenic chemotherapy. This study was conducted in naive patients receiving a minimum of 3 cytotoxics including adriamycin (> or = 35 mg/m2) and cyclophosphamide (> or = 500 mg/m2) plus an other alkylating agent. Of the 364 patients included in the study, 70% had a breast cancer and 30% a lymphoma. Patients were divided into two groups. On day 1, one group of patients received OND (8 mg, po) 2 hours before chemotherapy, followed by a slow intravenous injection of MPS (120 mg) 30 minutes before chemotherapy. Eight hours after the start of chemotherapy, patients received OND (8 mg, po) and MPS (16 mg, po). On days 2-4, patients received OND (8 mg, po) and MPS (16 mg, po) twice daily. The second group of patients received conventional antiemetic treatment (benzamide plus corticosteroids with or without benzodiazepins). The primary efficacy parameter was defined as complete control of emesis (0 emetic episodes) over 4 consecutive courses of chemotherapy. In the OND+MPS group, 63% of patients experienced complete control of emesis versus 33% in the TH group (p < 0.001). The secondary parameters (percentage of days with no emetic episodes, control of emetic episodes, grade of nausea at each course, patient preference and quality of life evaluation) were always significantly better in the OND+MPS treated group. The percentage of days without any emetic episode over the 4 courses of chemotherapy was 91% in the OND+MPS group and 75% in the TH group (p < 0.001). Ninety-two percent of patients from OND+MPS group preferred to continue their treatment versus 76% in the TH group (p < 0.001). Concerning the quality of life assessed by FLIC and FLIE questionnaires, the analysis showed a significant difference at the end of the treatment in favor of OND+MPS (p = 0.037 and 0.0075 respectively). This study showed the interest in using the combination OND+MPS right from the first course of moderately emetogenic chemotherapy.

Chemotherapy-induced emesis is dependent not only on individual parameters but also on treatment parameters (type and dose of the cytotoxic drug, combination with other cytotoxic drugs). Cyclophosphamide-based chemotherapy is potentially emetogenic and the emtogenicity is proportionally dependent on the dose. Therefore, the preventive antiemetic treatment must be adapted to this emetogenic risk. A number of studies have assessed the efficacy of ondansetron, a highly selective 5-HT3 receptor antagonist, for the control of 'non cisplatin' chemotherapy. In mild emetogenic regimens, oral ondansetron is more effective than placebo and its efficacy is similar to the classic antiemetic regimen metoclopramide-dexamethasone. Concerning moderately emetogenic chemotherapies, iv ondansetron is highly effective and its effecicay is superior to that of metoclopramide and alizapride. Delayed nausea and vomiting can be controlled by an oral ondansetron treatment. This allows to maintain the good response obtained by the initial antiemetic regimen. With very high doses of cyclophosphamide, as in conditioning chemotherapy and total body irradiation prior to bone marrow transplantation, no optimal antiemetic treatment has still been defined; but the combination of ondansetron with dexamethasone should be used according to the poor control obtained with ondansetron alone. However, studies combining 5-HT3 receptor antagonists with dexamethasone are warranted in order to define the optimal treatment in this particularly emetogenic treatment setting.

The treatment of cancer patients has improved over the few past years. The improvement includes new chemotherapy modalities and the new treatments for side effects. The introduction over the last 5 years of 5-HT3 receptor antagonists, a recent class of antiemetic agents, and hematopoietic growth factors, has allowed oncologists to improve success rates and survival of cancer patients, by developing new cytotoxic agents and increasing drug doses and/or modifying the design and administration of conventional chemotherapy treatment schedules. At present, dose-intensifications of several cytotoxic agents are available. Pharmacomodulation with 5 FU and folinic acid is more emetogenic than 5 FU alone. In contrast, chronomodulation seems to be less emetogenic. For new cytotoxic agents and oral chemotherapy, the emetogenic potential differs according to the drug and the antiemetic treatment must be therefore adapted to each situation.

This study was performed in a group of 89 patients treated for breast carcinoma with a FEC regimen (5-fluorouracil, epirubicin, cyclophosphamide). The aim was to evaluate the antiemetic efficacy of one 8 mg tablet ondansetron (OND), and in case of failure, to measure the recovering level by the administration of 8 mg i.v. OND. One tablet of OND was given before the first course. A complete or major control of emetic episodes (EE) (0-2 EE) over the 24 first hours was obtained in 55 patients (62%). A complete or major control of nausea (absent or mild) was obtained in 46 patients (52%). A success, defined as a complete or major control for EE and nausea during the first 5 days, was obtained in 36 patients (40%). These 36 patients were treated again with 8 mg oral OND at the second course, with a success level of 61% (22/36). Among the 53 patients unresponsive to the oral OND, 38 were treated by 8 mg i.v. OND at the second course. A complete or major control for EE and for nausea over the first 24 hours was obtained respectively in 11 patients (29%), and 11 patients (29%). No success was obtained. The 15 remaining patients, who had a very bad tolerance at the first course were excluded from the study and treated by OND-methylprednisolon, with only one success obtained. This study shows that the exclusive use of one 8 tablet OND is not sufficient in prevention of emesis induced by a FEC regimen, and that failures are only partially recovered by the i.v. route.

The aim of this paper is to compare ondansetron to other antiemetic products used in cancerology. Twenty randomised trials studying ondansetron, and published in international reviews, were analyzed and synthesized. The conclusion is that ondansetron is of demonstrated short term efficiency. It seems to be slightly more efficient than metoclopramide, and its association with dexamethasone increases its efficiency. Doses of 8 mg or 24 mg do not differ from doses of 32 mg, and bolus administration from infusion administration. There are no data on the duration of the protection after the first course of chemotherapy.

This study was carried out to assess the efficacy of oral ondansetron, a new 5HT3 receptor antagonist, in patients undergoing thyroid surgery. It included 60 patients, randomly assigned to two groups, and receiving orally, 1 h before induction of anaesthesia, either 8 mg of ondansetron (n = 29) or a placebo (n = 30). One patient was excluded. The same anaesthetic protocol, consisting of 3 to 5 micrograms.kg-1 of fentanyl, 4 to 6 mg.kg-1 of thiopentone, and 0.5 mg.kg-1 of atracurium, was used in all. Anaesthesia was maintained with 50% nitrous oxide in oxygen with 0.8 to 1% endtidal concentration of isoflurane and additional boluses of 0.1 mg of fentanyl as required. The incidence and intensity of nausea, graded mild, moderate or severe, and the incidence of vomiting were recorded postoperatively. During the first twelve hours after surgery, 40% of patients in the placebo group had nausea (16.7% mild, 20% moderate and 6.7% severe), and 50% vomited. In the ondansetron group, nausea and vomiting occurred in 13.8% and 20.4% of patients respectively. The 4 patients in the latter group complained of major nausea. The differences between the groups were statistically significant: p = 0.025 for nausea and p = 0.042 for vomiting. It is concluded that oral ondansetron, 8 mg taken orally 1 h before surgery, significantly reduces the incidence of nausea and vomiting during the first twelve postoperative hours. As it is easy to use and has no side-effects, it might be of interest in day-case surgery patients, despite its high cost.