The efficacy of a combination of ondansetron, methylprednisolone and metopimazine in patients previously uncontrolled with a dual antiemetic treatment in cisplatin-based chemotherapy. The French Ondansetron Study Group.

BACKGROUND: Cisplatin is one of the most effective cytotoxic drugs used in the treatment of certain neoplasms, but is also one which most frequently induces nausea and vomiting. Combination of corticosteroids with ondansetron enables greater control of emesis than that obtained with ondansetron alone, but some patients still experience symptoms. The objective of this randomised, double-blind, multicentre, parallel group study was to examine the benefit of the addition of metopimazine (MPZ), a dopamine receptor antagonist, to the combination of ondansetron + methylprednisolone (O + M) in the prevention of cisplatin-induced nausea and vomiting in patients uncontrolled [i.e., at least one emetic episode (vomiting and/or retching) or moderate or severe nausea] during their previous course of cisplatin based chemotherapy, despite antiemetic treatment with a combination of a 5-hydroxytryptamine3 receptor antagonist (5HT3) with a corticosteroid. The impact of the treatment on the patients' quality of life was also evaluated using two specific questionnaires the FLIC (Functional Living Index for Cancer), and the FLIE (Functional Living Index for Emesis). PATIENTS AND METHODS: The intent-to-treat population consisted of 338 patients; 168 patients received the triple combination of ondansetron, methylprednisolone and metopimazine (O + M + MPZ), and 170 patients received ondansetron plus methylprednisolone (O + M). Tumour type was comparable in the two treatment groups, the most prevalent being lung cancer. Patients in group O + M + MPZ received ondansetron as an 8 mg intravenous injection prior to chemotherapy on day 1 followed by 8 mg tablets b.i.d. from D2 to D3, methylprednisolone as a 120 mg intravenous injection prior to chemotherapy on D1 and followed by 16 mg tablets b.i.d. from D2 to D3, and metopimazine as a 40 mg intravenous injection prior to chemotherapy on D1 and followed by 15 mg capsules b.i.d. on D2 to D3. Patients in group O + M received treatment with ondansetron and methylprednisolone as above. RESULTS: Analysis of the primary efficacy criterion (absence of emetic episode throughout the course of chemotherapy) revealed a success rate of 53% in the group receiving O + M + MPZ and 38% in the group receiving O + M (P = 0.008). Analysis of the secondary efficacy criteria (nausea grade, number of emetic episodes and global patient satisfaction on D1 and from D2 to D3) showed a statistically significant difference between the two groups, in favour of the O + M + MPZ treatment. The scores obtained with the FLIC and FLIE questionnaires did not reveal any significant differences between the two groups. Treatment was well tolerated in both groups. CONCLUSION: The study showed that the addition of MPZ to the combination O + M was an effective and well tolerated antiemetic treatment, with a 15% increase in efficacy compared to the combination in patients not controlled during their previous course of chemotherapy. The addition of metopimazine to existing regimens containing 5HT3 receptor antagonist and steroid combination should be considered for patients who fail on their previous course.

[Value of the combination of oral ondansetron with methylprednisolone as soon as the first cure in mild emetogenic chemotherapy. Groupe français d'étude de l'ondansétron]. / Intérêt de l'association ondansétron comprimé et méthylprednisolone dès la première cure dans les chimiothérapies moyennement émétisantes. Groupe français d'étude de l'ondansétron.

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.

Ondansetron suppository: an effective treatment for the prevention of emetic disorders induced by cisplatin-based chemotherapy. French Ondansetron Study Group.

This multicentre, randomised, double-blind, double-dummy, parallel group study was investigated in order to compare on 3 days the efficacy and the safety of the 16 mg once a day (od) ondansetron suppository (suppository group) with the recommended ondansetron treatment, i.e. 8 mg intravenous (i.v.) ondansetron on day 1 followed by 8 mg tablet (p.o.) twice daily (i.v. + p.o. group) on days 2 and 3 in patients receiving cisplatin (> or = 50 mg/m2) containing chemotherapy. In the 420 patients included in the intent-to-treat population, 209 received the 16 mg suppository and 211 the i.v. + p.o. treatment. The number of emetic episodes and the nausea score were recorded each day. Concerning the primary criterion, both treatments provided good anti-emetic control with 87% of all patients having a complete or major response (0-2 emetic episodes) on day 1 in the suppository group and 92% in the i.v. + p.o. group (P = 0.058). The 90% confidence interval for the difference between the two treatments for complete or major control was included in the interval (-15%, 15%) and showed that the treatment groups could be regarded as equivalent. Small differences in favour of the i.v. + p.o. group were observed concerning the secondary parameters. Both treatments were well tolerated. The results of this study show that both treatments are equivalent in the prevention of cisplatin-containing chemotherapy induced emesis for the primary efficacy criteria and that the ondansetron suppository is efficient and well tolerated and is a suitable alternative to the anti-emetic treatment combining the intravenous and oral routes.

A randomized study of ondansetron syrup in children: evaluation of taste acceptability and tolerance.

Ondansetron, a highly selective 5-HT3 receptor antagonist, is available in an intravenous (IV) formulation and tables, but syrup would be particularly useful in children. As chemotherapy can affect taste perceptions, this study was undertaken to determine the preference between two flavors of ondansetron syrup in children undergoing chemotherapy. Fifty-nine children, randomized into a multicenter, double-blind, crossover study, each received 5 mg/m2 of IV ondansetron daily before chemotherapy. The syrup was then randomly given in two doses, one of each flavor, strawberry and grape, 30 minutes apart. The preference was assessed 30 minutes after the second dose of syrup had been administered. Taste was assessed by the child against a panel of five faces. Of those children expressing any preference, 70% preferred the strawberry flavor. Overall, 59% of children preferred the strawberry flavor, whilst 25% preferred grape (P = 0.005) and 15% expressed no preference. The only adverse event assessed as drug related by the investigator was constipation, which occurred in one patient. In conclusion, a strong preference was found for the strawberry formulation. The ondansetron syrup was safe and well tolerated.

[Efficacy of ondansetron in radiation-induced nausea and vomiting: review of the literature]. / Efficacité de l'ondansétron dans les nausées et vomissements radio-induits: revue de la littérature.

Radiotherapy-induced emesis depends on the site of irradiation, the field size and the dose per fraction and is generally less intense than chemotherapy-induced emesis. Established anti-emetic drugs offer only limited symptom control (50%). Ondansetron, a 5HT3 receptors antagonist, had proven a complete or a major control efficacy (0-2 emetic episodes) of 68 to 95% in three pilot studies (fractionated, single-dose and total body irradiations). In controlled studies, ondansetron efficacy was significantly higher than placebo, metoclopramide and prochlorperazine. The treatment was well tolerated in the different studies.