THE EFFICACY OF A COMBINATION OF ONDANSETRON, METHYLPREDNISOLONE AND METOPIMAZINE IN PATIENTS PREVIOUSLY UNCONTROLLED WITH A DUAL ANTIEMETIC TREATMENT IN CISPLATIN-BASED CHEMOTHERAPY

Background. Cisplatin is one of the most effective cytotoxic drugs use d in the treatment of certain neoplasms, but is also one which most fr equently induces nausea and vomiting. Combination of corticosteroids w ith ondansetron enables greater control of emesis than that obtained w ith ondansetron alone, but some patients still experience symptoms. Th e objective of this randomised, double-blind, multicentre, parallel gr oup study was to examine the benefit of the addition elf metopimazine (MPZ), a dopamine receptor antagonist, to the combination of ondansetr on + methylprednisolone (O + M) in the prevention of cisplatin-induced nausea and vomiting in patients uncontrolled [i.e., at least one emet ic episode (vomiting and/or retching) or moderate or severe nausea] du ring their previous course of cisplatin based chemotherapy, despite an tiemetic treatment with a combination of a 5-hydroxytryptamine(3) rece ptor antagonist (5HT(3)) with a corticosteroid. The impact of the trea tment on the patients' quality of life was also evaluated using two sp ecific 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 patien ts 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 g roup 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 D 2 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 chemother apy 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 methylprednisol one as above. Results. Analysis of the primary efficacy criterion (abs ence of emetic episode throughout the course of chemotherapy) revealed a success rate of 53% in the group receiving O + M + MPZ and 38% in t he group receiving O + M (P = 0.008). Analysis of the secondary effica cy criteria (nausea grade, number of emetic episodes and global patien t satisfaction on D1 and from D2 to D3) showed a statistically signifi cant difference between the two groups, in favour of the O + M + MPZ t reatment. The scores obtained with the FLIC and FLIE questionnaires di d not reveal any significant differences between the two groups. Treat ment was well tolerated in both groups. Conclusion: The study showed t hat the addition of MPZ to the combination O + M was an effective and well tolerated antiemetic treatment, with a 15% increase in efficacy c ompared to the combination in patients not controlled during their pre vious course of chemotherapy. The addition of metopimazine to existing regimens containing 5HT(3) receptor antagonist and steroid combinatio n should be considered for patients who fail on their previous course.