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).


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.


CONCLUSIONS
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.
Lebeau
B
B
Hôpital Saint-Antoine, Paris, France.
Depierre
A
A
Giovannini
M
M
Rivière
A
A
Kaluzinski
L
L
Votan
B
B
Hédouin
M
M
d'Allens
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D007540:Isonipecotic Acids / Q000008:administration & dosage; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D009325:Nausea / Q000517:prevention & control*; D009369:Neoplasms / Q000188:drug therapy* / Q000523:psychology; D017294:Ondansetron / Q000008:administration & dosage; D011379:Prognosis; D011788:Quality of Life; D014839:Vomiting / Q000517:prevention & control*
D000932:Antiemetics; D000970:Antineoplastic Agents; D007540:Isonipecotic Acids; C005260:metopimazine; D017294:Ondansetron; D002945:Cisplatin; D008775:Methylprednisolone