Lebeau B, Depierre A, Giovannini M, Rivière A, Kaluzinski L, Votan B, Hédouin M, d'Allens H
Hôpital Saint-Antoine, Paris, France.
Ann Oncol. 1997 Sep;8(9):887-92. doi: 10.1023/a:1008276412559.
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).
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.
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.
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.
顺铂是治疗某些肿瘤最有效的细胞毒性药物之一，但也是最常引起恶心和呕吐的药物之一。皮质类固醇与昂丹司琼联合使用比单独使用昂丹司琼能更好地控制呕吐，但仍有一些患者会出现症状。这项随机、双盲、多中心、平行组研究的目的是检验在昂丹司琼 + 甲泼尼龙（O + M）联合用药基础上加用多巴胺受体拮抗剂甲氧氯普胺（MPZ），对既往接受基于顺铂的化疗过程中尽管使用了5-羟色胺3受体拮抗剂（5HT3）与皮质类固醇联合进行止吐治疗但仍未得到控制（即至少有一次呕吐发作（呕吐和/或干呕）或中度或重度恶心）的患者预防顺铂引起的恶心和呕吐的益处。还使用两份特定问卷，即癌症功能生活指数（FLIC）和呕吐功能生活指数（FLIE）评估了该治疗对患者生活质量的影响。
意向性治疗人群包括338例患者；168例患者接受昂丹司琼、甲泼尼龙和甲氧氯普胺三联组合（O + M + MPZ），170例患者接受昂丹司琼加甲泼尼龙（O + M）。两个治疗组的肿瘤类型具有可比性，最常见的是肺癌。O + M + MPZ组患者在第1天化疗前接受8 mg昂丹司琼静脉注射，随后从第2天至第3天每日两次口服8 mg片剂；在第1天化疗前接受120 mg甲泼尼龙静脉注射，随后从第2天至第3天每日两次口服16 mg片剂；在第1天化疗前接受40 mg甲氧氯普胺静脉注射，随后从第2天至第3天每日两次口服15 mg胶囊。O + M组患者接受上述昂丹司琼和甲泼尼龙治疗。
对主要疗效标准（化疗全过程无呕吐发作）的分析显示，接受O + M + MPZ组的成功率为53%，接受O + M组的成功率为38%（P = 0.008）。对次要疗效标准（恶心程度、呕吐发作次数以及第1天和第2天至第3天患者总体满意度）的分析显示，两组之间存在统计学显著差异，但更有利于O + M + MPZ治疗。FLIC和FLIE问卷获得的分数未显示两组之间有任何显著差异。两组对治疗的耐受性均良好。
该研究表明，在O + M联合用药基础上加用MPZ是一种有效且耐受性良好的止吐治疗方法，与既往化疗过程中未得到控制的患者使用的联合用药相比，疗效提高了15%。对于既往治疗失败的患者，应考虑在现有含5HT3受体拮抗剂和类固醇联合用药方案中加用甲氧氯普胺。
