Stewart A, McQuade B, Cronje J D, Goedhals L, Gudgeon A, Corette L, Froger X, Tubiana-Hulin M, Laplaige P, Roberts J T
Christie Hospital, Manchester, UK.
Oncology. 1995 May-Jun;52(3):202-10. doi: 10.1159/000227458.
This is the first double-blind clinical trial in a homogenous group of patients to compare the recommended dosing schedules of ondansetron and granisetron in the control of prolonged emesis after cyclophosphamide-containing chemotherapy (48% CMF, 35% EC) for breast cancer. A total of 514 patients were recruited. Of the 488 patients included in the intent-to-treat analyses, 167 were randomised to group A [8 mg ondansetron intravenously (i.v.) + placebo by mouth (p.o.) before chemotherapy + 8 mg ondansetron p.o. twice daily (b.d.) until day 5], 155 to group B (placebo i,.v. + 8 mg ondansetron p.o. before chemotherapy + 8 mg ondansetron p.o. b.d. until day 5) and 166 to group C (3 mg granisetron i.v. + placebo p.o. before chemotherapy + placebo p.o. b.d. until day 5). On study day 1, the groups were comparable with respect to the proportion of patients experiencing up to 2 emetic episodes (group A: 89%; B: 86%; C: 91%) and in the severity of nausea (no nausea; group A: 51%; B: 55%; C: 54%). Over the 5-day study period significantly more patients were rescued or withdrawn due to lack of response after the granisetron regimen (26%) than after the i.v. + p.o. ondansetron regimen (11%; p < 0.001). Since there was no difference in these parameters on day 1, this reflects differences on days 2-5 and was also reflected in the all-oral ondansetron group over this period (group B: 12%; C: 22% on days 2-5). A significant difference in the severity of nausea after i.v. and p.o. ondansetron compared with granisetron was also observed over the 5-day study period (p = 0.009). This was reflected in a numerical difference in favour of the all-p.o. ondansetron regimen compared with the granisetron regimen (no nausea; group A: 33%; B: 34%; C: 25%). Again these differences reflected differences in nausea control on days 2-5, since no differences were observed on day 1. Logistic regression analyses adjusted for prognostic factors also revealed a significant difference (p = 0.011) in favour of the i.v. + ondansetron group compared with the granisetron group when complete plus major response was compared over days 2-5. No significant differences in the safety profiles of the three treatment groups were observed. There were no severe or unexpected drug-related adverse events and as is well established for the serotonin receptor antagonists, mild constipation (mean 8%) and mild headache (mean 8%) were most commonly reported.
这是在一组同质患者中进行的第一项双盲临床试验，旨在比较昂丹司琼和格拉司琼在控制含环磷酰胺的乳腺癌化疗（48%CMF，35%EC）后长期呕吐时的推荐给药方案。共招募了514名患者。在纳入意向性分析的488名患者中，167名被随机分配到A组[化疗前静脉注射（i.v.）8mg昂丹司琼+口服（p.o.）安慰剂+化疗后每日两次口服8mg昂丹司琼，直至第5天]，155名被分配到B组（静脉注射安慰剂+化疗前口服8mg昂丹司琼+化疗后每日两次口服8mg昂丹司琼，直至第5天），166名被分配到C组（化疗前静脉注射3mg格拉司琼+口服安慰剂+化疗后每日两次口服安慰剂，直至第5天）。在研究第1天，三组在经历最多2次呕吐发作的患者比例方面具有可比性（A组：89%；B组：86%；C组：91%），在恶心严重程度方面也具有可比性（无恶心；A组：51%；B组：55%；C组：54%）。在为期5天的研究期间，由于格拉司琼治疗方案后无反应而需要抢救或退出研究的患者显著多于静脉注射+口服昂丹司琼治疗方案后（26%比11%；p<0.001）。由于这些参数在第1天没有差异，这反映了第2 - 5天的差异，并且在此期间全口服昂丹司琼组也有体现（B组：第2 - 5天为12%；C组：第2 - 5天为22%）。在为期5天的研究期间，还观察到静脉注射和口服昂丹司琼后恶心严重程度与格拉司琼相比有显著差异（p = 0.009）。这表现为全口服昂丹司琼治疗方案与格拉司琼治疗方案相比在无恶心方面存在数值差异（A组：33%；B组：34%；C组：25%）。同样，这些差异反映了第2 - 5天在恶心控制方面的差异，因为在第1天未观察到差异。对预后因素进行调整的逻辑回归分析还显示，如果在第2 - 5天比较完全缓解加主要缓解情况，与格拉司琼组相比，静脉注射+昂丹司琼组具有显著差异（p = 0.011）。在三个治疗组的安全性方面未观察到显著差异。没有严重或意外的药物相关不良事件，并且正如5 - 羟色胺受体拮抗剂所熟知的那样，最常报告的是轻度便秘（平均8%）和轻度头痛（平均8%）。
