O'Brien M E, Cullen M H, Woodroffe C, Kelly K, Burman C, Palmer K, Stuart N S, Blackledge G R, Sharpe J
Cancer Research Campaign, Clinical Trials Unit, Queen Elizabeth Hospital, Birmingham, UK.
Br J Cancer. 1989 Nov;60(5):759-63. doi: 10.1038/bjc.1989.354.
High dose metoclopramide is an effective anti-emetic for use with cisplatin containing chemotherapy regimens but can cause extrapyramidal reactions. Lorazepam and dexamethasone are increasingly being used to alleviate chemotherapy induced emesis. This trial has assessed the contribution of high dose metoclopramide to anti-emetic control when given with dexamethasone and lorazepam. Eight-one patients receiving chemotherapy, mainly for gynaecological malignancy, entered a randomised double blind cross-over trial comparing dexamethasone and lorazepam with or without a 24 h metoclopramide infusion. This was followed by oral dexamethasone with or without oral metoclopramide for three further days depending on the initial randomisation. Sixty-one patients were fully evaluable. Fifty-five received cisplatin containing regimens and six non-cisplatin regimens. There was a significant reduction in the number of episodes of vomiting during the first 24 h in patients receiving the metoclopramide combination (P = 0.0001). On first exposure to chemotherapy 45% of patients receiving dexamethasone, lorazepam and high dose metoclopramide had no vomiting while 67% had two episodes or less ('major control'). This compared to 11% total control and 25% major control in those receiving dexamethasone, lorazepam and placebo. The control of nausea in the first 24 h was also improved (P = 0.0001). There was no difference in the degree of nausea or vomiting during the following three weeks between those receiving oral dexamethasone alone and those receiving dexamethasone and metoclopramide. Both groups showed a significant increase in nausea in the three weeks following the second course of treatment when compared to the first (P = 0.0007). Extrapyramidal reactions were recorded in 11.5% of patients receiving metoclopramide. More patients stated a preference for the metoclopramide combination although this was not statistically significant (chi 2(1) = 0.29, P = 0.59). In conclusion the combination of dexamethasone and lorazepam can give major control of emesis in 25% of patients receiving very emetogenic chemotherapy. The addition of metoclopramide increases this to 67% on first exposure to chemotherapy, but at the expense of extrapyramidal reactions in 11.5%.
高剂量甲氧氯普胺是一种有效的止吐药，可用于含顺铂的化疗方案，但可能会引起锥体外系反应。劳拉西泮和地塞米松越来越多地用于缓解化疗引起的呕吐。本试验评估了高剂量甲氧氯普胺与地塞米松和劳拉西泮联用时在控制呕吐方面的作用。81例接受化疗（主要针对妇科恶性肿瘤）的患者进入了一项随机双盲交叉试验，比较了地塞米松和劳拉西泮加或不加24小时甲氧氯普胺输注的情况。随后根据初始随机分组情况，给予口服地塞米松加或不加口服甲氧氯普胺，持续三天。61例患者可进行全面评估。55例接受含顺铂方案，6例接受非顺铂方案。接受甲氧氯普胺联合用药的患者在最初24小时内呕吐发作次数显著减少（P = 0.0001）。首次接受化疗时，接受地塞米松、劳拉西泮和高剂量甲氧氯普胺的患者中，45%没有呕吐，67%呕吐发作两次或更少（“主要控制”）。相比之下，接受地塞米松、劳拉西泮和安慰剂的患者中，完全控制率为11%，主要控制率为25%。最初24小时内恶心的控制情况也有所改善（P = 0.0001）。在接下来的三周内，单独接受口服地塞米松的患者与接受地塞米松和甲氧氯普胺的患者在恶心或呕吐程度上没有差异。与第一个疗程相比，两组在第二个疗程后的三周内恶心均显著增加（P = 0.0007）。接受甲氧氯普胺的患者中有11.5%出现锥体外系反应。更多患者表示更喜欢甲氧氯普胺联合用药，尽管这在统计学上不显著（卡方检验(1)=0.29，P = 0.59）。总之，地塞米松和劳拉西泮联合用药可使25%接受高度致吐性化疗的患者实现呕吐的主要控制。在首次接受化疗时，加用甲氧氯普胺可将这一比例提高到67%，但代价是11.5%的患者出现锥体外系反应。
