米氮平预防大剂量顺铂化疗的恶心和呕吐的临床研究

A clinical study about Mirtazapine to prevent nausea and emesis caused by high-dose cisplatin-based chemotherapy

目的观察米氮平对大剂量顺铂化疗引起的恶心和呕吐的预防效果和安全性。方法采用自身交叉对照方法。63例大剂量顺铂（60 mg/m2或75 mg/m2）联合吉西他滨化疗者在第一周期时随机分配至对照（A）周期或米氮平（B）周期;第2周期用药互相交叉。A和B两周期化疗方案相同。d1~d5代表化疗周期的第1~5天。恶心、呕吐或食欲减退明显减少的患者比例用控制率表示;完全控制（complete response,CR）率代表无恶心、无呕吐或无食欲减退的比例。共观察d1~d5的恶心、呕吐、食欲减退的控制率。A周期采用恩丹西酮联合地塞米松二药预防恶心和呕吐;B周期在A周期用药基础上联合米氮平。药物用法：（1）恩丹西酮8 mg,iv,每天3次,于d1和d2给药;（2）地塞米松5 mg,iv,每天1次,于d1和d2给药;（3）米氮平15 mg,每天1次,于d1~d5睡前口服;（4）吉西他滨1000 mg/m2或1250 mg/m2,iv,于d1、8给药;（5）顺铂60 mg/m2或75 mg/m2,iv,分2天（于d1、d2）给药。结果米氮平（B）周期与A周期的恶心、急性呕吐、迟发性呕吐、食欲减退控制率分别为71.4%（45/63例）与65.1%（41/63例）（P〈0.01）、79.4%（50/63例）与68.3%（43/63例）（P〈0.01）、88.9%（56/63例）与61.9%（39/63例）（P〈0.01）、50.8%（32/63例）与25.4%（16/63例）（P〈0.05）。B与A周期的恶心、急性呕吐、迟发性呕吐、食欲减退控制率的CR率分别为52.4%（33/63例）与46.0%（29/63例）（P〉0.05）、74.6%（47/63例）与60.3%（38/63例）（P〈0.01）、49.2%（31/63例）与22.2%（19/63例）（P〈0.01）、47.6%（30/63例）与23.8%（15/63例）（P〈0.05）。B与A周期之间迟发性呕吐控制率差值明显高于急性呕吐控制率差值（27.0%vs.11.1%,P〈0.01）。B与A周期中均未见严重副作用。结论米氮平可有效控制大剂量顺铂化疗所致的恶心、呕吐和食欲减退;而迟发性呕吐改善相对更明显。

Objective To observe the effects and safety of Mirtazapine in prevention of nausea and emesis caused by high-dose cisplatin-based chemotherapy. Methods This was a self-controlled crossover clinical trial. Sixty-three patients, treated by high-dose cisplatin（60 mg/m2 or 75 mg/m2） plus gemcitabine, were randomly assigned to either control （A） cycle or Mirtazapine （B） cycle with first course, with crossover to the opposite treatment with the second course. The identical chemotherapy regimen was used on cycle A and cycle B. The dl-d5 served as first day through fifth day of chemotherapy cycle. The significant protection from nausea, emesis and anorexia was denoted as control rates, the complete protection rate denoted by CR rates. The control rates of nausea, emesis and anorexia on dl-d5 were observed. Patients received ondansetron with dexamethasone on cycle A to prevent nausea, emesis and anorexia. The mirtazapine in combination with ondansetron and dexamethasone was used on cycle B. Drug methods was used as following： Ondansetron 8 mg （intravenous, iv）, once daily on days 1 and 2 of chemotherapy, cisplatin 60 mg/m2 or 75 mg/m2, iv, used in two-day schedules, mirtazapine 15 mg orally once daily on days 1 through 5 of chemotherapy, dexamethasone 5 mg iv, once per day on days 1 and 2, and gemcitabine 1000 mg/m2 or 1250 mg/m2, iv, once daily on days 1 and days 8. Results The control rate of nausea, acute emesis, delayed emesis and anorexia on cycle B or A was 71.4%（45/63） or 65.1%（41 /63）（P〈0.01）, 79.4%（50/63） or 68.3%（43/63）（P〈0.01）, 88.9%（56/63） or 61.9%（39/63）（P〈0.01）, and 50.8%（32/63）（41/63） or 25.4%（16/63）（P〈0.05） of patients, respectively. The CR rate of nausea, acute emesis, delayed emesis and anorexia on cycle B or A was achieved in 52.4%（33/63） or 46.0%（29/63）（P 〉 0.05）, 74.6%（47/63） or 60.3%（38/63）（P〈：0.01）, 49.2%（31/63） or 22.2%（19/63）（P〈0.01）, and 47.6%（30/63） or 23.8%（15/63）（P〈0.05） of patients, respectively. More protection from delayed emesis was observed than from acute emesis （27.0% vs. 11.1%, P〈0.01）. No serious adverse events were observed on cycle B or A. Conclusion Mirtazapine is effective in treatment of nausea, emesis and anorexia caused by high dose cisplatin-based chemotherapy. Also, the improvement of delayed emesis is more obviously.