奥氮平可对抗化疗引起的恶心呕吐

即将在芝加哥召开的美国临床肿瘤学会(ASCO)年会会前新闻会上报告的一项临床试验表明，抗精神病药物奥氮平治疗突破性化疗引起的恶心呕吐(CINV)优于标准治疗药物胃复安，该结果将有望改变某些癌症患者治疗方案。

在这项双盲III期试验中，印第安纳大学哈珀癌症研究所所长Rudolph M. Navari博士及其同事招募了接受高致吐性化疗药物(顺铂>70 mg/m²、阿霉素>50 mg/m²或环磷酰胺>600 mg/m²)的初始化疗患者。按照治疗指南接受预防用药但仍出现突破性恶心呕吐的患者随机服用奥氮平(再普乐，10 mg/d，3d)或胃复安(10 mg，3次/d，3d)。化疗前预防用药包括地塞米松(12 mg，IV)、帕洛诺司琼(0.25 mg，IV)和福沙吡坦(150 mg，IV)，化疗后预防用药为地塞米松(8 mg/d，2~4d，p.o.)。监测患者服药后72 h恶心呕吐情况，并应用视觉模拟量表评估患者恶心程度(0~10分，0分为无恶心，10分为最严重恶心)。两组患者年龄、性别、东部肿瘤协作组(ECOG)功能状态以及确诊情况(5例膀胱癌、40例乳腺癌、8例淋巴瘤和27例肺癌)均相似。

结果显示，在72 h观察期内，奥氮平组和胃复安组分别有71%(30/42例)和32%(12/38例)患者未出现呕吐(P<0.01)，未出现恶心的患者比例分别为67%(28/42例)和24% (9/38例)(P<0.01)。奥氮平和胃复安均呈现良好的耐受性，未见3或4级毒性，也均未见中枢神经系统毒性。奥氮平作为抗精神病药物，患者服用3、6及9个月时出现体重增加的副作用，但在本研究中患者每月用药为3～4 d，未见该副作用，研究者在既往研究中也未见该副作用。

研究者此前曾报告，在一项III期临床试验中，接受高致吐性化疗药物治疗患者服用奥氮平后未出现任何迟发性恶心的几率约是服用标准止吐药物阿瑞吡坦(Emend)患者的2倍(68% vs. 37%)。两种方案预防急性恶心、急性和迟发性呕吐均具有良好效果(Support. Oncol. 2011;9:188-95)。

会议主持人、ASCO候任主席、华盛顿医学中心癌症研究所的Sandra M. Swain博士指出：“为治愈这些患者，我们走过了漫长的道路，但这些副作用使患者无法耐受，有时不得不放弃治疗。该研究结果为改善患者生活质量迈出了重要一步，可望改善上述局面。”

 ASCO网站(www.asco.org)已在线刊登了许多会议报告摘要，提前展示了会议精彩内容。

The antipsychotic olanzapine trounced standard therapy for breakthrough chemotherapy-induced nausea and vomiting in a clinical trial that could change the way some cancer patients are treated.

In the double-blind phase III study, 30 (71%) of 42 patients, who received olanzapine (Zyprexa) had no emesis, compared with 12 (32%) of 38 patients who received metoclopramide (P less than .01) during a 72-hour observation period after highly emetic chemotherapy.

In addition, 28 (67%) patients on olanzapine had no nausea, compared with 9 (24%) of those patients on metoclopramide (P less than .01), said Dr. Rudolph M. Navari, who presented the study during a press briefing in advance of the annual meeting of American Society of Clinical Oncology, June 1-5, in Chicago. Dr. Navari is the director of the Harper Cancer Institute at Indiana University in South Bend.

ASCO president-elect Dr. Sandra M. Swain, medical director of the Cancer Institute at Washington Hospital Center, called the findings “a great step forward for quality of life for our patients.

“This is a huge advance,” said Dr. Swain, a breast cancer expert, who comoderated the teleconference. “We’ve come a long way to really treat and cure these patients ... these side effects can be intolerable to patients. Sometimes patients will opt out of curative treatment, and we certainly don’t want that, when we know we’ve made advances.”

The researchers included chemotherapy-naive patients who received highly emetogenic chemotherapy: more than 70 mg/m² cisplatin, or more than 50 mg/m² doxorubicin and more than 600 mg/m² cyclophosphamide.

Patients who developed breakthrough emesis or nausea despite guideline-directed prophylaxis were randomized to receive olanzapine or metoclopramide. Pre-chemotherapy prophylaxis included intravenous dexamethasone (12 mg), intravenous palonosetron (0.25 mg), and intravenous fosaprepitant (150 mg); post-chemotherapy prophylaxis was daily oral dexamethasone (8 mg, days 2-4).

Patients received 10 mg oral olanzapine for 3 days or 10 mg oral metoclopramide three times daily for 3 days. Patients were monitored for emesis and nausea for the 72 hours after the initiation of therapy. In addition, nausea was measured by patients on a visual analog scale (0-10), with 0 being no nausea and 10 being maximal nausea.

Patients in the two groups were similar for age, sex, Eastern Cooperative Oncology Group (ECOG) performance status, and diagnosis (5 bladder cancers, 40 breast cancers, 8 lymphomas, and 27 lung cancers).

“Both olanzapine and metoclopramide were well tolerated with no grade 3 or 4 toxicities,” said Dr. Navari. No central nervous system toxicities were observed in either group.

Olanzapine is indicated for treatment of psychosis and is associated with weight gain, but the side effect should not be a problem for cancer patients.

“The side effect of weight gain occurs in patients, who receive the drug for 3 to 6 to 9 months,” Dr. Ravari noted. “So using it for a short period of 3-4 days once a month – we did not see that in the current study, nor did we see that in previous studies.”

Dr. Navari had previously reported that patients receiving highly emetogenic chemotherapy were about twice as likely not to experience any delayed nausea with an olanzapine regimen compared with a standard aprepitant (Emend) regimen (68% vs. 37%) in a phase III clinical trial. The two regimens worked similarly well for preventing acute nausea and for preventing both acute and delayed vomiting, that study found (Support. Oncol. 2011;9:188-95).

ASCO presented a preview of some meeting highlights with many of the abstracts being posted online as of 6 p.m. EST at www.asco.org.

The authors reported that they have nothing to disclose.