编者按：在癌症治疗的征途中，化疗作为一把双刃剑，既为患者带来了生存的希望，也伴随着一系列不良反应，其中化疗所致的难治性恶心治疗起来尤为棘手。在第47届SABCS大会上，美国纽约罗切斯特大学医学癌症中心Luke Peppone教授为我们介绍了URCC 16070研究的结果（摘要号：RF2-06），这项全国性、双盲的III期随机对照试验，聚焦于奥氮平和丙氯拉嗪在治疗化疗所致难治性恶心中的疗效对比。肿瘤瞭望特邀Luke Peppone教授详细阐述了研究的初衷与设计，还深入分析了研究结果及其临床意义。他指出，尽管现有药物在控制呕吐方面表现优异，但恶心的控制仍需进一步优化。通过这项研究，我们有望为临床医生提供新的治疗选择，从而改善患者的生活质量。

Luke Peppone教授：许多接受化疗的乳腺癌患者都有恶心和呕吐的经历。我们目前使用的药物在控制呕吐方面非常有效，能够减少90%以上的呕吐。然而，对于恶心的控制效果则相对较差，改善幅度约为50%。这是因为恶心是一个更为复杂的症状，呕吐集中在大脑的一个特定区域，而恶心则涉及多个区域。因此，尽管呕吐得到了有效控制，患者仍然会感到恶心，这种不适感显然非常困扰患者。我们有两种药物，在美国早已获批，且我们对它们的使用经验丰富。我们了解它们的安全性，药物本身也相对安全，而且对于患者群体来说，价格较为亲民，供应也很充足，市场上有大量仿制药可供选择。因此，这些药物非常容易获得，这也是我们进行这项研究的一个重要原因。

 

 

Oncology Frontier:Could you tell us about the original intention of conducting this URCC 16070 phase III randomized controlled trial?Why choose olanzapine and prochlorperazine as agents for nausea caused by refractory chemotherapy?

 

Prof.Luke Peppone:So yeah，a lot of breast cancer patients undergoing chemotherapy will have nausea and vomiting.The drugs that we provide now are excellent at controlling vomiting with over 90%reduction.However，the control of nausea is less than that，around 50%.And that’s because it’s just a harder target for pharmaceuticals to hit，where vomiting is really one center in the brain，nausea is spread to a bunch.So they still have nausea despite a reduction in vomiting，which is quite unpleasant，as you can imagine.So we had two drugs，which were approved in the United States many，many years ago.And we have significant experience with these drugs.So we know their safety profile，they are definitely relatively safe，in terms of pharmaceuticals.And they are relatively cheap for our population and plentiful.They’re available and generic.So it’s very easy to get that.And that was sort of reason why we did this study.

 

Luke Peppone教授：这确实是个很好的问题。我们的研究结果显示，奥氮平（olanzapine）在缓解恶心方面略优于丙氯拉嗪（prochlorperazine），而且奥氮平还改善了患者的生活质量，而丙氯拉嗪则没有显现出类似的效果。这个问题并没有简单的答案，最终还需要临床医生根据患者的具体情况来做出判断。我认为，奥氮平可能是更好的选择，但丙氯拉嗪也是一个可行的替代方案。如果患者在使用奥氮平时出现过度镇静的副作用，可能需要考虑换成丙氯拉嗪，反之亦然。总的来说，这两种药物都是应对化疗引起的顽固性恶心的有效选择，奥氮平可能稍微更好，甚至可以作为首选，但最终的决定还是要根据每位患者的具体情况由临床医生来做出。

 

 

Oncology Frontier:According to the results of the study，olanzapine was significantly superior to placebo in reducing nausea and improving quality of life，but did not show superiority over prochlorperazine.How do you interpret this result?Does this mean that olanzapine is more appropriate as the first choice for the treatment of refractory chemotherapy-induced nausea?

 

Prof.Luke Peppone:Yeah，that’s a great question.Our results did show that olanzapine reduced nausea slightly more than prochlorperazine.And also，olanzapine resulted in an improvement of quality of life，where prochlorperazine did not.So it’s a tough question，but it’s a question that clinicians would have to answer for themselves.I would say olanzapine is probably the best choice.But I would also say that prochlorperazine is also a good choice.You might find that a patient is too sedated on olanzapine，so they might want to try prochlorperazine or vice versa.I think they’re both very good options for refractory nausea and chemotherapy patients，with olanzapine potentially being a slightly better choice and perhaps the first choice，but up to each clinician.

 

Luke Peppone教授：在安全性方面，这两种药物的表现都非常好，研究中没有出现与奥氮平或丙氯拉嗪相关的严重不良事件。我们确实观察到了一些不良反应，但这些都是预期中的情况。奥氮平已知会引起镇静和嗜睡，这也是我们在研究中遇到的常见不良反应，丙氯拉嗪也类似，但没有出现任何意料之外的副作用。对照组和研究组的药物干预之间的不良事件发生率相似。我们还在进一步分析这些数据，但总体来说，奥氮平和丙氯拉嗪在本研究以及以往的研究中的安全性都非常好，这也是我们选择这两种药物的众多原因之一，我们也很乐意在这些患者中使用它们。

 

Oncology Frontier:What was the safety profile of olanzapine and prochlorperazine in this study?Did any patients have serious adverse effects or need to discontinue the drug?What patient factors do you think need to be considered to ensure safety and tolerability when selecting this class of drugs?

 

Prof.Luke Peppone:So in terms of safety profile，both of those drugs were excellent，and we had no serious adverse events related to the study intervention drugs，either olanzapine or prochlorperazine.We had a number of adverse events that were all expected.Olanzapine is known to cause sedation and some drowsiness，and those were the typical adverse events that we dealt with，similar with prochlorperazine，but nothing unexpected.And adverse events between the placebo and the study interventions were very similar.We’re still teasing apart those，but the safety profile of those two drugs in our study and in previous research are excellent，and that’s one of the many reasons why they were chosen，and we like using these drugs in these patients.

 

Luke Peppone教授：我本人是医学博士，并不直接进行临床治疗。不过，我有许多非常亲近的同事，他们负责患者治疗。我们所在的罗切斯特大学癌症中心在化疗引起的恶心和呕吐领域有着长期的积累，多年来我们一直使用丙氯拉嗪来控制顽固性恶心。根据这项研究的结果，越来越多的临床医生开始转向使用奥氮平，而且取得了良好的效果。患者反映恶心症状显著减轻，这表明我们的临床实践正在发生积极变化，希望这种变化能够惠及更广泛的患者群体。

 

Oncology Frontier:Based on the results of this study，how would you personalize your antiemetic regimen in your clinical practice?How will the results of this study affect your clinical practice decisions?

 

Prof.Luke Peppone:Yeah，so I myself am a PhD，and I really don’t treat patients.However，I have a number of very close colleagues that treat their patients.Our university at the University of Rochester Medical Center has a long history in the nausea and vomiting realm due to chemotherapy，and we have used prochlorperazine for many years to control refractory nausea，and I will say in light of this study，more of our clinicians are moving towards olanzapine，and they’re having good results.Patients are saying that they are having significant reductions in nausea，so you can see that our clinical practice has slowly started changing where we are，and hopefully this trickles out to the rest of the population.

 

Luke Peppone

纽约罗切斯特大学医学癌症中心副教授