Celio Luigi, Niger Monica, Ricchini Francesca, Agustoni Francesco
Medical Oncology Unit 1, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Core Evid. 2015 Aug 21;10:75-87. doi: 10.2147/CE.S65555. eCollection 2015.
The second-generation 5-hydroxytryptamine-3 (5-HT3) receptor antagonist palonosetron is effective in the prevention of chemotherapy-induced nausea and vomiting (CINV) associated with highly and moderately emetogenic chemotherapy (HEC and MEC, respectively). In addition, palonosetron has been the first and, at present, the only 5-HT3 receptor antagonist to have a specific indication for the prevention of delayed CINV associated with MEC. The unique pharmacology of this antagonist is thought to partly explain its improved efficacy against delayed symptoms.
To review the evidence underlying the use of palonosetron in preventing CINV.
A recent meta-analysis consistently showed that palonosetron significantly increases the control of both emesis and nausea during the acute and delayed phases after single-day HEC or MEC. Consistent with these findings from trials that did not include an neurokinin-1 (NK-1) receptor antagonist, randomized controlled trials recently showed that a triple combination with palonosetron achieves significantly better control of delayed CINV, particularly delayed nausea, in patients undergoing HEC or the high-risk combination of an anthracycline and cyclophosphamide (AC). Evidence from randomized studies also supports palonosetron as a valuable option to reduce the total corticosteroid dose administered in patients undergoing multiple cycles of MEC or AC chemotherapy. Additional benefits of palonosetron include the lack of a warning on cardiac safety and no known clinically significant drug-drug interactions. Place in therapy and conclusion: Evidence currently available indicates that palonosetron significantly adds to the clinician's ability to effectively control CINV in patients undergoing HEC or MEC. It is recommended in the international guidelines for the prevention of CINV caused by MEC. The high safety profile and the opportunity to reduce the total corticosteroid dose with no loss in efficacy against delayed CINV should also contribute to a wider use of palonosetron in clinical practice.
第二代5-羟色胺-3(5-HT3)受体拮抗剂帕洛诺司琼可有效预防与高致吐性化疗和中度致吐性化疗(分别为HEC和MEC)相关的化疗引起的恶心和呕吐(CINV)。此外,帕洛诺司琼是首个且目前唯一一种有预防与MEC相关的迟发性CINV特定适应症的5-HT3受体拮抗剂。这种拮抗剂独特的药理学特性被认为部分解释了其对迟发性症状疗效更佳的原因。
综述帕洛诺司琼用于预防CINV的证据。
最近一项荟萃分析一致表明,帕洛诺司琼能显著提高单日HEC或MEC后急性期和延迟期呕吐和恶心的控制率。与这些未纳入神经激肽-1(NK-1)受体拮抗剂的试验结果一致,近期的随机对照试验表明,在接受HEC或蒽环类药物与环磷酰胺(AC)高风险联合化疗的患者中,帕洛诺司琼三联疗法能显著更好地控制迟发性CINV,尤其是迟发性恶心。随机研究的证据也支持帕洛诺司琼作为一种有价值的选择,可减少接受多个周期MEC或AC化疗患者的总皮质类固醇剂量。帕洛诺司琼的其他益处包括没有心脏安全性警告且无已知临床显著的药物相互作用。治疗地位与结论:现有证据表明,帕洛诺司琼显著增强了临床医生有效控制接受HEC或MEC患者CINV的能力。它被推荐用于预防MEC所致CINV的国际指南中。其高安全性以及在不降低对迟发性CINV疗效的情况下有机会减少总皮质类固醇剂量,也应有助于帕洛诺司琼在临床实践中更广泛地应用。