Zhou Michelle, Popovic Marko, Pasetka Mark, Pulenzas Natalie, Ahrari Soha, Chow Edward, DeAngelis Carlo
Department of Pharmacy, Odette Cancer Center, Sunnybrook Health Sciences Center, University of Toronto, Toronto, ON, Canada.
Ther Clin Risk Manag. 2015 May 5;11:713-29. doi: 10.2147/TCRM.S68130. eCollection 2015.
Nausea and vomiting are major adverse effects of chemotherapy and can greatly impact patients' quality of life. Although chemotherapy-induced nausea and vomiting (CINV) prevalence is high, treatment remains difficult. Palonosetron is a 5-hydroxytryptamine receptor antagonist (5-HT3RA) approved for treatment of CINV. The purpose of this review is to discuss existing and emerging therapeutic options, and examine studies focusing on palonosetron with regards to efficacy, pharmacology, tolerability, safety, and patient-derived outcomes.
A literature search was conducted using Ovid MEDLINE and EMBASE to identify relevant studies using palonosetron alone or in combination with other antiemetics. Studies were extracted if they included complete response (CR), complete control (CC), no nausea, no vomiting, and no rescue medications as an endpoint. Studies were also included if safety endpoints were examined.
Palonosetron alone has been shown to improve CR and CC rates for patients receiving low, moderate, or high emetogenic chemotherapy. Rates were further improved with the addition of dexamethasone, a corticosteroid. Furthermore, the addition of neurokinin-1 receptor antagonists, such as netupitant markedly improved efficacy profiles compared to palonosetron alone. Aprepitant is an antiemetic that has exhibited positive results in combination with palonosetron. Recently, a new drug consisting of netupitant and palonosetron (NEPA) has demonstrated significantly more efficacious prevention of CINV. Regardless of the combination, palonosetron has been well tolerated. The most common adverse events were constipation, headache, fatigue, and dizziness, with the majority of patients describing them as only mild or moderate.
Palonosetron, alone or with other antiemetics, has improved CINV treatment due to its ability to significantly reduce delayed phases of CINV, compared to similar 5-HT3RAs. Palonosetron is both more effective than first generation 5-HT3RAs and safer, as it results in a smaller prolongation of the QTc interval, compared to other 5-HT3RAs.
恶心和呕吐是化疗的主要不良反应，会极大影响患者的生活质量。尽管化疗引起的恶心和呕吐（CINV）发生率很高，但治疗仍然困难。帕洛诺司琼是一种被批准用于治疗CINV的5-羟色胺受体拮抗剂（5-HT3RA）。本综述的目的是讨论现有的和新出现的治疗选择，并研究聚焦于帕洛诺司琼在疗效、药理学、耐受性、安全性及患者相关结局方面的研究。
使用Ovid MEDLINE和EMBASE进行文献检索，以识别单独使用帕洛诺司琼或与其他止吐药联合使用的相关研究。如果研究将完全缓解（CR）、完全控制（CC）、无恶心、无呕吐及未使用解救药物作为终点，则纳入该研究。如果研究考察了安全性终点，也将其纳入。
已证明，单独使用帕洛诺司琼可提高接受低、中或高致吐性化疗患者的CR和CC率。添加皮质类固醇地塞米松后，这些比率进一步提高。此外，与单独使用帕洛诺司琼相比，添加神经激肽-1受体拮抗剂（如奈妥匹坦）可显著改善疗效。阿瑞匹坦是一种与帕洛诺司琼联合使用时显示出阳性结果的止吐药。最近，一种由奈妥匹坦和帕洛诺司琼组成的新药（NEPA）已证明对CINV的预防效果显著更佳。无论联合使用何种药物，帕洛诺司琼的耐受性都良好。最常见的不良事件为便秘、头痛、疲劳和头晕，大多数患者称这些症状仅为轻度或中度。
与类似的5-HT3RA相比，帕洛诺司琼单独使用或与其他止吐药联合使用时，由于其能够显著减少CINV的延迟期，因而改善了CINV的治疗。帕洛诺司琼比第一代5-HT3RA更有效且更安全，因为与其他5-HT3RA相比，它导致QTc间期延长的幅度更小。
