Celio Luigi, Agustoni Francesco, Testa Isabella, Dotti Katia, de Braud Filippo
Medical Oncology Unit 1, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Tumori. 2012 May-Jun;98(3):279-86. doi: 10.1177/030089161209800301.
In 2003, the second-generation, 5-HT(3) receptor antagonist (5-HT(3) RA) palonosetron was approved by the FDA for the prevention of nausea and vomiting associated with highly and moderately emetogenic chemotherapy. We reviewed the current knowledge on the role of palonosetron against acute and delayed emesis in patients with solid tumors undergoing single-day moderately emetogenic chemotherapy regimens.
A literature review in PubMed was performed to update currently available preclinical and clinical evidence on palonosetron, prioritizing randomized clinical trials.
The distinct pharmacology of palonosetron provides a rationale behind the improved efficacy observed with the drug in prevention of delayed symptoms. This may be explained by allosteric binding properties and by palonosetron-triggered receptor internalization, which result in prolonged inhibition of the 5-HT(3) receptor function. Very recent pharmacology experiments have also suggested that palonosetron would be able to differentially inhibit 5-HT(3)/neurokinin 1 (NK-1) receptor signaling cross-talk. In two recent meta-analyses, palonosetron was shown to be more effective than other available 5-HT(3) RAs in preventing acute and delayed nausea and vomiting for both HEC and MEC. Recent findings also suggest that a single-day regimen of palonosetron plus dexamethasone (both drugs administered intravenously) may provide a reasonable therapeutic alternative to reduce the total dexamethasone dose administered in patients undergoing moderately emetogenic chemotherapy.
On the basis of accumulating data, the evidence-based international guidelines devised from the major organizations have been recently updated to recommend the use of palonosetron plus 3-day dexamethasone for the optimal prevention of nausea and vomiting due to moderately emetogenic chemotherapy. There is still a need to investigate the efficacy of palonosetron in combination with an NK-1 receptor antagonist and dexamethasone in well-designed randomized trials.
2003年，第二代5-羟色胺3（5-HT(3)）受体拮抗剂帕洛诺司琼被美国食品药品监督管理局（FDA）批准用于预防与高度和中度致吐性化疗相关的恶心和呕吐。我们回顾了目前关于帕洛诺司琼在接受单日中度致吐性化疗方案的实体瘤患者中对抗急性和迟发性呕吐作用的相关知识。
在PubMed上进行文献综述，以更新目前关于帕洛诺司琼的临床前和临床证据，重点关注随机临床试验。
帕洛诺司琼独特的药理学特性为该药物在预防迟发性症状方面观察到的疗效改善提供了理论依据。这可能是由变构结合特性以及帕洛诺司琼引发的受体内化所解释的，这导致5-HT(3)受体功能的长期抑制。最近的药理学实验还表明，帕洛诺司琼能够差异性地抑制5-HT(3)/神经激肽1（NK-1）受体信号转导的相互作用。在最近的两项荟萃分析中，帕洛诺司琼在预防高度致吐性化疗（HEC）和中度致吐性化疗（MEC）的急性和迟发性恶心和呕吐方面比其他可用的5-HT(3)受体拮抗剂更有效。最近的研究结果还表明，帕洛诺司琼加地塞米松（两种药物均静脉给药）的单日方案可能为减少接受中度致吐性化疗患者的地塞米松总给药剂量提供一种合理的治疗选择。
基于积累的数据，主要组织制定的循证国际指南最近已更新，推荐使用帕洛诺司琼加3天地塞米松以最佳预防中度致吐性化疗引起的恶心和呕吐。仍有必要在精心设计的随机试验中研究帕洛诺司琼与NK-1受体拮抗剂和地塞米松联合使用的疗效。
