Center for Cancer and Blood Disorders, Bethesda, MD 20817, USA.
Support Care Cancer. 2013 May;21(5):1453-60. doi: 10.1007/s00520-012-1691-5. Epub 2013 Jan 26.
Palonosetron (Aloxi(®), Onicit(®)) is a pharmacologically unique 5-HT3 receptor antagonist (RA) approved as a single IV injection for the prevention of nausea and vomiting induced by chemotherapy (CINV) of either moderate or highly emetogenic potential (MEC and HEC, respectively). An oral palonosetron formulation has been developed and compared to the IV formulation.
In this multinational, multicenter, double-blind, double-dummy, dose-ranging trial, 651 patients were randomly assigned to receive one of the following as a single dose prior to moderately emetogenic chemotherapy: oral palonosetron 0.25, 0.50, and 0.75 mg or IV palonosetron 0.25 mg. Patients were also randomized (1:1) to receive dexamethasone 8 mg IV or matched placebo on day 1. The primary endpoint was complete response (CR; no emesis, no rescue therapy) during the acute phase (0-24 h).
Acute CR rates were 73.5, 76.3, 74.1, and 70.4 % for all patients receiving the palonosetron 0.25, 0.50, and 0.75 mg oral doses, and for IV palonosetron 0.25 mg, respectively; delayed CR (24-120 h) rates were 59.4, 62.5, 60.1, and 65.4 %, and overall CR (0-120 h) rates were 53.5, 58.8, 53.2, and 59.3 %, respectively. The addition of dexamethasone improved emetic control (acute CR rate) by at least 15 % for all groups except oral palonosetron 0.25 mg, where the acute CR improvement was approximately 7 %. Adverse events were similar in nature, incidence, and intensity for all oral and IV palonosetron groups, and were the expected adverse events for 5-HT3 RAs (primarily headache and constipation).
Oral palonosetron has a similar efficacy and safety profile as IV palonosetron 0.25 mg and may be the preferred formulation in certain clinical situations. Among the tested oral treatments, a palonosetron 0.50-mg oral dose has been favored for the prevention of CINV in patients receiving moderately emetogenic chemotherapy due to a numerical gain in efficacy without a side effect disadvantage.
帕洛诺司琼（Aloxi（®），Onicit（®））是一种具有独特药理学作用的 5-HT3 受体拮抗剂（RA），批准作为一种单一的静脉注射药物，用于预防中度致吐性化疗（MEC）和高度致吐性化疗（HEC）引起的恶心和呕吐。已经开发了一种口服帕洛诺司琼制剂，并与静脉制剂进行了比较。
在这项多中心、多国、双盲、双模拟、剂量范围的试验中，651 名患者被随机分配至接受以下任一一种单剂量治疗，用于中度致吐性化疗前：口服帕洛诺司琼 0.25、0.50 和 0.75 mg 或静脉帕洛诺司琼 0.25 mg。患者还按 1:1 随机分配至第 1 天接受静脉地塞米松 8mg 或匹配安慰剂。主要终点是急性（0-24 小时）期间完全缓解（CR；无呕吐，无解救治疗）。
所有接受帕洛诺司琼 0.25、0.50 和 0.75 mg 口服剂量以及静脉帕洛诺司琼 0.25 mg 的患者的急性 CR 率分别为 73.5%、76.3%、74.1%和 70.4%；延迟 CR（24-120 小时）率分别为 59.4%、62.5%、60.1%和 65.4%；总 CR（0-120 小时）率分别为 53.5%、58.8%、53.2%和 59.3%。除了口服帕洛诺司琼 0.25 mg 组外，地塞米松的添加至少提高了所有组的止吐控制（急性 CR 率）15%，其中急性 CR 改善约为 7%。所有口服和静脉帕洛诺司琼组的不良反应性质、发生率和强度相似，且均为 5-HT3RA 的预期不良反应（主要为头痛和便秘）。
口服帕洛诺司琼与静脉帕洛诺司琼 0.25 mg 具有相似的疗效和安全性，在某些临床情况下可能是首选制剂。在测试的口服治疗中，由于在不增加不良反应的情况下提高了疗效，因此口服帕洛诺司琼 0.50mg 已被推荐用于预防接受中度致吐性化疗的患者的 CINV。
