University of Illinois at Chicago, South Wood Street, Chicago, IL, USA.
BMC Health Serv Res. 2012 Jul 23;12:215. doi: 10.1186/1472-6963-12-215.
1st generation 5-hydroxytryptamine receptor antagonists (5-HT3 RAs), and palonosetron, a 2nd generation 5-HT3 RA, are indicated for the prevention of chemotherapy (CT)-induced nausea and vomiting (CINV) associated with moderately (MEC) and highly emetogenic CT agents (HEC). This study explores the impact of step therapy policies requiring use of an older 5-HT3 RA before palonosetron on risk of CINV associated with hospital or emergency department (ED) admissions.
Patients who received cyclophosphamide post breast cancer (BC) surgery or who were diagnosed with lung cancer on carboplatin (LC-carboplatin) or cisplatin (LC-cisplatin) were selected from PharMetrics' (IMS LifeLink) claims dataset (2005-2008). Patients were followed for 6 months from initial CT administration for CINV events identified through ICD-9-CM codes. Patients were grouped into those initiated with older, generic 5-HT3 RAs (ondansetron, granisetron, and dolasetron) and those initiated and maintained on palonosetron throughout study follow-up. CINV events and CINV days were analyzed using multivariate regressions controlling for demographic and clinical variables.
Eligible patients numbered 3,606 in BC, 4,497 in LC-carboplatin and 1,154 in LC-cisplatin cohorts, with 52%, 40%, and 34% in the palonosetron group, respectively. There was no significant difference between the two 5-HT3 RA groups in age or Charlson Comorbidity Index among the two MEC cohorts (BC and LC-carboplatin). Among the LC-cisplatin cohort, palonosetron users were older with more males than the older 5-HT3 RA group (age: 60.1 vs. 61.3; males, 66.9% vs. 56.9%). Compared to the older 5-HT3 RAs, the palonosetron groups incurred 22%-51% fewer 5-HT3 RA pharmacy claims, had fewer patients with CINV events (3.5% vs. 5.5% in BC, 9.5% vs. 12.8% in LC-carboplatin, 16.4% vs. 21.7% in LC-cisplatin), and had lower risk for CINV events (odds ratios 0.62, 0.71, or 0.71, respectively; p<0.05). The BC and LC-carboplatin palonosetron groups experienced 50% and 30% fewer CINV days than the generic 5-HT3 RA group (p<0.05).
Patients with breast or lung cancer initiated and maintained on palonosetron were at significantly lower risk for potentially costly CINV versus those on older 5-HT3 RAs. Further studies on impact of step therapy policy are warranted in order to minimize the clinical and economic burden of CINV.
第一代 5-羟色胺受体拮抗剂（5-HT3 RAs）和帕洛诺司琼（第二代 5-HT3 RA）适用于预防与中度致吐化疗（MEC）和高度致吐化疗药物（HEC）相关的化疗（CT）引起的恶心和呕吐（CINV）。本研究探讨了需要在使用帕洛诺司琼之前使用较旧的 5-HT3 RA 的分步治疗政策对与住院或急诊（ED）入院相关的 CINV 风险的影响。
从 PharMetrics（IMS LifeLink）的索赔数据集（2005-2008 年）中选择接受乳腺癌（BC）手术后环磷酰胺或诊断为肺癌的卡铂（LC-卡铂）或顺铂（LC-顺铂）的患者。从初始 CT 给药开始，通过 ICD-9-CM 代码确定 CINV 事件，对患者进行为期 6 个月的随访。根据 5-HT3 RA 初始使用情况将患者分为使用较旧的通用 5-HT3 RA（昂丹司琼、格拉司琼和多拉司琼）和整个研究随访期间使用和维持帕洛诺司琼的患者。使用多元回归分析控制人口统计学和临床变量来分析 CINV 事件和 CINV 天数。
在 BC、LC-卡铂和 LC-顺铂队列中，符合条件的患者人数分别为 3606 例、4497 例和 1154 例，帕洛诺司琼组分别为 52%、40%和 34%。在两个 MEC 队列（BC 和 LC-卡铂）中，两种 5-HT3 RA 组之间在年龄或 Charlson 合并症指数方面没有显著差异。在 LC-顺铂队列中，与较旧的 5-HT3 RA 组相比，帕洛诺司琼组的患者年龄更大，男性更多（年龄：60.1 对 61.3；男性，66.9%对 56.9%）。与较旧的 5-HT3 RA 相比，帕洛诺司琼组的 5-HT3 RA 药房配药次数减少了 22%-51%，CINV 事件患者更少（BC 为 3.5%对 5.5%，LC-卡铂为 9.5%对 12.8%，LC-顺铂为 16.4%对 21.7%），CINV 事件风险较低（比值比分别为 0.62、0.71 或 0.71；p<0.05）。BC 和 LC-卡铂帕洛诺司琼组的 CINV 天数比通用 5-HT3 RA 组减少了 50%和 30%（p<0.05）。
与使用较旧的 5-HT3 RA 相比，开始并维持使用帕洛诺司琼的乳腺癌或肺癌患者发生潜在昂贵的 CINV 的风险显著降低。需要进一步研究分步治疗政策的影响，以尽量减少 CINV 的临床和经济负担。
