Experimental and Clinical Pharmacology, Centro Di Riferimento Oncologico, National Cancer Institute, Aviano, Italy.
Medical Oncology Unit B, Centro Di Riferimento Oncologico, National Cancer Institute, Aviano, Italy.
Clin Pharmacol Ther. 2017 Jul;102(1):123-130. doi: 10.1002/cpt.615. Epub 2017 Mar 20.
The adoption of a preemptive UGT1A128 genotyping to increase irinotecan safety in clinical practice is still limited. This is the first actual study of costs associated with the management of irinotecan-related toxicities, and their association with UGT1A128 genotype. A retrospective analysis of the cost of toxicity management was conducted on 243 metastatic colorectal cancer patients enrolled in a clinical trial and treated with standard of care FOLFIRI (5-fluorouracil combined with irinotecan). The mean predicted cost per patient was higher for *28/*28 (€4,886), vs. *1/*1 (€812), (regression coefficient 1.79, 95% confidence interval (CI) = 1.31-2.28; P < 0.001) and for *1/*28 (€1,119) vs. *1/*1 (regression coefficient 0.32, 95% CI = 0.04-0.60; P = 0.024). This is consistent with a different grade 4 toxicity profile among the three genotypes, and a higher frequency of costly interventions like hospitalization among patients with the *28 allele. A differential toxicity management cost by *28 genotype is herein demonstrated, representing a first step towards the demonstration of the test clinical utility.
在临床实践中采用抢先 UGT1A128 基因分型来提高伊立替康的安全性仍然受到限制。这是第一项与管理伊立替康相关毒性相关成本及其与 UGT1A128 基因型相关的实际研究。对 243 名接受标准护理 FOLFIRI（氟尿嘧啶联合伊立替康）治疗的转移性结直肠癌患者进行了与毒性管理相关成本的回顾性分析。在临床试验中。对于 *28/*28（€4886）患者，每个患者的平均预测毒性管理成本高于 *1/*1（€812）（回归系数 1.79，95%置信区间（CI）= 1.31-2.28；P <0.001），而对于 *1/*28（€1119）患者，与 *1/*1（回归系数 0.32，95%CI = 0.04-0.60；P = 0.024）相比，成本更高。这与三种基因型之间不同的 4 级毒性特征一致，并且携带 *28 等位基因的患者更频繁地需要昂贵的干预措施，如住院治疗。在此证明了 *28 基因型的毒性管理成本存在差异，这是证明该测试临床实用性的第一步。
