Personeni Nicola, Giordano Laura, Michelini Angelica, D'Alessio Antonio, Cammarota Antonella, Bozzarelli Silvia, Pressiani Tiziana, Prete Maria Giuseppina, Sandri Maria Teresa, Stioui Sabine, Germagnoli Luca, Santoro Armando, Rimassa Lorenza, Mineri Rossana
Department of Biomedical Sciences, Humanitas University, Rita Levi Montalcini 4, Pieve Emanuele, 20072 Milan, Italy.
Medical Oncology and Hematology Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy.
J Pers Med. 2022 Feb 2;12(2):204. doi: 10.3390/jpm12020204.
Current guidelines recommend pre-therapeutic genotyping to guide irinotecan dosing, but the usefulness of this approach remains to be clarified. In 247 patients with advanced gastrointestinal cancers undergoing irinotecan-based chemotherapy, we prospectively performed genotyping and we analyzed the incidence of severe neutropenia according to genotype-guided dose reductions. Overall, 28 (11.3%) and 92 (37.2%) patients were homozygous or heterozygous carriers, respectively. Grade ≥ 3 neutropenia was reported in 39% of homozygous patients receiving an upfront dose reduction of irinotecan (median 40%, range 22-58%), in 20% of heterozygous or wild-type patients receiving full dose (OR = 0.38; 95% CI: 0.14-1.03; = 0.058), and in 15.3% of those receiving a reduced dose for clinical reasons (OR = 0.28, 95% IC: 0.12-0.67; = 0.004). Occurrence of severe neutropenia was inversely associated with dose reduction in homozygous carriers (OR = 0.62, 95% CI: 0.27-1.40, = 0.249) and heterozygous or wild-type patients (OR = 0.87, 95% CI: 0.59-1.28, = 0.478). Incidence of severe neutropenia was related to irinotecan doses and polymorphisms. Upfront irinotecan dose reductions do not reduce the burden of grade ≥ 3 neutropenia in homozygous carriers.
当前指南推荐进行治疗前基因分型以指导伊立替康的给药剂量，但这种方法的有效性仍有待阐明。在247例接受以伊立替康为基础化疗的晚期胃肠道癌患者中，我们前瞻性地进行了基因分型，并根据基因型指导的剂量降低分析了严重中性粒细胞减少症的发生率。总体而言，分别有28例（11.3%）和92例（37.2%）患者为纯合子或杂合子携带者。在接受伊立替康初始剂量降低的纯合子患者中，39%报告发生了≥3级中性粒细胞减少症（中位数40%，范围22 - 58%）；在接受全剂量的杂合子或野生型患者中，20%发生了≥3级中性粒细胞减少症（比值比=0.38；95%置信区间：0.14 - 1.03；P = 0.058）；在因临床原因接受剂量降低的患者中，15.3%发生了≥3级中性粒细胞减少症（比值比=0.28，95%置信区间：0.12 - 0.67；P = 0.004）。在纯合子携带者（比值比=0.62，95%置信区间：0.27 - 1.40，P = 0.249）以及杂合子或野生型患者中（比值比=0.87，95%置信区间：0.59 - 1.28，P = 0.478），严重中性粒细胞减少症的发生与剂量降低呈负相关。严重中性粒细胞减少症的发生率与伊立替康剂量和基因多态性有关。对于纯合子携带者，初始伊立替康剂量降低并不能减轻≥3级中性粒细胞减少症的负担。
