Bianchino Gabriella, Perrone Alessandra, Sgambato Alessandro, Sarno Italo, Nozza Filomena, Omer Ludmila Carmen, Ulivi Massimo, Traficante Antonio, Campisi Biagina, Russi Sabino, Calice Giovanni, Falco Geppino, Tartarone Alfredo
Unit of Clinical Pathology IRCCS-CROB Referral Cancer Center of Basilicata, Rionero in Vulture, PZ, Italy.
Department of Onco-Hematology, Division of Medical Oncology, IRCCS-CROB Referral Cancer Center of Basilicata, Rionero in Vulture, PZ, Italy.
J Chemother. 2025 Apr 17:1-7. doi: 10.1080/1120009X.2025.2489837.
Fluoropyrimidines (FPs) are antineoplastic agents used for the treatment of various solid tumors, especially gastrointestinal cancers. Patients with variations in dihydropyrimidine dehydrogenase gene (), which can determine the partial or complete deficiency of the dihydropyrimidine dehydrogenase enzyme (DPD), are at an increased risk of developing severe and potentially life-threatening toxicity. Worldwide the introduction of pharmacogenetic testing into clinical practice has been a slow process and in our center the analysis of the gene has been adopted since April 2020. We evaluated the clinical application of routine DPYD screening and its ability to prevent early-onset of fluoropyrimidine-related toxicity in patients treated at the Oncology Reference Center of Basilicata (IRCCS-CROB), a recognized cancer centre in Southern Italy. From April 2020 to November 2022, 300 patients (male 137; female 163) diagnosed with various types of cancer were subjected to genotyping, before starting treatment with FPs. In accordance with the current European Medicines Agency (EMA) and the Italian Association of Medical Oncology (AIOM) guidelines patients were tested for four variants that are associated with reduced DPD activity. FPs dose adjustments in variant carriers were made following the previously mentioned guidelines. Three hundred patients underwent testing and thirteen (4.3%) patients were found to be heterozygous variant carriers; ten out of thirteen patients received FP dose reduction as indicated by the guidelines, one out of thirteen patients received alternative treatment, two of the thirteen patients received no treatment at all. The main toxicities observed in patients who received a genotype-based dose reduction were anemia, neutropenia, nausea and mucositis but events were primarily grade 1 or 2. Our experience confirms the technical feasibility and the usefulness of genotyping to reduce the risk of severe FPs toxicities.
氟嘧啶（FPs）是用于治疗各种实体瘤，尤其是胃肠道癌症的抗肿瘤药物。二氢嘧啶脱氢酶基因（）存在变异的患者，该基因可决定二氢嘧啶脱氢酶（DPD）部分或完全缺乏，其发生严重且可能危及生命的毒性的风险会增加。在全球范围内，将药物遗传学检测引入临床实践是一个缓慢的过程，在我们中心，自2020年4月起开始采用对该基因的分析。我们评估了常规DPYD筛查在意大利南部公认的癌症中心巴西利卡塔肿瘤参考中心（IRCCS - CROB）接受治疗的患者中的临床应用及其预防氟嘧啶相关毒性早期发作的能力。从2020年4月到2022年11月，300例被诊断患有各种癌症的患者（男性137例；女性163例）在开始使用FPs治疗前进行了基因分型。根据当前欧洲药品管理局（EMA）和意大利医学肿瘤学协会（AIOM）的指南，对患者进行了与DPD活性降低相关的四种变异检测。对变异携带者的FPs剂量调整遵循上述指南进行。300例患者接受了检测，发现13例（4.3%）患者为杂合变异携带者；13例患者中有10例按照指南接受了FPs剂量降低，13例患者中有1例接受了替代治疗，13例患者中有2例根本未接受治疗。在接受基于基因型剂量降低的患者中观察到的主要毒性为贫血、中性粒细胞减少、恶心和粘膜炎，但事件主要为1级或2级。我们的经验证实了基因分型在降低严重FPs毒性风险方面的技术可行性和实用性。
