Abstract:
Capecitabine, an oral pro-drug that is metabolized to 5-FU, has been used in clinical practice for more than 20 years, being part of the therapeutic standard for digestive and breast cancers. The use of capecitabine has been evaluated in many trials including cases diagnosed in recurrent or metastatic settings. Induction regimens or a combination with radiation therapy were evaluated in head and neck cancers, but 5-FU still remained the fluoropyrimidine used as a part of the current therapeutic standard. Quantifications of levels or ratios for enzymes are involved in the capecitabine metabolism to 5-FU but are also involved in its conversion and elimination that may lead to discontinuation, dose reduction or escalation of treatment in order to obtain the best therapeutic ratio. These strategies based on biomarkers may be relevant in the context of the implementation of precision oncology. In particular for head and neck cancers, the identification of biomarkers to select possible cases of severe toxicity requiring discontinuation of treatment, including \"multi-omics\" approaches, evaluate not only serological biomarkers, but also miRNAs, imaging and radiomics which will ensure capecitabine a role in both induction and concomitant or even adjuvant and palliative settings. An approach including routine testing of dihydropyrimidine dehydrogenase (DPD) or even the thymidine phosphorylase (TP)/DPD ratio and the inclusion of miRNAs, imaging and radiomics parameters in multi-omics models will help implement \"precision chemotherapy\" in HNC, a concept supported by the importance of avoiding interruptions or treatment delays in this type of cancer. The chemosensitivity and prognostic features of HPV-OPC cancers open new horizons for the use of capecitabine in heavily pretreated metastatic cases. Vorinostat and lapatinib are agents that can be associated with capecitabine in future clinical trials to increase the therapeutic ratio.
摘要:
卡培他滨,一种代谢为5-FU的口服前药,已经在临床实践中使用了20多年,是消化系统和乳腺癌治疗标准的一部分。卡培他滨的使用已经在许多试验中进行了评估,包括在复发或转移环境中诊断的病例。在头颈部癌症中评估了诱导方案或与放射治疗的组合,但5-FU仍然是氟嘧啶作为当前治疗标准的一部分.酶水平或比例的定量涉及卡培他滨代谢为5-FU,但也涉及其转化和消除,可能导致停药。剂量减少或增加治疗,以获得最佳的治疗比例。这些基于生物标志物的策略可能与精确肿瘤学的实施相关。特别是头颈部癌症,识别生物标志物,以选择需要停止治疗的严重毒性的可能病例,包括“多组学”方法,不仅评估血清学生物标志物,还有miRNA,成像和影像组学,这将确保卡培他滨在诱导和伴随甚至辅助和姑息设置中的作用。一种方法包括常规检测二氢嘧啶脱氢酶(DPD)或甚至胸苷磷酸化酶(TP)/DPD比率以及包含miRNA,多组学模型中的成像和影像组学参数将有助于在HNC中实施“精确化疗”,这一概念得到了避免此类癌症中断或治疗延迟的重要性的支持。HPV-OPC癌症的化学敏感性和预后特征为卡培他滨在严重预处理的转移性病例中的使用开辟了新的视野。伏立诺他和拉帕替尼是可以在未来的临床试验中与卡培他滨相关以增加治疗比例的药物。