Abstract

Drug resistance and toxicity are the most widespread limitations in the pursuit of sufficient antitumor effectiveness and successful control of oncological diseases, including colorectal cancer (CRC). Herein the objective was to investigate some hematological side effects of the chemotherapeutic regimen FOLFOX-4, their relation to dihydropyrimidine dehydrogenase (DPD) levels and the associated alterations in CRC patients’ plasma free-radical scavenging properties and extent of oxidative molecular damage. Thirty-eight patients with histologically confirmed CRC diagnoses, assigned to chemotherapy with the FOLFOX-4 regimen, were recruited. The diagnostic methods included a complete physical examination, blood routine test and general biochemistry. The DPD levels were assayed. The patients’ plasma free-radical scavenging properties and extent of molecular oxidative damage were determined by spectrophotometry and enhanced chemiluminescence. The clinico-pathological and demographics characteristics of the patients were in agreement with the reports from retrospective cohort studies. The FOLFOX-4 regimen induced a decrease in plasma free-radical scavenging properties and increased extent of lipid peroxidation. White blood cells, granulocytes and lymphocytes decreased significantly after the first cycle of the therapy. The patients’ DPD level decreased statistically significantly in the case of severe reduction (more than 25%) of white blood cells and granulocyte counts. The obtained data are in agreement with already known facts concerning the side effects of the FOLFOX-4 regimen and associated changes in redox homeostasis. Genetic predisposition to effectively metabolize and tolerate the applied therapy, i.e. DPD levels, could modulate some aspects of the observed changes in the aforementioned parameters.

摘要

在追求足够的抗肿瘤有效性和成功控制包括结直肠癌 (CRC) 在内的肿瘤疾病方面，耐药性和毒性是最普遍的限制。本文的目的是研究化疗方案 FOLFOX-4 的一些血液学副作用、它们与二氢嘧啶脱氢酶 (DPD) 水平的关系以及 CRC 患者血浆自由基清除特性和氧化分子损伤程度的相关改变。招募了 38 名经组织学确诊为 CRC 的患者，这些患者被分配到 FOLFOX-4 方案化疗。诊断方法包括完整的体格检查、血常规检查和一般生化检查。测定了 DPD 水平。患者的血浆自由基清除特性和分子氧化损伤的程度通过分光光度法和增强化学发光法测定。患者的临床病理学和人口统计学特征与回顾性队列研究的报告一致。FOLFOX-4 方案导致血浆自由基清除特性降低和脂质过氧化程度增加。在第一个治疗周期后，白细胞、粒细胞和淋巴细胞显着减少。在白细胞和粒细胞计数严重减少（超过25%）的情况下，患者的DPD水平有统计学意义的显着下降。获得的数据与关于 FOLFOX-4 方案的副作用和氧化还原稳态相关变化的已知事实一致。有效代谢和耐受应用疗法的遗传倾向，即 DPD 水平，可以调节上述参数中观察到的变化的某些方面。