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首页> 外文期刊>Clinical colorectal cancer >Personalized dosing via pharmacokinetic monitoring of 5-fluorouracil might reduce toxicity in early- or late-stage colorectal cancer patients treated with infusional 5-fluorouracil-based chemotherapy regimens
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Personalized dosing via pharmacokinetic monitoring of 5-fluorouracil might reduce toxicity in early- or late-stage colorectal cancer patients treated with infusional 5-fluorouracil-based chemotherapy regimens

机译：通过对5-氟尿嘧啶的药代动力学监测进行个性化给药可能会降低以5-氟尿嘧啶为基础的输注化疗方案治疗的早期或晚期结直肠癌患者的毒性

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Introduction Therapeutic plasma 5-fluorouracil (5-FU) levels are achieved in only 20% to 30% of patients with the current practice of administering 5-FU doses based on body surface area (BSA). Alternatively, 5-FU doses can be adjusted based on 5-FU pharmacokinetic (PK) monitoring. Although benefits of PK monitoring of 5-FU in metastatic colorectal cancer (CRC) have been reported, its utility among patients with early stage disease has not been reported. Patients and Methods We retrospectively examined the effect of 5-FU PK monitoring in 84 CRC patients (49 stage IV and 35 stage II/III) receiving mFOLFOX6 (modifiedFOLFOX6; modified 5-fluorouracil, leucovorin, oxaliplatin protocol) or mFOLFIRI (modified 5-fluorouracil, leucovorin, irinotecan protocol). Forty-six of the 84 patients received 5-FU doses based on BSA and 38 received doses that were adjusted with PK monitoring. 5-FU plasma levels were measured using a nanoparticle immunoassay method. Results 5-fluorouracil PK monitoring significantly improved disease-free survival in stage II/III patients (P =.0429). There was also a trend towards improved progression-free survival among stage IV patients who had their 5-FU levels PK-monitored (P =.16). Moreover, 5-FU PK monitoring significantly reduced (P =.0437) and delayed (P =.0144) adverse effects in stage II/III patients. Toxicity occurred after the second 5-FU dose in the BSA group and after the sixth to seventh dose in the PK monitoring group. In stage IV patients, the onset of toxicities was also delayed with PK monitoring (P =.0605). Conclusion We provide evidence that PK monitoring of 5-FU is potentially beneficial for late stage and early stage CRC. These results contribute to the growing body of evidence regarding patient benefit when treatment decisions are based on the individual patient characteristics, in this case, a patients' 5-FU levels.
机译：简介目前，根据体表面积（BSA）施用5-FU剂量的患者中，只有20％至30％的患者达到了治疗性血浆5-氟尿嘧啶（5-FU）的水平。可选地，可以基于5-FU药代动力学（PK）监测来调节5-FU剂量。尽管已报道了PK监测5-FU在转移性结直肠癌（CRC）中的益处，但尚未报道其在早期疾病患者中的效用。患者和方法我们回顾性研究了84例接受mFOLFOX6（改良的FOLFOX6;改良的5-氟尿嘧啶，亚叶酸，奥沙利铂方案）或mFOLFIRI（改良的5-FU）的CRC患者（49阶段IV和35阶段II / III）中5-FU PK监测的效果。氟尿嘧啶，亚叶酸钙，伊立替康协议）。 84名患者中有46名接受了基于BSA的5-FU剂量，而38名接受了通过PK监测调整的剂量。使用纳米颗粒免疫测定法测量5-FU血浆水平。结果5-氟尿嘧啶PK监测显着改善了II / III期患者的无病生存期（P = .0429）。在接受5-FU水平PK监测的IV期患者中，也存在改善无进展生存的趋势（P = .16）。此外，对II / III期患者的5-FU PK监测显着降低了（P = .0437）和延迟了（P = .0144）不良反应。在BSA组中第二次5-FU给药后以及PK监测组中第六至第七次给药后发生了毒性。在IV期患者中，PK监测也延迟了毒性反应的发生（P = .0605）。结论我们提供的证据表明，对5-FU的PK监测可能对晚期和早期CRC有益。当根据个体患者的特征（在这种情况下，是患者的5-FU水平）做出治疗决定时，这些结果将为有关患者受益的证据不断增加提供帮助。

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