Abe Yu, Sakuyama Naoki, Sato Tsuyoshi, Kishine Kenji, Nagayasu Kiichi, Nakatani Akinori, Kitajima Masayuki, Watanabe Tomoo, Nishimura Kazuhiko, Ochiai Takumi, Nagaoka Isao
Department of Surgery, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo 125-8512, Japan.
Department of Host Defense and Biochemical Research, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
Mol Clin Oncol. 2019 Sep;11(3):289-295. doi: 10.3892/mco.2019.1893. Epub 2019 Jul 3.
5-Fluorouracil (5-FU) dosing has traditionally been based on the body surface area (BSA) in colorectal cancer treatment. However, there is accumulating evidence that dosing based on BSA may be of limited use. The purpose of the present study was to evaluate the changes in 5-FU plasma levels and tumor response as well as the severity of adverse events in patients with cancer treated with 5-FU combined chemotherapy. The dosing amount of 5-FU was determined based on the BSA. Blood samples were collected, and 5-FU plasma levels in 15 patients with colorectal cancer were measured three times (0, 22 and 40 h before and after the start of infusion) during constant-infusion of 5-FU for 46 h by an immunoassay. 5-FU plasma levels were significantly higher at 22 and 40 h compared with at 0 h (P<0.001), when all 15 patients were analyzed. Notably, the tumor response of the partial response/stable disease group showed significant increases in 5-FU plasma levels at 40 h compared with at 22 h (P<0.01), while the progressive disease group showed no significant increase. In addition, the 5-FU plasma level in the adverse event level of grade ≥2 was higher than that of grade <2 at 40 h after the start of infusion. Collectively, these observations indicated that during continuous infusion of 5-FU, the 5-FU plasma level increased significantly, and the tumor response (such as partial response, stable or progressive disease) may be influenced by the increase of 5-FU plasma level from the start of infusion. Therefore, the 5-FU plasma level may be a predictive factor for maximizing the tumor response and minimizing the risk of severe adverse events.
在结直肠癌治疗中,传统上5-氟尿嘧啶(5-FU)的给药是基于体表面积(BSA)。然而,越来越多的证据表明,基于BSA的给药可能作用有限。本研究的目的是评估接受5-FU联合化疗的癌症患者中5-FU血浆水平的变化、肿瘤反应以及不良事件的严重程度。5-FU的给药量是根据BSA确定的。采集血样,通过免疫测定法在15例结直肠癌患者持续输注5-FU 46小时期间,在输注开始前和后0、22和40小时三次测量5-FU血浆水平。当对所有15例患者进行分析时,与0小时相比,22和40小时时5-FU血浆水平显著更高(P<0.001)。值得注意的是,部分缓解/病情稳定组的肿瘤反应显示,与22小时相比,40小时时5-FU血浆水平显著升高(P<0.01),而疾病进展组则无显著升高。此外,输注开始后40小时,≥2级不良事件水平的5-FU血浆水平高于<2级。总体而言,这些观察结果表明,在持续输注5-FU期间,5-FU血浆水平显著升高,肿瘤反应(如部分缓解、病情稳定或进展)可能受输注开始后5-FU血浆水平升高的影响。因此,5-FU血浆水平可能是使肿瘤反应最大化和将严重不良事件风险最小化的一个预测因素。