Jodrell D I, Stewart M, Aird R, Knowles G, Bowman A, Wall L, McLean C
ICRF Medical Oncology Unit, University of Edinburgh, UK.
Br J Cancer. 2001 Mar 2;84(5):600-3. doi: 10.1054/bjoc.2000.1664.
PVI 5FU gives increased response rates and reduced toxicity when compared to bolus 5FU (J Clin Oncol 1989, 425-432). PVI 5FU administration was reported to give highly variable (>1000-fold) plasma 5FU concentrations at steady state (FU Css) which correlated with toxicity (Ann Oncol 1996, 47-53); but only 19 patients were studied. Therefore, we performed a study of PVI 5FU in 61 patients with advanced colorectal cancer to assess the variability (inter- and intra-subject) in 5FU Css associated with PVI 5FU (300 mg m(-2)day(-1)) and to attempt to correlate pharmacodynamic end-points (anti-tumour activity, toxicity) with 5FU Css as a prelude to 'exposure-guided' 5FU administration. All 5FU sampling was performed between 10 am and noon. PVI 5FU administration continued to 26 weeks in patients with disease improvement or stabilization. The response rate was 26% (33% stable disease) and median survival was 11 months. Hand-foot syndrome was the most common dose limiting toxicity. Variability in 5FU(300)Css was considerably less than previously reported; 94 +/- 25 ng ml(-1)(CV = 27%). No relationships were demonstrated between subject mean 5FU(300)Css and PD end-points such as response, mucositis, diarrhoea and hand-foot syndrome. The lack of correlation suggests that measurement of 5FU concentrations should not be used to individualize dosing in patients receiving PVI 5FU for advanced colorectal cancer.
与推注5-氟尿嘧啶（5FU）相比，门静脉输注5-氟尿嘧啶（PVI 5FU）能提高缓解率并降低毒性（《临床肿瘤学杂志》1989年，第425 - 432页）。据报道，门静脉输注5-氟尿嘧啶时，稳态血浆5-氟尿嘧啶浓度（FU Css）变化很大（超过1000倍），且与毒性相关（《肿瘤学年鉴》1996年，第47 - 53页）；但仅研究了19例患者。因此，我们对61例晚期结直肠癌患者进行了一项关于门静脉输注5-氟尿嘧啶的研究，以评估与门静脉输注5-氟尿嘧啶（300 mg m(-2)天(-1)）相关的5-氟尿嘧啶稳态浓度（FU Css）的个体间和个体内变异性，并试图将药效学终点（抗肿瘤活性、毒性）与5-氟尿嘧啶稳态浓度相关联，作为“暴露导向”5-氟尿嘧啶给药的前奏。所有5-氟尿嘧啶样本采集均在上午10点至中午之间进行。对于病情改善或稳定的患者，门静脉输注5-氟尿嘧啶持续至26周。缓解率为26%（疾病稳定率为33%），中位生存期为11个月。手足综合征是最常见的剂量限制性毒性。5-氟尿嘧啶（300）稳态浓度的变异性远低于先前报道；94±25 ng/ml（CV = 27%）。未发现个体平均5-氟尿嘧啶（300）稳态浓度与反应、粘膜炎、腹泻和手足综合征等药效学终点之间存在相关性。缺乏相关性表明，对于接受门静脉输注5-氟尿嘧啶治疗晚期结直肠癌的患者，不应使用5-氟尿嘧啶浓度测量来个体化给药。
