Findlay M P, Raynaud F, Cunningham D, Iveson A, Collins D J, Leach M O
Cancer Research Campaign Section of Medicine and The GI Unit, The Institute of Cancer Research and The Royal Marsden Hospital, Surrey, UK.
Ann Oncol. 1996 Jan;7(1):47-53. doi: 10.1093/oxfordjournals.annonc.a010476.
To measure plasma 5-fluorouracil (5-FU) levels using high-performance liquid chromatography (HPLC) and compare the findings to the tissue metabolism of 5-FU evaluated using 19F magnetic resonance spectroscopy (MRS), during a protracted venous infusion (PVI) with or without interferon-alpha.
Patients receiving PVI 5-FU (300 mg/m2/day) with or without interferon-alpha (5 x 10(6) units 3 times per week), had 2 weekly plasma 5-FU levels evaluated using reverse-phase ion-pairing HPLC. These samples were drawn just prior to the patient undergoing MRS using a 1.5T Siemens Magnetom whole body magnetic resonance system with a 16 cm surface coil placed over normal liver or metastatic tumour. Semi-quantitated MRS values were compared with the plasma 5-FU levels using linear regression analysis. Data were available from patients given interferon-alpha with PVI 5-FU from day 1 or at the point of 5-FU refractory disease.
A total of 30 patients were studied. Plasma 5-FU concentrations while on a protracted venous infusion varied from <25 ng/ml (0.192 mu M) to 25,000 ng/ml (192 mu M). A high plasma 5-FU concentration was associated with an increase in patient toxicity. Patients given interferon-alpha with 5-FU had higher median plasma 5-FU levels higher than patients on 5-FU alone (6138 vs. 218 ng/ml; p = 0.03). There was no correlation between the plasma 5-FU concentration and tumour response. A comparison of the plasma 5-FU data to the MRS studies in normal liver revealed a positive correlation between plasma 5-FU and liver catabolite signal (r = 0.68; p = 0.016) but a negative correlation with the log plasma 5-FU concentration and 5-FU liver signal (r = -0.63; p = 0.022). The patients experiencing toxicity, in addition to having a higher plasma 5-FU concentration did not exhibit a liver 5-FU signal, while the reverse was true for those having no toxicity.
Plasma 5-FU levels may show greater interpatient variation when given as a protracted venous infusion. Levels of 5-FU correlated with treatment toxicity but not with anti-tumour activity. The addition of interferon-alpha to 5-FU increases plasma 5-FU levels. MRS findings suggest patients with low plasma 5-FU levels have higher 5-FU levels in normal liver tissue than in those with higher plasma levels.
在持续静脉输注（PVI）5-氟尿嘧啶（5-FU）时，无论是否联合α干扰素，使用高效液相色谱法（HPLC）测定血浆5-FU水平，并将结果与使用19F磁共振波谱（MRS）评估的5-FU组织代谢情况进行比较。
接受PVI 5-FU（300mg/m²/天）且无论是否联合α干扰素（5×10⁶单位，每周3次）的患者，每周2次使用反相离子对HPLC评估血浆5-FU水平。这些样本在患者使用1.5T西门子Magnetom全身磁共振系统进行MRS检查之前采集，该系统配备一个16cm表面线圈，置于正常肝脏或转移瘤上方。使用线性回归分析将半定量的MRS值与血浆5-FU水平进行比较。数据来自从第1天开始接受PVI 5-FU联合α干扰素治疗的患者或处于5-FU难治性疾病阶段的患者。
共研究了30例患者。持续静脉输注期间血浆5-FU浓度范围为<25ng/ml（0.192μM）至25,000ng/ml（192μM）。血浆5-FU浓度高与患者毒性增加相关。接受5-FU联合α干扰素治疗的患者血浆5-FU水平中位数高于单纯接受5-FU治疗的患者（6138 vs. 218ng/ml；p = 0.03）。血浆5-FU浓度与肿瘤反应之间无相关性。将血浆5-FU数据与正常肝脏的MRS研究结果进行比较，发现血浆5-FU与肝脏分解代谢物信号呈正相关（r = 0.68；p = 0.016），但与血浆5-FU浓度对数和5-FU肝脏信号呈负相关（r = -0.63；p = 0.022）。出现毒性的患者除血浆5-FU浓度较高外，未表现出肝脏5-FU信号，而无毒性的患者情况则相反。
持续静脉输注5-FU时，患者间血浆5-FU水平可能存在较大差异。5-FU水平与治疗毒性相关，但与抗肿瘤活性无关。5-FU联合α干扰素可提高血浆5-FU水平。MRS结果表明，血浆5-FU水平低的患者正常肝脏组织中的5-FU水平高于血浆水平高的患者。
