Rothenberg M L, Benedetti J K, Macdonald J S, Seay T E, Neubauer M A, George C S, Tanaka M S, Giguere J K, Pruitt B T, Abbruzzese J L
Vanderbilt University Medical Center, Nashville, TN 37232-6307, USA.
Ann Oncol. 2002 Oct;13(10):1576-82. doi: 10.1093/annonc/mdf274.
Eniluracil is a potent, irreversible inactivator of dihydropyrimidine dehydrogenase, the major catabolic enzyme for 5-fluorouracil (5-FU). Pretreatment with eniluracil significantly increases plasma half-life, plasma concentration and oral bioavailability of 5-FU. This multicenter phase II trial was designed to estimate the 6-month survival rate in patients with metastatic adenocarcinoma of the pancreas treated with 5-FU and eniluracil.
One hundred and sixteen patients (61 with no prior chemotherapy and 55 with prior chemotherapy) were registered for treatment with eniluracil 50 mg (total dose) p.o. on days 1-7 and 5-FU 20 mg/m(2)/day p.o. on days 2-6 of a 28-day treatment cycle.
In 106 patients evaluable for survival, the 6-month survival rate was 34% [95% confidence interval (CI) 22% to 47%, median survival 3.6 months] for patients who had not been treated previously with chemotherapy and 29% (95% CI 16% to 42%, median survival 3.4 months) for those who had received prior chemotherapy. For those patients with measurable disease, the confirmed response rates were 8% and 2%, respectively. The most common grade 3-4 toxicities were neutropenia (29% of patients) and diarrhea (12% of patients). Overall, 69% of patients experienced a grade 3 or worse adverse event during treatment.
These results suggest that the combination of a 7-day course of eniluracil and a 5-day course of oral 5-FU has limited activity in patients with advanced pancreatic cancer, and is associated with a high frequency of clinically significant adverse events.
依那西普是一种强效、不可逆的二氢嘧啶脱氢酶灭活剂，二氢嘧啶脱氢酶是5-氟尿嘧啶（5-FU）的主要分解代谢酶。用依那西普预处理可显著提高5-FU的血浆半衰期、血浆浓度和口服生物利用度。这项多中心II期试验旨在评估接受5-FU和依那西普治疗的胰腺转移性腺癌患者的6个月生存率。
116例患者（61例未接受过化疗，55例接受过化疗）登记接受治疗，在28天治疗周期的第1 - 7天口服依那西普50mg（总剂量），第2 - 6天口服5-FU 20mg/m²/天。
在106例可评估生存情况的患者中，未接受过化疗的患者6个月生存率为34%[95%置信区间（CI）22%至47%，中位生存期3.6个月]，接受过化疗的患者为29%（95%CI 16%至42%，中位生存期3.4个月）。对于那些有可测量疾病的患者，确认的缓解率分别为8%和2%。最常见的3 - 4级毒性是中性粒细胞减少（29%的患者）和腹泻（12%的患者）。总体而言，69%的患者在治疗期间经历了3级或更严重的不良事件。
这些结果表明，7天疗程的依那西普和5天疗程的口服5-FU联合应用在晚期胰腺癌患者中的活性有限，且与高频率的具有临床意义的不良事件相关。
