Smith I E, Johnston S R, O'Brien M E, Hickish T F, de Boer R H, Norton A, Cirkel D T, Barton C M
Royal Marsden Hospital, Sutton and London, UK.
J Clin Oncol. 2000 Jun;18(12):2378-84. doi: 10.1200/JCO.2000.18.12.2378.
Eniluracil (776C85) is an effective inactivator of dihydropyrimidine dehydrogenase that allows continuous low-dose oral fluorouracil (5-FU) to be given with predicable oral bioavailability. We have assessed this as first-line oral chemotherapy for patients with advanced/metastatic breast cancer.
Patients with histologically proven, locally advanced or metastatic breast cancer without previous chemotherapy for advanced disease were entered onto this open-label phase II study. Patients received oral 5-FU 1.0 mg/m(2) with eniluracil 10 mg/m(2), both given twice daily for the first 28 days of each 35-day cycle, continuing until disease progression or unmanageable toxicity.
Thirty-three patients were entered, with a median age of 53 years. Sixteen partial responses were seen in twenty-nine assessable patients (55%; 95% confidence interval, 37% to 73%), including responses in four (40%) out of 10 patients who had received prior adjuvant 5-FU. Seven patients had stable disease for at least 3 months with symptom improvement. Median response duration was 14 months (range, 10 to 18+ months). Toxicity was low. There were only two episodes of drug-related grade 3 nonhematologic toxicity (diarrhea and infection), and only 6%, 3%, and 3% of patients developed granulocytopenia, thrombocytopenia, and neutropenic sepsis, respectively. Mild (grade 1/2) diarrhea occurred in 39% of patients, hand-foot syndrome in 15%, nausea in 27%, and mucositis in 18%. Toxicity-associated delay and dose reduction occurred in only 2% and 5% of courses, respectively.
First-line treatment with the combination of oral 5-FU and eniluracil has high activity in patients with advanced breast cancer comparable with the most active conventional cytotoxic agents but with strikingly less toxicity.
乙磺嘧啶（776C85）是一种有效的二氢嘧啶脱氢酶灭活剂，可使连续低剂量口服氟尿嘧啶（5-氟尿嘧啶）具有可预测的口服生物利用度。我们已将此评估为晚期/转移性乳腺癌患者的一线口服化疗方案。
组织学确诊、局部晚期或转移性乳腺癌且未接受过晚期疾病化疗的患者进入这项开放标签的II期研究。患者接受口服5-氟尿嘧啶1.0mg/m²及乙磺嘧啶10mg/m²，两者均在每个35天周期的前28天每日给药两次，持续至疾病进展或出现无法耐受的毒性反应。
33例患者入组，中位年龄53岁。29例可评估患者中有16例出现部分缓解（55%；95%置信区间，37%至73%），包括10例接受过辅助性5-氟尿嘧啶治疗的患者中有4例（40%）出现缓解。7例患者病情稳定至少3个月且症状改善。中位缓解持续时间为14个月（范围，10至18 +个月）。毒性较低。仅出现两例与药物相关的3级非血液学毒性反应（腹泻和感染），分别仅有6%、3%和3%的患者发生粒细胞减少、血小板减少和中性粒细胞减少性败血症。39%的患者出现轻度（1/2级）腹泻，15%出现手足综合征，27%出现恶心，18%出现黏膜炎。与毒性相关的治疗延迟和剂量减少分别仅发生在2%和5%的疗程中。
口服5-氟尿嘧啶与乙磺嘧啶联合进行一线治疗对晚期乳腺癌患者具有高活性，与最有效的传统细胞毒性药物相当，但毒性显著更低。
