Bajetta E, Di Bartolomeo M, Somma L, Moreschi M, Comella G, Turci D, Gebbia V, Scanni A, Bordogna G, Stampino C G
Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Cancer. 1996 Nov 15;78(10):2087-93. doi: 10.1002/(sici)1097-0142(19961115)78:10<2087::aid-cncr8>3.0.co;2-l.
Doxifluridine (5-dFUR) is a fluoropyrimidine derivative that has been shown to be active on a variety of solid tumors. The clinical use of intravenous (i.v.) 5-dFUR as a bolus injection or short term infusion has been limited because of its unpredictable severe neurotoxicity. Unlike fluorouracil (5-FU), 5-dFUR is effective when administered orally.
This randomized, parallel-group, Phase II trial of two schedules of 5-dFUR was conducted between April 1993 and September 1994. A total of 130 previously untreated patients with locally advanced or metastatic colorectal carcinoma were randomized to receive oral levo-leucovorin (1-leucovorin) 25 mg/dose followed by oral 5-dFUR 750 mg/m2 twice daily for 4 days every 12 days (arm A) or i.v. 1-leucovorin 25 mg/dose followed by i.v. 5-dFUR 3000 mg/m2 for 5 days every 21 days (arm B).
The two treatment arms were well balanced in terms of age, sex, and disease extension. Metastases were present in more than 90% of the total population, with the liver being the most common site. A median of 7 oral courses (range, 1-15) and 5 intravenous courses (range, 1-9) were administered. Intent-to-treat analysis rate of the randomized patients revealed a response rate of 15% (95% confidence interval [CI], 7-26) in arm A and 41% (95% CI, 29-54) in arm B. However, 7 cases in arm A and 12 in arm B were inadequately treated, and the response rates, according to standard analysis, were respectively 17% (95% CI, 8-28) and 51% (95% CI, 37-65). The median time to treatment failure was 4 months (range, 1-23) and 7 months (range, 1-9), respectively, for the two groups; median survival was 11 months (range, 1-24) in both groups. National Cancer Institute Grade 3 and 4 diarrhea were observed in 25% of the orally treated patients and in 18% of those receiving i.v. treatment. Stomatitis was reported mainly in arm B (15%). Mild and moderate neurotoxicity was observed in 6% of the patients in both arms; no severe neurotoxicity was reported.
5-dFUR with l-leucovorin, administered either orally or intravenously, produces response rates that are similar to those offered by the regimens containing 5-FU that are usually used to treat advanced colorectal carcinoma. This study documents the good tolerance of the i.v. schedule administered as a 1-hour infusion; furthermore, oral administration seems to be promising and feasible as a home treatment.
去氧氟尿苷（5-dFUR）是一种氟嘧啶衍生物，已显示对多种实体瘤有活性。由于其严重神经毒性不可预测，静脉注射（i.v.）5-dFUR作为大剂量注射或短期输注的临床应用受到限制。与氟尿嘧啶（5-FU）不同，5-dFUR口服有效。
1993年4月至1994年9月进行了这项关于5-dFUR两种给药方案的随机、平行组II期试验。总共130例先前未接受过治疗的局部晚期或转移性结直肠癌患者被随机分组，接受口服左亚叶酸钙（1-亚叶酸钙）25mg/剂量，随后口服5-dFUR 750mg/m²，每日两次，共4天，每12天重复（A组），或静脉注射1-亚叶酸钙25mg/剂量，随后静脉注射5-dFUR 3000mg/m²，共5天，每21天重复（B组）。
两个治疗组在年龄、性别和疾病分期方面均衡良好。转移存在于超过90%的总人群中，肝脏是最常见的转移部位。A组中位给予7个口服疗程（范围1-15），B组中位给予5个静脉疗程（范围1-9）。随机分组患者的意向性分析显示，A组缓解率为15%（95%置信区间[CI]，7-26），B组为41%（95%CI，29-54）。然而，A组7例和B组12例治疗不充分，根据标准分析，缓解率分别为17%（95%CI，8-28）和51%（95%CI，37-65）。两组治疗失败的中位时间分别为4个月（范围1-23）和7个月（范围1-9）；两组中位生存期均为11个月（范围1-24）。口服治疗患者中25%观察到美国国立癌症研究所3级和4级腹泻，静脉治疗患者中18%观察到。口腔炎主要在B组报告（15%）。两组6%的患者观察到轻度和中度神经毒性；未报告严重神经毒性。
5-dFUR联合1-亚叶酸钙，口服或静脉给药，产生的缓解率与通常用于治疗晚期结直肠癌的含5-FU方案相似。本研究证明了静脉输注1小时给药方案的良好耐受性；此外，口服给药作为家庭治疗似乎有前景且可行。
