Conroy T, Geoffrois L, Guillemin F, Luporsi E, Krakowski I, Spaëth D, Frasie V, Volff D
Department of Medical Oncology, Centre Alexis Vautrin, Vandoeuvre-lès-Nancy, France.
Cancer. 1993 Oct 1;72(7):2190-7. doi: 10.1002/1097-0142(19931001)72:7<2190::aid-cncr2820720721>3.0.co;2-g.
Numerous preclinical and clinical trials showed that circadian-modified 5-fluoro-2-deoxyuridine (floxuridine; FUdR) infusion administered with a totally implantable programmable pump is associated with lower toxicity, higher dose intensity, and improved therapeutic outcome in renal cell carcinoma (RCC).
Between July 1988 and March 1991, the authors treated 30 patients with metastatic RCC with circadian-timed infusion FUdR at 0.15 mg/kg/day x 14 days at monthly intervals with a programmable portable pump. Time modification was simplified with one-third of the daily dose given between 11 p.m. and 11 a.m. and two-thirds given between 11 a.m. and 11 p.m. The characteristics of the patients were as follows: 19 men; 11 women; median age, 60 years (range, 28-82 years); median World Health Organization (WHO) performance status: 2 (range: 0-3); 77% failed prior systemic treatment. The main sites of tumor involvement were lungs (70%) and bone (53%).
One hundred twenty-eight cycles were completed (median, 3 cycles per patient; range: 1-18 cycles per patient). Toxicity developed in 10 (33%) patients, primarily Grade 1-2 nausea/vomiting (6 patients), Grade 3 diarrhea (3 patients), and Grade 2 hand-foot syndrome (1 patient). In 28 patients evaluable for response, the authors observed four partial responses (14%; 95% confidence interval, 4-33%) and five stabilizations of the disease, including three minor responses. The median duration of response was 12 months (range, 8-24 months), and the median survival time was 6 months.
Circadian continuous infusion FUdR may be an effective outpatient treatment for metastatic RCC, with low toxicity and good quality of life in responding patients.
大量临床前和临床试验表明，使用完全植入式可编程泵进行昼夜节律调整的5-氟-2-脱氧尿苷（氟尿苷；FUdR）输注，在肾细胞癌（RCC）治疗中具有更低的毒性、更高的剂量强度以及更好的治疗效果。
1988年7月至1991年3月期间，作者使用可编程便携式泵，以0.15mg/kg/天的剂量，每月间隔14天，对30例转移性肾细胞癌患者进行昼夜节律定时输注氟尿苷治疗。时间调整简化为每日剂量的三分之一在晚上11点至上午11点之间给予，三分之二在上午11点至晚上11点之间给予。患者特征如下：男性19例；女性11例；中位年龄60岁（范围28 - 82岁）；世界卫生组织（WHO）体力状况评分中位数：2（范围：0 - 3）；77%患者既往全身治疗失败。肿瘤主要累及部位为肺（70%）和骨（53%）。
共完成128个周期（中位数，每位患者3个周期；范围：每位患者1 - 18个周期）。10例（33%）患者出现毒性反应，主要为1 - 2级恶心/呕吐（6例）、3级腹泻（3例）和2级手足综合征（1例）。在28例可评估反应的患者中，作者观察到4例部分缓解（14%；95%置信区间，4 - 33%）和5例病情稳定，包括3例轻微缓解。缓解持续时间中位数为12个月（范围，8 - 24个月），中位生存时间为6个月。
昼夜节律持续输注氟尿苷可能是转移性肾细胞癌有效的门诊治疗方法，毒性低，对有反应的患者生活质量良好。
