Jodrell D I, Murray L S, Reed N S, Canney P A, Kaye S B, Cassidy J
CRC Department of Medical Oncology, Beatson Oncology Centre, Glasgow, UK.
Br J Cancer. 1994 Oct;70(4):749-52. doi: 10.1038/bjc.1994.389.
Bolus/infusional 5-fluorouracil (5-FU) and folinic acid (FA) is reported to be highly active [partial response (PR) = 54%, median survival 18 months] in patients with metastatic colorectal carcinoma (MCCa). To confirm this level of activity, we conducted a retrospective analysis of 95 previously untreated patients with MCCa treated with FA by 2 h i.v. infusion (200 mg m-2) followed by 5-FU bolus/22 h i.v. infusion (300-500 mg m-2) on days 1 and 2 every 2 weeks. Thirty patients also received N-(phosphonacetyl)-L-aspartate (PALA), 250 mg m-2, 24 h prior to 5-FU/FA. In 81 evaluable patients, the response rate was low: PR = 11%, stable disease (SD) = 36% and median survival = 8 months. There was an improvement in survival with increased 5-FU dosage (500 mg m-2) [relative hazard (RH) = 0.38, 95% CI 0.21-0.70], controlled for age, primary site, PALA, liver function and performance status. Good performance status (PS 0 or 1) was also associated with improved survival (RH = 0.21, 95% CI 0.10-0.46). Response, survival and toxicity were not altered by the co-administration of PALA. Bolus/infusional 5-FU (500 mg m-2) and FA was well tolerated. WHO toxicities (grade 3) were: mucositis, 2%; diarrhoea, 14%; nausea and vomiting, 5%. In light of the apparent dose effect, poor response and low toxicity, we recommend that regimes incorporating higher 5-FU dosages are explored and prospectively validated before bolus/infusional 5-FU becomes accepted standard practice.
据报道，推注/输注5-氟尿嘧啶（5-FU）和亚叶酸（FA）对转移性结直肠癌（MCCa）患者具有高活性[部分缓解（PR）=54%，中位生存期18个月]。为证实这一活性水平，我们对95例先前未接受过治疗的MCCa患者进行了回顾性分析，这些患者接受FA静脉输注2小时（200mg/m²），随后在每2周的第1天和第2天推注5-FU/静脉输注22小时（300 - 500mg/m²）。30例患者在5-FU/FA前24小时还接受了N-（膦酰基乙酰基）-L-天冬氨酸（PALA），250mg/m²。在81例可评估患者中，缓解率较低：PR = 11%，疾病稳定（SD）= 36%，中位生存期 = 8个月。在控制年龄、原发部位、PALA、肝功能和体能状态的情况下，5-FU剂量增加（500mg/m²）可改善生存期[相对风险（RH）= 0.38，95%置信区间0.21 - 0.70]。良好的体能状态（PS 0或1）也与生存期改善相关（RH = 0.21，95%置信区间0.10 - 0.46）。PALA的联合使用未改变缓解率、生存期和毒性。推注/输注5-FU（500mg/m²）和FA耐受性良好。世界卫生组织定义的3级毒性为：黏膜炎，2%；腹泻，14%；恶心和呕吐，5%。鉴于明显的剂量效应、缓解不佳和低毒性，我们建议在推注/输注5-FU成为公认的标准治疗方法之前，探索并前瞻性验证包含更高5-FU剂量的治疗方案。
