BIOCHEMICAL MODULATION OF FLUOROURACIL - EVIDENCE OF SIGNIFICANT IMPROVEMENT OF SURVIVAL AND QUALITY OF LIFE IN PATIENTS WITH ADVANCED COLORECTAL-CARCINOMA
BIOCHEMICAL MODULATION OF FLUOROURACIL - EVIDENCE OF SIGNIFICANT IMPROVEMENT OF SURVIVAL AND QUALITY OF LIFE IN PATIENTS WITH ADVANCED COLORECTAL-CARCINOMA
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DOI：
10.1200/jco.1989.7.10.1407
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发表时间：
1989-10-01
影响因子：
45.3
通讯作者：
WIESENFELD, M
中科院分区：
文献类型：
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作者：
POON, MA;OCONNELL, MJ;WIESENFELD, M
本研究的目的是评估几种旨在提高氟尿嘧啶(5-FU)活性的新方法在晚期结直肠癌治疗中的有效性。429例患者被随机分为以下方案：单药5-FU，采用标准的5天强化疗程静脉推注技术；5-FU+大剂量亚叶酸钙或5-FU+小剂量亚叶酸钙；5-FU+大剂量甲氨蝶呤(MTX)口服解救；5-FU+小剂量MTX；5-FU+顺铂(CDDP)。单用5-FU的患者中位生存期为7.7个月。大剂量和小剂量亚叶酸钙联合5-FU方案的中位生存期分别为12.2个月和12.0个月，较单用5-FU方案有显著的生存优势，单侧P值分别为0.037和0.050(校正预后变量后，每次治疗P=0.051)。唯一可能与提高生存率相关的其他方案是大剂量MTX加5-FU，中位生存期为10.5个月(P=.21，P=.076)。此外，与单独使用5-FU相比，高剂量和低剂量亚叶酸钙+5-FU方案的肿瘤有效率显著提高(P=0.04和0.001)，肿瘤进展间期显著提高(P=0.015和0.007)。只有低剂量亚叶酸钙联合5-FU方案在以下生活质量参数中具有显著的优势(P<；0.05)：表现状态、体重增加和症状缓解。在这项试验中，总体上最有利的治疗方案是5-FU和低剂量的亚叶酸钙；幸运的是，这种方案与非常低的药费有关。虽然这是第一个研究表明，在晚期结直肠癌患者中，与快速静脉注射(IV)连续5天，剂量为500 mg/m2/d的5-FU相比，任何方案都可以改善缓解和生存，但收益的幅度仍然相对较小。我们的低剂量亚叶酸钙联合5-FU方案目前正在进行一项全国性的试验研究，希望这种增加的晚期疾病活动性可能会在手术辅助设置中产生更多实质性的收益。
The purpose of this study was to evaluate the effectiveness of several new approaches designed to enhance the activity of fluorouracil (5-FU) in the management of advanced colorectal cancer. A total of 429 patients were randomized to one the following regimens: single-agent 5-FU, given by standard 5-day, intensive course intravenous bolus technique; 5-FU plus high-dose folinic acid (leucovorin) or 5-FU plus low-dose leucovorin; 5-FU plus high-dose methotrexate (MTX) with oral leucovorin rescue; 5-FU plus low-dose MTX; and 5-FU plus cisplatin (CDDP). The median survival for patients receiving 5-FU alone was 7.7 months. The high- and low-dose leucovorin plus 5-FU regimens had median survivals of 12.2 and 12.0 months, respectively, and offered a significant survival advantage over 5-FU alone with one-sided P values of .037 and .050, respectively (P = .051 for each treatment after correction for prognostic variables). The only other regimen possibly associated with improved survival was high-dose MTX plus 5-FU, with a median survival at 10.5 months (P = .21, P = .076 corrected). In addition, both high- and low-dose leucovorin plus 5-FU regimens were associated with significantly improved tumor response rates (P = .04 and .001) and significantly improved interval-to-tumor-pregression rates (P = .015 and .007) when compared with 5-FU alone. Only the low-dose leucovorin plus 5-FU regimen was associated with significant (P < .05) superiority in each of the following parameters of quality of life: performance status, weight gain, and symptomatic relief. The overall most therapeutically favorable regimen in this trial was 5-FU given with low-dose leucovorin; fortuitously, this regimen is associated with very low drug cost. Whereas this is the first study to demonstrate both improved palliation and survival for any regimen compared with 5-FU given by rapid intravenous (IV) injection for 5 consecutive days at a dose of 500 mg/m2/d in patients with advanced coloerectal cancer, the magnitude of the gain is still relatively small. Our low-dose leucovorin plus 5-FU regimen is currently being studied in a national trial with the hope that this increased advanced disease activity may produce more substantive gains in the surgical adjuvant setting.