Phase II study of preoperative radiation plus concurrent daily tegafur-uracil (UFT) with leucovorin for locally advanced rectal cancer
Phase II study of preoperative radiation plus concurrent daily tegafur-uracil (UFT) with leucovorin for locally advanced rectal cancer
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术前放疗联合每日替加氟尿嘧啶 (UFT) 联合亚叶酸治疗局部晚期直肠癌的 II 期研究
作者：
P. Cellier;B. Leduc;L. Martin;B. Vié;C. Chevelle;V. Vendrely;A. Salemkour;C. Carrie;G. Calais;P. Burtin;L. Campion;M. Boisdron;A. Morel;V. Berger;E. Gamelin
背景由于二氢嘧啶脱氢酶（DPD）的酶活性范围广泛，静脉注射5-氟尿嘧啶（5-FU）的代谢可能发生相当大的变化，这可能影响耐受性和疗效。口服氟嘧啶替加氟尿嘧啶（UFT）是静脉注射5-FU的有效、耐受性良好且方便的替代方案。我们在局部晚期直肠癌患者中进行了这项研究，以评估UFT联合亚叶酸（LV）和术前放疗的疗效和耐受性，并评估多中心分期的实用性和局限性，使用术前和术后放化疗超声。我们还进行了一个有效的治疗前评估DPD活性和评估其对UFT treatment.MethodsThis的耐受性的潜在影响，第二阶段的研究评估术前UFT与LV和放疗85例局部晚期T3直肠癌。具有潜在可切除肿瘤的患者接受UFT（300 mg/m/2/天）、LV（75 mg/天）和盆腔放疗（1.8戈伊/天，总计45戈伊），每周5天，持续5周，然后在4-6周后手术。主要终点包括肿瘤的降级和病理完全反应（pCR）率。结果大多数不良事件是轻度至中度的性质。术前3/4级不良事件包括腹泻（n = 18，21%）和恶心/呕吐（n = 5，6%）。二氢嘧啶脱氢酶基因（DPYD）杂合子的两名患者经历了早期4级中性粒细胞减少症（变体IVS 14 +1G > A）和腹泻（变体2846 A> T）。将治疗前超声TNM分期与放化疗后病理TN分期进行比较，观察到TNM分期明显向早期转移（p < 0.001）。原发性肿瘤的总体降级率为42%，淋巴结为44%。pCR率为8%。超声分期的敏感性和特异性较差。55例患者（65%）保留了肛门括约肌功能。3年总生存率和无复发生存率分别为86.1%和66.7%。36淋巴结阳性患者（平均持续时间118天）进行辅助化疗。结论术前放化疗使用UFT与LV加放疗耐受性良好，有效，是一种方便的替代5-FU为基础的放化疗治疗可切除的直肠癌。应进行DPD缺乏症的治疗前检测，以避免严重的不良事件。
BackgroundConsiderable variation in intravenous 5-fluorouracil (5-FU) metabolism can occur due to the wide range of dihydropyrimidine dehydrogenase (DPD) enzyme activity, which can affect both tolerability and efficacy. The oral fluoropyrimidine tegafur-uracil (UFT) is an effective, well-tolerated and convenient alternative to intravenous 5-FU. We undertook this study in patients with locally advanced rectal cancer to evaluate the efficacy and tolerability of UFT with leucovorin (LV) and preoperative radiotherapy and to evaluate the utility and limitations of multicenter staging using pre- and post-chemoradiotherapy ultrasound. We also performed a validated pretherapy assessment of DPD activity and assessed its potential influence on the tolerability of UFT treatment.MethodsThis phase II study assessed preoperative UFT with LV and radiotherapy in 85 patients with locally advanced T3 rectal cancer. Patients with potentially resectable tumors received UFT (300 mg/m/2/day), LV (75 mg/day), and pelvic radiotherapy (1.8 Gy/day, 45 Gy total) 5 days/week for 5 weeks then surgery 4-6 weeks later. The primary endpoints included tumor downstaging and the pathologic complete response (pCR) rate.ResultsMost adverse events were mild to moderate in nature. Preoperative grade 3/4 adverse events included diarrhea (n = 18, 21%) and nausea/vomiting (n = 5, 6%). Two patients heterozygous for dihydropyrimidine dehydrogenase gene (DPYD) experienced early grade 4 neutropenia (variant IVS14+1G > A) and diarrhea (variant 2846A > T). Pretreatment ultrasound TNM staging was compared with postchemoradiotherapy pathology TN staging and a significant shift towards earlier TNM stages was observed (p < 0.001). The overall downstaging rate was 42% for primary tumors and 44% for lymph nodes. The pCR rate was 8%. The sensitivity and specificity of ultrasound for staging was poor. Anal sphincter function was preserved in 55 patients (65%). Overall and recurrence-free survival at 3 years was 86.1% and 66.7%, respectively. Adjuvant chemotherapy was administered to 36 node-positive patients (mean duration 118 days).ConclusionPreoperative chemoradiotherapy using UFT with LV plus radiotherapy was well tolerated and effective and represents a convenient alternative to 5-FU-based chemoradiotherapy for the treatment of resectable rectal cancer. Pretreatment detection of DPD deficiency should be performed to avoid severe adverse events.
影响因子：
45.3
作者：
Ryan, DP;Niedzwiecki, D;Mayer, RJ
通讯作者：
Mayer, RJ
DOI：
10.1016/0360-3016(95)00020-y
发表时间：
1995
期刊：
International journal of radiation oncology, biology, physics
影响因子：
--
作者：
Rich,TA;Skibber,JM;Ajani,JA;Buchholz,DJ;Cleary,KR;Dubrow,RA;Levin,B;Lynch,PM;Meterissian,SH;Roubein,LD
通讯作者：
Roubein,LD