Machiavelli M R, Salum G, Pérez J E, Ortiz E H, Romero A O, Bologna F, Vallejo C T, Lacava J A, Dominguez M E, Leone B A
Grupo Oncológico Cooperativo del Sur, Neuquen, República Argentina.
Am J Clin Oncol. 2004 Apr;27(2):149-54. doi: 10.1097/01.coc.0000054903.27866.31.
The purpose of this report is to evaluate the efficacy and toxicity (Tx) of a double modulation of 5-fluorouracil (5-FU) by trimetrexate (TMTX) and leucovorin (LV) in patients with advanced recurrent (inoperable) or metastatic colorectal cancer (ACC). Between December 1997 and August 2000, 36 patients were entered in this phase II study. Median age was 61 years, and 18 patients (50%) were female. Median performance status was 0 (range: 0-1), whereas primary tumor location was colon in 21 patients (58%) and rectum in 15 patients (42%). The number of metastatic sites was 1:29 patients (81%); 2:6 patients (17%) and 3:1 patient (3%). Hepatic involvement was observed in 33 patients (92%). Treatment consisted of TMTX 110 mg/m2 IV over 1 hour at hour (H) 0; LV 50 mg/m2 IV over 2 hours IV infusion starting at H 18; and 5-FU 900 mg/m2 IV bolus at H 20. LV (rescue) 15 mg/m2 orally was administered every 6 hours (total 6 doses) beginning at H 24. Cycles were repeated every 2 weeks until progressive disease (PD) or severe Tx. Thirty-four patients are assessable for response (R) (two patients refused further treatment after the first course of therapy), whereas all patients were assessable for Tx. Complete response: 1 patient (3%); partial response: 4 patients (12%), with an overall objective response rate of 15% (95% CI, 1%-25%); no change: 12 patients (35%); and progressive disease: 17 patients (50%). The median time to treatment failure was 4 months and median survival was 11 months. Tx was within acceptable limits. The dose-limiting side effect was mucositis. Eight episodes of grade II or III stomatitis were observed and were responsible for dosage modifications of TMTX and 5-FU. Leukopenia was observed in 16 patients (44%); neutropenia was registered in 19 patients (53%); anemia was seen in 18 patients (50%); emesis in 22 patients (61%); and dermatitis in 3 patients (8%). There were no therapy-related deaths. The double modulation of 5-FU by TMTX and LV showed modest antitumoral activity with mild to moderate Tx.
本报告旨在评估三甲曲沙（TMTX）和亚叶酸钙（LV）对5-氟尿嘧啶（5-FU）进行双重调节治疗晚期复发性（无法手术）或转移性结直肠癌（ACC）患者的疗效和毒性（Tx）。1997年12月至2000年8月，36例患者进入该II期研究。中位年龄为61岁，18例患者（50%）为女性。中位体能状态为0（范围：0 - 1），原发肿瘤部位在结肠的患者有21例（58%），在直肠的患者有15例（42%）。转移部位数量为1个的患者有29例（81%）；2个的患者有6例（17%）；3个的患者有1例（3%）。33例患者（92%）出现肝脏受累。治疗方案为：在第0小时静脉输注三甲曲沙110 mg/m²，持续1小时；在第18小时开始静脉输注亚叶酸钙50 mg/m²，持续2小时；在第20小时静脉推注5-氟尿嘧啶900 mg/m²。从第24小时开始，每6小时口服亚叶酸钙（解救）15 mg/m²（共6剂）。每2周重复一个周期，直至疾病进展（PD）或出现严重毒性反应（Tx）。34例患者可评估疗效（R）（2例患者在第一个疗程后拒绝进一步治疗），而所有患者均可评估毒性反应（Tx）。完全缓解：1例患者（3%）；部分缓解：4例患者（12%），总客观缓解率为15%（95%可信区间，1% - 25%）；病情稳定：12例患者（35%）；疾病进展：17例患者（50%）。治疗失败的中位时间为4个月，中位生存期为11个月。毒性反应在可接受范围内。剂量限制性副作用为粘膜炎。观察到8例II级或III级口腔炎，导致三甲曲沙和5-氟尿嘧啶的剂量调整。16例患者（44%）出现白细胞减少；19例患者（53%）出现中性粒细胞减少；18例患者（50%）出现贫血；22例患者（61%）出现呕吐；3例患者（8%）出现皮炎。无治疗相关死亡。TMTX和LV对5-FU的双重调节显示出适度的抗肿瘤活性，毒性反应为轻至中度。
