Seitz J F, Perrier H, Giovannini M, Capodano G, Bernardini D, Bardou V J
Unité de Gastroentérologie et d'Oncologie Digestive, Institut Paoli-Calmettes, Marseille, France.
J Chemother. 1998 Jun;10(3):258-65. doi: 10.1179/joc.1998.10.3.258.
The aim of this study was to evaluate the efficacy and tolerance of second-line continuous 5-fluorouracil (5FU) chemotherapy combined with folinic acid and mitomycin C in patients with advanced colorectal cancer who progressed on first-line chemotherapy. From June 1992 to April 1994, 24 consecutive patients, median age 59.7 years (range 41-73), performance status (PS) 0 to 2, were treated as second-line chemotherapy with mitomycin C, 7 mg/m2 every 4 weeks, folinic acid 200 mg/m2/day as a 2 h infusion followed by 400 mg/m2 of 5FU bolus and 600 mg/m2 continuous 5FU infusion for 22 h on days 1 and 2 and every 14 days; 19 patients did not respond to folinic acid and 5FU bolus regimen (in 2 patients, this was associated with pirarubicin in a continuous hepatic artery infusion) and 3 did not respond to irinotecan; 2 patients had disease progression during adjuvant chemotherapy with folinic acid and 5FU bolus. Tumor response was assessed every 12 weeks. One patient died before evaluation and 1 was lost to follow-up after 3 cycles; 7/24 patients had an objective response (29.2%, 95% confidence interval (CI): 11.0-47.4) including 2 complete responses; 7 additional patients had stable disease or minor response. Mean duration of response was 7.5 months. Median survival was 10 months and survival at 1 year was 39.4% (95% CI: 4-59.4). One patient who had a disease progression under irinotecan presented an objective response. No iatrogenic deaths occurred, nor was any grade 3 or 4 myelotoxicity seen. No hand-foot syndrome nor any cardiotoxicity arose but 2 grade II alopecia were seen. Digestive toxicities were the most frequent but with only 4 grade III toxicities (1 vomiting, 1 mucositis and 2 diarrhea) and no grade IV. With nearly 30% objective response and acceptable toxicity this treatment seems to offer a good alternative in the treatment of advanced colorectal cancers after the failure of first-line chemotherapy.
本研究旨在评估二线持续5-氟尿嘧啶（5FU）化疗联合亚叶酸和丝裂霉素C对一线化疗进展的晚期结直肠癌患者的疗效和耐受性。1992年6月至1994年4月，连续24例患者接受二线化疗，中位年龄59.7岁（范围41 - 73岁），体能状态（PS）为0至2，每4周给予丝裂霉素C 7 mg/m²，亚叶酸200 mg/m²/天静脉滴注2小时，随后在第1天和第2天及每14天给予400 mg/m²的5FU推注和600 mg/m²的5FU持续静脉滴注22小时；19例患者对亚叶酸和5FU推注方案无反应（2例患者与持续肝动脉灌注吡柔比星有关），3例对伊立替康无反应；2例患者在辅助化疗期间接受亚叶酸和5FU推注时疾病进展。每12周评估一次肿瘤反应。1例患者在评估前死亡，1例在3个周期后失访；24例患者中有7例出现客观缓解（29.2%，95%置信区间（CI）：11.0 - 47.4），包括2例完全缓解；另外7例患者病情稳定或有轻微反应。平均缓解持续时间为7.5个月。中位生存期为10个月，1年生存率为39.4%（95% CI：4 - 59.4）。1例在伊立替康治疗期间病情进展的患者出现了客观缓解。未发生医源性死亡，也未观察到3级或4级骨髓毒性。未出现手足综合征和心脏毒性，但有2例II级脱发。消化系统毒性最为常见，但只有4例III级毒性（1例呕吐、1例粘膜炎和2例腹泻），无IV级毒性。该治疗方案客观缓解率近30%且毒性可接受，似乎为一线化疗失败后的晚期结直肠癌治疗提供了一个良好的选择。
