Delaunoit Thierry, Goldberg Richard M, Sargent Daniel J, Morton Roscoe F, Fuchs Charles S, Findlay Brian P, Thomas Sachdev P, Salim Muhammad, Schaefer Paul L, Stella Philip J, Green Erin, Mailliard James A
Department of Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Cancer. 2004 Nov 15;101(10):2170-6. doi: 10.1002/cncr.20594.
Intergroup Trial N9741 evaluated 5-fluorouracil (5-FU)/leucovorin (LV) administered in conjunction with either irinotecan or oxaliplatin in the first-line treatment of advanced colorectal carcinoma (CRC). The current report describes two treatment arms that were withdrawn from the protocol due to unexpected treatment-related toxicities and a high mortality rate. The complications observed in these arms highlight the importance of aggressive and immediate supportive care in the management of digestive toxicity.
In Trial N9741, patients were randomly assigned to receive one of the following six regimens: 1) irinotecan plus bolus 5-FU/LV (Arm A); 2) sequential irinotecan plus bolus 5-FU/LV (Arm B); 3) bolus 5-FU/LV only (Mayo Clinic regimen; Arm D); 4) oxaliplatin plus bolus 5-FU/LV (Arm E); 5) oxaliplatin plus infusional 5-FU/LV (Arm F); or 6) oxaliplatin plus irinotecan (Arm G). In the current study, the authors investigated treatment-related toxicity in patients who received either of the two combination regimens containing daily bolus 5-FU (i.e., patients in Arm B or Arm E).
Sixty-one and 47 patients were enrolled in Arm B and Arm E, respectively. Diarrhea and neutropenia were the most common toxicities in both groups. Five patients in Arm B (8.2%) and 4 patients in Arm E (8.5%) died within 60 days of study entry. All fatal toxicities occurred within 15 days of treatment administration, and all deaths were associated with the simultaneous occurrence of multiple symptoms, which were dominated by Grade > or = 3 diarrhea.
Combination regimens containing daily bolus 5-FU/LV and oxaliplatin or irinotecan can be associated with severe gastrointestinal toxicity and high mortality rates. Therefore, the authors recommend the use of more tolerable infusional 5-FU-based regimens in the treatment of metastatic CRC.
N9741组间试验评估了在晚期结直肠癌（CRC）一线治疗中，5-氟尿嘧啶（5-FU）/亚叶酸钙（LV）联合伊立替康或奥沙利铂的疗效。本报告描述了因意外的治疗相关毒性和高死亡率而从方案中撤出的两个治疗组。在这些组中观察到的并发症突出了积极和立即的支持治疗在消化毒性管理中的重要性。
在N9741试验中，患者被随机分配接受以下六种方案之一：1）伊立替康加推注5-FU/LV（A组）；2）序贯伊立替康加推注5-FU/LV（B组）；3）仅推注5-FU/LV（梅奥诊所方案；D组）；4）奥沙利铂加推注5-FU/LV（E组）；5）奥沙利铂加持续输注5-FU/LV（F组）；或6）奥沙利铂加伊立替康（G组）。在本研究中，作者调查了接受两种含每日推注5-FU的联合方案之一的患者（即B组或E组患者）的治疗相关毒性。
B组和E组分别入组了61例和47例患者。腹泻和中性粒细胞减少是两组中最常见的毒性。B组有5例患者（8.2%）和E组有4例患者（8.5%）在研究入组后60天内死亡。所有致命毒性均发生在治疗给药后15天内，所有死亡均与多种症状同时出现有关，其中以≥3级腹泻为主。
含每日推注5-FU/LV和奥沙利铂或伊立替康的联合方案可能会导致严重的胃肠道毒性和高死亡率。因此，作者建议在转移性CRC的治疗中使用耐受性更好的基于持续输注5-FU的方案。
