Phase I study of CPT-11 and bolus 5-FU/l-leucovorin in patients with metastatic colorectal cancer
Phase I study of CPT-11 and bolus 5-FU/l-leucovorin in patients with metastatic colorectal cancer
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DOI：
10.1007/s10147-003-0371-3
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发表时间：
2004-04
影响因子：
3.3
通讯作者：
H. Fujishima;I. Kikuchi;O. Miyanaga;A. Ueda;E. Baba;K. Mitsugi;M. Harada;S. Nakano
中科院分区：
文献类型：
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作者：
H. Fujishima;I. Kikuchi;O. Miyanaga;A. Ueda;E. Baba;K. Mitsugi;M. Harada;S. Nakano
背景：迪立替康（CPT-11）和5-氟尿嘧啶(5-FU)/亚叶酸素（LV）每周给药，每42天给药4周（Saltz方案）对转移性结直肠癌（CRC）患者有效，但毒性很大。然而，该方案在日本转移性结直肠癌患者中的疗效和毒性尚未确定。方法：我们研究了日本转移性结直肠癌患者CPT-11的最大耐受剂量（MTD）、剂量限制毒性（DLT）和推荐II期剂量（RD），分别给予静脉注射（输注90分钟）和每周注射5-FU加生物活性lv（改良Saltz方案），每28天给药3周。入选18例可测量疾病、东部肿瘤合作组（ECOG）评分为2分或以下、器官功能正常的患者。结果2级剂量（CPT-11, 100 mg/m2; 5-FU, 400 mg/m2; l- lv， 25 mg/体），6例患者中有1例发生发热性中性粒细胞减少症（DLT）。在剂量水平3 （CPT-11, 100 mg/m2; 5-FU, 500 mg/m2; l- lv， 25 mg/体）时，6例患者中有2例发生DLT（发热性中性粒细胞减少症和4级中性粒细胞减少症持续4天以上）。为了确定3级是否为MTD水平，另外3例患者在该水平治疗，但未观察到DLT。因此，9例患者中有2例DLT达到3级，因此该级别被认为是RD。在该级别，3 - 4级中性粒细胞减少症很常见，但可以控制。非血液学毒性较轻。在18例入组患者中观察到7例部分缓解（缓解率[RR]， 39%）， 8例患者（44%）病情稳定。结论CPT-11/5-FU/l-LV方案每周给药，每28天给药3周，具有显著的抗肿瘤活性，毒性可控。一项多中心II期研究目前正在进行中。
BackgroundIrinotecan (CPT-11) and bolus 5-fluorouracil (5-FU)/leucovorin (LV) administered weekly for 4 weeks every 42 days (Saltz regimen) is active but substantially toxic in patients with metastatic colorectal cancer (CRC). The efficacy and toxicity of this regimen, however, have not been determined in Japanese patients with metastatic CRC.MethodsWe investigated the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and recommended phase II dose (RD) for CPT-11 given i.v. (90-min infusion) and bolus 5-FU plus biologically activel-LV administered weekly for 3 weeks every 28 days (modified Saltz regimen) in Japanese patients with metastatic CRC. Eighteen patients with measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less, and adequate organ functions were enrolled.ResultsAt dose level 2 (CPT-11, 100 mg/m2; 5-FU, 400 mg/m2; andl-LV, 25 mg/body), 1 of 6 patients had DLT (febrile neutropenia). At dose level 3 (CPT-11, 100 mg/m2; 5-FU, 500 mg/m2; andl-LV, 25 mg/body), 2 of 6 patients had DLT (febrile neutropenia and grade 4 neutropenia lasting more than 4 days). To determine whether level 3 was the MTD level, an additional 3 patients were treated at this level, but no DLT was observed. Consequently, 2 of 9 patients had DLT at level 3, this level thus being considered as the RD. At this level, grade 3–4 neutropenia was common but manageable. Nonhematological toxicities were mild. Seven partial responses were observed in the 18 enrolled patients (response rate [RR], 39%), and 8 patients (44%) experienced stable disease.ConclusionThis CPT-11/5-FU/l-LV regimen administered weekly for 3 weeks every 28 days has substantial antitumor activity, with manageable toxicities. A multicenter phase II study is currently underway.