Ficorella C, Ricevuto E, Morelli M F, Morese R, Cannita K, Cianci G, Porzio G, Di Rocco Z C, De Galitiis F, De Tursi M, Tinari N, Iacobelli S, Marchetti P
Medical Oncology, Department of Experimental Medicine, University of L'Aquila,Coppito, L'Aquila 67100, Italy.
Oncol Rep. 2006 May;15(5):1345-50. doi: 10.3892/or.15.5.1345.
A dose-finding study was designed to determine the maximum tolerated dose (MTD) of a bimonthly 12-h (10:00 p.m to 10:00 a.m), timed flat infusion (TFI) of 5-fluorouracil (5-FU) plus irinotecan (CPT-11), without leucovorin (LV), for metastatic colorectal carcinoma (CRC). A total of 33 patients were treated. Seven dose levels included a fixed CPT-11 dose of 180 mg/m2 on days 1 and 15 (d(1,15)) and escalating doses of 5-FU 600-1200 mg/m2 on days 1-4 and 15-18 (d(1-4,15-18)). Dose-limiting toxicities (DLTs) were: grade 3-4 non-hematologic, grade 4 hematologic and any toxicity causing a more than a 2-week delay in treatment. The MTD was reached at the seventh dose level. DLTs were observed in 5/8 patients (63%): G3 diarrhea, 2 patients, associated with G3 mucositis in one instance; G4 neutropenia, 2 patients, associated with severe asthenia in 1 patient; G3 hand-foot syndrome, 1 patient. The recommended doses (RDs) were established at the sixth dose level: 5-FU, 1100 mg/m2/d(1-4,15-18); CPT-11 180 mg/m2/d(1,15) [5-FU and CPT-11 dose intensity (DI), 2200 and 90 mg/m2 per week (w), respectively]. At the recommended dose, the DLTs in 38 cycles were: mucositis, 2 cycles (5%); afebrile G4 neutropenia and hand-foot syndrome, 1 cycle (3%). In 24 assessable patients, the overall response rate was 37.5%. The present CPT-11/5-FU schedule is highly tolerable in an outpatient setting using the highest recommended 5-FU dose effective in advanced CRC.
一项剂量探索研究旨在确定每两个月一次、持续12小时（晚上10点至上午10点）定时匀速输注（TFI）5-氟尿嘧啶（5-FU）加伊立替康（CPT-11）且不加亚叶酸（LV）用于转移性结直肠癌（CRC）的最大耐受剂量（MTD）。共治疗了33例患者。七个剂量水平包括第1天和第15天（d(1,15)）固定的CPT-11剂量180 mg/m²，以及第1 - 4天和第15 - 18天（d(1 - 4,15 - 18)）递增的5-FU剂量600 - 1200 mg/m²。剂量限制毒性（DLT）为：3 - 4级非血液学毒性、4级血液学毒性以及任何导致治疗延迟超过2周的毒性。在第七个剂量水平达到了MTD。在5/8例患者（63%）中观察到DLT：3级腹泻2例，其中1例伴有3级粘膜炎；4级中性粒细胞减少2例，其中1例伴有严重乏力；3级手足综合征1例。推荐剂量（RD）确定为第六个剂量水平：5-FU，1100 mg/m²/d(1 - 4,15 - 18)；CPT-11 180 mg/m²/d(1,15) [5-FU和CPT-11的剂量强度（DI）分别为每周2200和90 mg/m²]。在推荐剂量下，38个周期中的DLT为：粘膜炎2个周期（5%）；无发热的4级中性粒细胞减少和手足综合征1个周期（3%）。在24例可评估患者中，总体缓解率为37.5%。目前的CPT-11/5-FU方案在门诊环境中使用晚期CRC中推荐的最高有效5-FU剂量时耐受性良好。
