Gefitinib in combination with 5-fluorouracil (5-FU)/folinic acid and irinotecan in patients with 5-FU/oxaliplatin-refractory colorectal cancer: A phase I/II study of the arbeitsgemeinschaft fur internistische onkologie (AIO)

被引:15
作者
Hofheinz, Ralf-Dieter
Kubicka, Stefan
Wollert, Joerg
Arnold, Dirk
Hochhaus, Andreas
机构
[1] Univ Heidelberg, Fak Klin Med Mannheim, Med Klin 3, Onkol Zentrum, D-68167 Mannheim, Germany
[2] Hannover Med Sch, Med Klin, Abt Gastroenterol Hepatol & Endokrinol, Hannover, Germany
[3] Univ Halle Wittenberg, Med Klin 4, D-4010 Halle, Germany
来源
ONKOLOGIE | 2006年 / 29卷 / 12期
关键词
colorectal cancer; 5-fluorouracil; gefitinib; irinotecan; phase I study;
D O I
10.1159/000096449
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor. It potentiates cytotoxic drug activity in human xenografts. This phase I/II dose-finding study evaluated gefitinib in combination with a 5-fluorouracil (5-FU)/folinic acid (FA)/irinotecan (FOLFIRI-AIO) regimen in patients with metastatic colorectal cancer. Patients and Methods: Patients received gefitinib 250 mg per day, and escalating doses of FOLFIRI-AIO i.v. (dose level (DL) 1: 1600/500/60 mg/m(2); DL2: 1600/500/80 mg/m(2); DL3: 2000/500/80 mg/m(2)) weekly x 6. Dose-limiting toxicity (DLT) was determined in patients who completed 1 cycle of therapy. Results: 13 patients were enrolled. 1 out of 6 patients on DL1 exhibited DLT (acute psychosis), and a total of 7 patients received DL2. Of those, 3 patients had DLT during cycle 1 (nausea/vomiting n = 2; diarrhea n = 1, fatigue n = 2). Recruitment was stopped at this DL because of the unfavorable toxicity profile observed during the first and subsequent treatment cycles (out of 7 patients: nausea/vomiting grade 3 n = 2, diarrhea grade 3 n = 2; fatigue n = 3). Only 1 patient showed a partial remission, and 2 patients experienced stabilization of disease. Conclusions: Dose escalation had to be stopped early because of gastrointestinal toxicity and fatigue. This treatment regimen did not seem advantageous with respect to efficacy in comparison with FOLFIRI-AIO alone.
引用
收藏
页码:563 / 567
页数:5
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