Phase I study of 3-week schedule of irinotecan combined with cisplatin in patients with advanced solid tumors

被引:31
作者
de Jonge, MJA
Sparreboom, A
Planting, AST
van der Burg, MEL
de Boer-Dennert, MM
ter Steeg, J
Jacques, C
Verweij, J
机构
[1] Rotterdam Canc Inst, Daniel den Hoed Klin, Dept Med Oncol, NL-3075 EA Rotterdam, Netherlands
[2] Univ Rotterdam Hosp, Rotterdam, Netherlands
[3] Rhone Poulenc Rorer, Antony, France
关键词
D O I
10.1200/JCO.2000.18.1.187
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: To assess the feasibility, pharmacokinetic interaction, and possible sequence-dependent effects of the irinotecan/cisplatin combination given every 3 weeks, and to assess the influence of additional granulocyte colony-stimulating factor (G-CSF) on the hematalogic toxicity. Patients and Methods: Patients who had received no more than one prior combination chemotherapy regimen or two single-agent regimens were entered, Treatment consisted of a 90-minute irinotecan infusion followed by a 3-hour cisplatin infusion on day 1, with cycles repeated once every 3 weeks. After the maximum-tolerated dose was determined, the sequence of administration war; reversed. In a separate cohort of six patients, we assessed the effect of G-CSF on the experienced hematologic toxicity and dose-intensity. Irinotecan doses ranged from 175 to 300 mg/m(2) and cisplatin doses ranged from 60 to 80 mg/m(2). Results: Fifty-two patients entered the study; one was not eligible, and two were not assessable for response. Twenty-five patients were pretreated, and 26 were not. Fifty-one patients received a total of 223 courses. The dose-limiting toxicity was a combination of neutropenic fever, diarrhea, and fatigue at a dose level combining irinotecan 300 mg/m(2) with cisplatin 80 mg/m(2), Neutropenia was common (grades 3 to 4, 68%). Irinotecan pharmacokinetics were linear over the dose range studied. No sequence-dependent side effects were observed. Tumor responses included three complete responses and eight partial responses. Conclusion: For phase II studies, we recommend irinotecan 260 mg/m(2) combined with cisplatin 80 mg/m(2) once every 3 weeks for chemotherapy-naive patients in good physical condition, and irinotecan 200 mg/m(2) combined with cisplatin 80 mg/m(2) for other patients. (C) 2000 by American Society of Clinical Oncology.
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页码:187 / 194
页数:8
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