Irinotecan Plus Fluorouracil/Leucovorin for Metastatic Colorectal Cancer: A New Survival Standard

Author:

Saltz Leonard B.1,Douillard Jean-Yves2,Pirotta Nicoletta3,Alakl May4,Gruia Gabriela4,Awad Lucile4,Elfring Gary L.3,Locker Paula K.3,Miller Langdon L.3

Affiliation:

1. Memorial Sloan-Kettering Hospital, New York, New York, USA

2. Centre Rene Gauducheau, Nantes, France

3. Pharmacia Corporation, Peapack, New Jersey, USA

4. Aventis, SA, Antony, France

Abstract

Abstract Background. Irinotecan is a topoisomerase I inhibitor that prolongs survival in patients with colorectal cancer refractory to fluorouracil (5-FU) and leucovorin (LV). This demonstrated activity of irinotecan as effective second-line therapy for colorectal cancer led to evaluation of combination irinotecan/5-FU/LV as first-line therapy for patients with metastatic disease. The results of two prospective phase III randomized, controlled, multicenter, multinational clinical trials in patients with previously untreated metastatic colorectal cancer served as the basis for U.S. and European approval of irinotecan/5-FU/LV for this indication. An overview of the findings of these two pivotal studies provides insights regarding the application of this new combination in clinical practice. Methods. Patients were randomly assigned to receive 5-FU/LV, either alone, or with concurrent irinotecan. The study conducted primarily in North America (study 1), employed bolus 5-FU/LV schedules, while the study performed primarily in Europe (study 2), employed infusional 5-FU/LV regimens. Major endpoints included tumor response rate, time to tumor progression (TTP), overall survival, quality of life, and safety. Results. In study 1, the respective confirmed response rates for irinotecan/5-FU/LV versus 5-FU/LV were 39% and 21% (p < .001); median TTPs were 7.0 months and 4.3 months, respectively (p = .004). In study 2, response rates for irinotecan/5-FU/LV versus 5-FU/LV alone were 35% and 22% (p = .005); median TTPs were 6.7 months and 4.4 months, respectively (p < .001). Survival time increased significantly with irinotecan/5-FU/LV versus 5-FU/LV alone in both studies (study 1: median 14.8 months versus 12.6 months, p = .042; study 2: median 17.4 months versus 14.1 months, p = .032). The combined analysis of the data from the two studies showed median survivals of 15.9 months versus 13.3 months, favoring the irinotecan-containing combinations (stratified-by-study p = .003). Patients in study 1 had a 36% lower risk of tumor progression and a 20% lower risk of death with the irinotecan combination than with 5-FU/LV alone; comparable risk reduction values in study 2 were 42% and 23%. While grade 3 diarrhea and vomiting were more common with irinotecan/5-FU/LV, grade 4 neutropenia, neutropenic fever, and mucositis were less common with irinotecan/5-FU/LV than with the Mayo Clinic 5-FU/LV regimen. Conclusion. The combination of irinotecan/5-FU/LV is superior to 5-FU/LV alone as first-line therapy for patients with metastatic colorectal cancer, offering consistently improved tumor control and prolonged survival. Irinotecan-based combination therapy sets a new survival standard for the treatment of this life-threatening disease.

Funder

Pharmacia Corporation, Peapack, NJ

Aventis SA, Antony, France

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3