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ONCOLOGY. Vol. 16 No. 4 3
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Introduction 

Introduction to Irinotecan and Other Agents in Colorectal Cancer, Volume 1

By Jaffer A. Ajani, MD, Guest Editor
Department of Gastrointestinal Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

| April 1, 2002

The Fourth Investigators’ Workshop sponsored by The University of Texas M. D. Anderson Cancer Center was held on July 25-29, 2001, in Colorado Springs, Colorado. The purpose of these annual workshops is to review the latest data on new agents, with a particular focus on the broadly used agent irinotecan(Drug information on irinotecan) (CPT-11, Camptosar).

Investigators from around the world were invited to present current research. The forums were highly interactive and frank to allow stimulation of new ideas and directions. The meetings were more like a workshop rather than didactic sessions. Six separate scientific sessions were held, and the respective sessions covered colorectal carcinoma, upper gastrointestinal/genitourinary carcinoma, lung carcinoma, and new combinations and other tumor types. These workshops also were meant to develop enduring material for wider distribution to specialists who did not attend.

Thus, four publications based on the most recent workshop will be published in ONCOLOGY. This first volume is devoted to irinotecan and other agents used in the prevention and treatment of colorectal malignancies. Successive monthly volumes will be devoted to upper gastrointestinal/genitourinary malignancies (volume 2), new combinations and other malignancies (volume 3), and lung malignancies (volume 4).

In this volume, Jean-Yves Douillard et al review several randomized phase III trials that are ongoing in Europe and that assess the potential benefit of a fluorouracil(Drug information on fluorouracil) (5-FU)/leucovorin-irinotecan combination in the adjuvant setting for patients with stage II or III colorectal cancer. Recent combinations of chemotherapy, such as the currently recommended first-line treatment consisting of 5-FU plus leucovorin and irinotecan, have improved the response rate and survival in patients with metastatic colorectal cancer significantly. This article reviews the inclusion criteria and goal of these European trials and provides an update on accrual and on tolerance.

Cyclooxygenase-2 (COX-2) inhibitors have a proven role in preventing neoplastic disease, and a laboratory-based rationale supports their use in combination with chemotherapy in treating such established tumors as colorectal cancer. Charles Blanke discusses the potential role and mechanisms of COX-2 inhibitors and reviews trials using the selective COX-2 inhibitor celecoxib(Drug information on celecoxib) (Celebrex) with chemotherapy in the treatment of colorectal carcinoma.

Rangaswamy Govindarajan reports on a phase II trial of the combination of irinotecan and thalidomide(Drug information on thalidomide) (Thalomid), a glutamic acid derivative with antiangiogenic properties, as second-line therapy in patients with metastatic colorectal cancer. He presents preliminary response and safety data for 18 enrolled patients. The response rate was 22% (4/18), with one complete response and three partial responses. Grade 3/4 toxicity was noted in 6% of patients.

David Kerr reviews phase I/II trials of the combination of irinotecan and capecitabine(Drug information on capecitabine) (Xeloda), an oral fluoropyrimidine. Preclinical data have shown that the sequential administration of low-dose irinotecan plus capecitabine is highly curative in in vivo xenograft models of human colorectal cancer. Dr. Kerr concludes that irinotecan/capecitabine is an active combination with response rates of 40% to 60%; further, it is fairly well tolerated, limited by neutropenia and diarrhea. Future studies of this combination would be of interest.

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