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

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

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 (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 (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 (Celebrex)
with chemotherapy in the treatment of colorectal carcinoma.

Rangaswamy Govindarajan reports on a phase II trial of the combination of
irinotecan and 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 (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


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