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, inColorado Springs, Colorado. The purpose of these annual workshops is to reviewthe latest data on new agents, with a particular focus on the broadly used agentirinotecan (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 ideasand directions. The meetings were more like a workshop rather than didacticsessions. Six separate scientific sessions were held, and the respectivesessions covered colorectal carcinoma, upper gastrointestinal/genitourinarycarcinoma, lung carcinoma, and new combinations and other tumor types. Theseworkshops also were meant to develop enduring material for wider distribution tospecialists who did not attend.

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

In this volume, Jean-Yves Douillard et al review several randomized phase IIItrials that are ongoing in Europe and that assess the potential benefit of afluorouracil (5-FU)/leucovorin-irinotecan combination in the adjuvant settingfor patients with stage II or III colorectal cancer. Recent combinations ofchemotherapy, such as the currently recommended first-line treatment consistingof 5-FU plus leucovorin and irinotecan, have improved the response rate andsurvival in patients with metastatic colorectal cancer significantly. Thisarticle reviews the inclusion criteria and goal of these European trials andprovides an update on accrual and on tolerance.

Cyclooxygenase-2 (COX-2) inhibitors have a proven role in preventingneoplastic disease, and a laboratory-based rationale supports their use incombination with chemotherapy in treating such established tumors as colorectalcancer. Charles Blanke discusses the potential role and mechanisms of COX-2inhibitors 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 ofirinotecan and thalidomide (Thalomid), a glutamic acid derivative withantiangiogenic properties, as second-line therapy in patients with metastaticcolorectal cancer. He presents preliminary response and safety data for 18enrolled patients. The response rate was 22% (4/18), with one complete responseand 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 andcapecitabine (Xeloda), an oral fluoropyrimidine. Preclinical data have shownthat the sequential administration of low-dose irinotecan plus capecitabine ishighly curative in in vivo xenograft models of human colorectal cancer. Dr. Kerrconcludes that irinotecan/capecitabine is an active combination with responserates of 40% to 60%; further, it is fairly well tolerated, limited byneutropenia and diarrhea. Future studies of this combination would be ofinterest.

Lee Ellis et al conclude volume 1 with a review of tumor angiogenesis, with afocus on the angiopoietins (Ang) -1 and -2 that mediate endothelial cellstability and that are involved in the priming of endothelial cells for responseto mitogenic stimuli. Thus, a novel antiangiogenic strategy may be one thatleads to enhanced endothelial cell stability, thereby protecting endothelialcells from standard angiogenic stimuli. This may lead to tumor dormancy bytransforming a rapidly growing tumor into an indolent tumor. Dr. Ellis’ groupalso reviews data from experimental studies that support the hypothesis that theimbalance of Ang-2 activity over Ang-1 activity is important in the angiogenicprocess and may be an initiating factor in angiogenesis.

In conclusion, I believe that the data presented at The University of Texas M. D. Anderson Cancer Center Investigators’ Workshop provided currentinsights, trends, and practices in relevant areas of oncology. I hope you willfind the information in this and future volumes useful in designing newinvestigations, in educating your colleagues, and in contributing to the bettermanagement of all patients.