Irinotecan in Gastrointestinal Malignancies

The purpose of the annual investigators’workshops sponsored by The University of Texas M. D. Anderson Cancer Center hasbeen to review the latest data on new agents, with a particular focus on thebroadly used agent irinotecan (CPT-11, Camptosar). Investigators from around theworld are invited to present current research. The forums are highly interactiveand frank, thus allowing stimulation of new ideas and directions.

The 3^rd Investigators’ Workshop was held on July 13-16,2000, in St. Croix, US Virgin Islands. Five separate scientific sessions wereheld, covering:

colorectal carcinoma;

lung carcinoma;

breast carcinoma;

miscellaneous tumors including lymphomas; and

novel uses of topoisomerases including enhancement of radiation-induced cytotoxicity.

In addition to stimulating research, the workshops also fosterthe development of enduring material for wider distribution to those who did notattend this workshop. Three publications are intended as the result of this mostrecent workshop. This first volume is devoted to GI malignancies. Successivemonthly volumes will be devoted to breast malignancies (volume 2), and novelagents in lung and other malignancies (volume 3).

In This Issue: Insights and Trends

Leading off this volume, Daniel Haller provides an update onchemotherapy of advanced colorectal carcinoma and reviews the most currenttrials conducted in the United States and Europe. He concludes that not onlyhave new agents like irinotecan become part of the front-line therapy ofadvanced colorectal carcinoma, but oxaliplatin is also being widely used forthis purpose in some European countries. Dr. Haller emphasizes the potentialvalue of biomarkers for selecting specific and rational chemotherapy forcolorectal carcinoma.

Henry Pitot and Richard Goldberg discuss future directions inadjuvant therapy of stage III colon carcinoma. They note that future trials maydemonstrate that incorporating newer agents (irinotecan among them) may prove tobe the standard of care in the adjuvant setting. Both authors also state thatoral fluoropyrimidines have acceptable side effects and are being investigatedin the adjuvant setting.

Robert Diasio describes the current status of oral chemotherapyfor colorectal carcinoma. He reviews all of the current results withcapecitabine (Xeloda), uracil and tegafur (UFT) in conjunction with leucovorin(the combination known as Orzel), S-1, and BOF A-2. He also provides a succinctreview of the mechanism of action and various targets for these agents. Dr.Diasio concludes by stating that more oral agents are likely to be developed inthe future for this group of colorectal patients.

Jordan Berlin illuminates new directions in the treatment ofcolorectal carcinoma. His emphasis is on the development of novel therapies,such as immunotherapy (including monoclonal antibodies) and gene therapy, aswell as prospective investigation of new molecular targets that may affordbetter results.

New developments in the area of prevention of colorectalcarcinoma are reviewed by Patrick Lynch. He relates his own work with familialadenomatous polyposis (FAP) with the cyclooxygenase-2 (COX-2) inhibitor,celecoxib (Celebrex), demonstrating its ability to regress polyps. His extensivereview on this subject is supported by numerous references.

Eileen O’Reilly and David Ilson discuss their experience withthe combination of cisplatin (Platinol) and irinotecan in patients withesophageal carcinoma. Having demonstrated that it is an active combination, theyhave expanded their investigations by adding radiotherapy or anotherchemotherapeutic agent to this combination.

Jaffer Ajani and colleagues discuss their results with the samecombination of cisplatin and irinotecan in untreated patients who have advancedgastric carcinoma. The data suggest that it is an active combination, aspreviously reported by two Japanese groups.

Also presented are results of an ongoing randomized phase IIIstudy with a combination of gemcitabine (Gemzar) and irinotecan in patients withadvanced pancreatic carcinoma. Caio Rocha Lima and co-workers describe the studydesign and rationale for using this drug combination in patients with locallyadvanced or metastatic pancreatic cancer and no previous systemic therapy; thecontrol arm represents treatment with gemcitabine.

Tyvin Rich and Alexander Kirichenko discuss the schedule andtiming of the administration of irinotecan with radiotherapy. They make a casefor properly timing irinotecan when it is administered concurrently withradiotherapy, speculating that proper timing would not only increasecytotoxicity but reduce normal tissue toxic effects.

In conclusion, I believe that the data presented at TheUniversity of Texas M. D. Anderson Cancer Center Investigators’ Workshopaccurately presents current insights, trends, and practices in relevant areas ofoncology. I hope you will find this information useful in designing newinvestigations and educating your colleagues, in addition to contributing to thebetter management of patients.