Irinotecan in Gastrointestinal Malignancies

The purpose of the annual investigators’ workshops sponsored by The University of Texas M. D. Anderson Cancer Center has been 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 are invited to present current research. The forums are highly interactive and 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 were held, 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 foster the development of enduring material for wider distribution to those who did not attend this workshop. Three publications are intended as the result of this most recent workshop. This first volume is devoted to GI malignancies. Successive monthly volumes will be devoted to breast malignancies (volume 2), and novel agents in lung and other malignancies (volume 3).

In This Issue: Insights and Trends

Leading off this volume, Daniel Haller provides an update on chemotherapy of advanced colorectal carcinoma and reviews the most current trials conducted in the United States and Europe. He concludes that not only have new agents like irinotecan become part of the front-line therapy of advanced colorectal carcinoma, but oxaliplatin(Drug information on oxaliplatin) is also being widely used for this purpose in some European countries. Dr. Haller emphasizes the potential value of biomarkers for selecting specific and rational chemotherapy for colorectal carcinoma.

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

Robert Diasio describes the current status of oral chemotherapy for colorectal carcinoma. He reviews all of the current results with capecitabine(Drug information on capecitabine) (Xeloda), uracil and tegafur(Drug information on tegafur) (UFT) in conjunction with leucovorin (the combination known as Orzel), S-1, and BOF A-2. He also provides a succinct review 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 in the future for this group of colorectal patients.

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

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

Eileen O’Reilly and David Ilson discuss their experience with the combination of cisplatin(Drug information on cisplatin) (Platinol) and irinotecan in patients with esophageal carcinoma. Having demonstrated that it is an active combination, they have expanded their investigations by adding radiotherapy or another chemotherapeutic agent to this combination.

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

Also presented are results of an ongoing randomized phase III study with a combination of gemcitabine(Drug information on gemcitabine) (Gemzar) and irinotecan in patients with advanced pancreatic carcinoma. Caio Rocha Lima and co-workers describe the study design and rationale for using this drug combination in patients with locally advanced or metastatic pancreatic cancer and no previous systemic therapy; the control arm represents treatment with gemcitabine.

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

In conclusion, I believe that the data presented at The University of Texas M. D. Anderson Cancer Center Investigators’ Workshop accurately presents current insights, trends, and practices in relevant areas of oncology. I hope you will find this information useful in designing new investigations and educating your colleagues, in addition to contributing to the better management of patients.