The 5th University of Texas M. D. Anderson Cancer Center Investigators'
Workshop was held on July 24-28, 2002, in San Diego, California.
The purpose of these annual workshops has been to review the latest data on
new agents, with a particular focus on the broadly used agent irinotecan (CPT-11,
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. Seven separate scientific sessions were held, and the respective sessions
covered general areas in tumor research, colorectal carcinoma, upper gastrointestinal
cancer, lung carcinoma, chemoradiation, other tumor types, and future directions.
In addition to stimulating research, another purpose of these workshops is
developing enduring material for wider distribution to those who did not attend this
workshop. Thus, three publications were planned. Volume 1 (May 2003) previously
described new combinations and other tumor types, including glioma, breast
cancer, and gynecologic carcinomas, while volume 2 (July 2003) described lung
carcinomas. This final volume is devoted to upper gastrointestinal and colorectal
Irinotecan/Paclitaxel in Adenomas of the Gastroesophageal Junction
Adenocarcinomas of the gastroesophageal junction comprise adenocarcinomas
of the esophagus and gastric cardia. In this volume, J. Randolph Hecht and colleagues
discuss a phase II trial of irinotecan and paclitaxel in the treatment of
adenomas of the gastroesophageal junction. The preliminary results demonstrated
that the combination shows good tolerability and possesses promising activity, even
in previously treated patients
Phase I Study of Irinotecan and Gemcitabine: Toxicity and Dose
Weijing Sun and Daniel Haller report on a phase I study designed to test the
toxicity of the combination of irinotecan with fixed-dose-rate infusion of gemcitabine
(Gemzar), and to determine the dose of the combination for subsequent phase II
investigation. Preclinical and clinical data suggest additive or synergistic effects
when combining these agents, with few or no overlapping toxicities. It has been
suggested that the fixed-dose-rate infusion of gemcitabine increases the concentration
of intracellular triphosphate gemcitabine, which may result in more objective
responses and longer median survival compared to the standard infusion.
Combined-Modality Therapy in Resectable Carcinoma
of the Esophagus or Gastroesophageal Junction
The prognosis of patients with local-regional carcinoma of the esophagus is
grim, and while preoperative chemoradiotherapy increases the fraction of patients
who achieve a pathologic complete response, that fraction is only 25%. In an
attempt to increase this percentage, my colleagues and I conducted a study of
combined-modality therapy in resectable carcinoma of the esophagus or gastroesophageal
junction. The trial used a combination of irinotecan and cisplatin that
possesses activity in patients with carcinoma of the esophagus, and also included
a regimen of continuous infusion fluorouracil (5-FU) and paclitaxel with radiotherapy;
surgery was performed for patients who completed chemotherapy and
had no evidence of metastatic disease. The trial objectives were to increase both
the R0 (curative) resection rate and the fraction of patients who have significant
pathologic response, and to evaluate morbidity and mortality.
Irinotecan and Gemcitabine in Advanced or Metastatic Biliary Cancer
Because irinotecan and gemcitabine possess good single-agent activity in
biliary tract cancers and may possess synergistic activity at clinically relevant
doses, this combination may represent a new option in the treatment of biliary
tract cancer. Pankaj Bhargava and colleagues describe the results from a phase II
study of gemcitabine and irinotecan in patients with advanced or metastatic biliary
cancer, and present data showing that the combination possesses moderate activity
and is well tolerated in patients with advanced or metastatic biliary cancer.
Irinotecan and Docetaxel in Metastatic or Recurrent
The outcomes for patients with metastatic or recurrent esophageal cancer are
dismal, with 1-year survival rates of approximately 20%. Ramaswamy Govindan
and his coworkers present data from a phase II study examining the combination
of docetaxel (Taxotere) and irinotecan in patients with metastatic or recurrent
esophageal cancer. The combination resulted in a response rate of 30%, with
median survival of 130 days. However, modifications to reduce the incidence of
febrile neutropenia need to be undertaken.
Role of Irinotecan in Esophageal Cancer
David Ilson and Bruce Minsky review the role of irinotecan in esophageal
cancer. Phase II evaluation of weekly irinotecan and cisplatin has shown encouraging
response rates in esophageal and gastric cancer. Novel regimens include the
combination of irinotecan with mitomycin (Mutamycin), the taxanes, and continuous
infusion 5-FU. Trials have also evaluated the combination of irinotecan with
concurrent radiotherapy. Phase II evaluation weekly irinotecan, cisplatin, and
concurrent radiotherapy as preoperative therapy in locally advanced esophageal
cancer is planned at single institutions and in cooperative group trials, as is further
phase I and II investigation of this regimen with the addition of targeted agents, ie,
celecoxib (Celebrex), cetuximab (Erbitux), and bevacizumab (Avastin). Alter-
native combinations of irinotecan with radiotherapy, including the addition of
docetaxel and continuous infusion 5-FU, are also undergoing evaluation.
Phase II Study of IFL in Advanced Colorectal Cancer
Jimmy Hwang and colleagues conclude the volume with a report of a phase II
study in advanced colorectal cancer with irinotecan, 5-FU, and leucovorin (IFL).
Irinotecan possesses antitumor efficacy both as a single agent, and incorporated
into the IFL regimen. Randomized studies confirmed the superiority of IFL over 5-
FU and leucovorin alone based on objective response, survival, and time to progression.
To improve the tolerability of IFL, some investigators have advocated
modifying the standard "Saltz regimen" to weekly for 2 weeks, with repeated
cycles every 21 days.
Therapy was well tolerated in the 23 patients treated, with a high median
relative dose intensity of irinotecan administered in the first 18. These data support
the hypothesis that modifying the schedule of IFL administration improves its
therapeutic index. If confirmed by randomized studies, this regimen may provide a
backbone for use in further investigation of new agents and combinations in the
treatment of advanced colorectal cancer.
In conclusion, I believe that the data presented at the University of Texas M. D.
Anderson Cancer Center Investigators' Workshop provided new insights and perspectives,
trends, and practices in various areas of oncology. I hope the reader will
find the information in this volume relevant, stimulating, and useful in designing