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Irinotecan and Other Agents in Lung Carcinoma

Irinotecan and Other Agents in Lung Carcinoma

The 4th 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 has been 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, thus allowing
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.

In addition to stimulating research, another purpose of these
workshops is to develop enduring material for wider distribution to
those who did not attend. Thus, four volumes have been published. This
fourth and final volume is devoted to lung carcinomas. The three
previous volumes focused on colorectal cancers, upper
gastrointestinal/genitourinary carcinomas, and new combinations and
other tumor types.

Treatment Options in Small-Cell and Non-Small-Cell Lung Cancer

In this volume, Hong-Gyun Wu and Hak Choy review
current treatment options for patients with non-small-cell lung cancer and small-cell
lung cancer, and note that the combination of chemotherapy and radiation therapy
has improved outcomes in patients with non-small-cell lung cancer. Phase I/II
studies have demonstrated the single-agent activity of irinotecan against advanced
non-small-cell lung cancer, similar to that reported for other new active agents
such as vinorelbine (Navelbine), gemcitabine (Gemzar), paclitaxel, and docetaxel
(Taxotere). The synergistic effect of irinotecan and cisplatin was also observed
in both in vitro and clinical studies, and phase I/II studies of thoracic radiation
therapy and concurrent irinotecan and cisplatin demonstrated encouraging response
and survival rates with acceptable toxicities.

Studies in small-cell lung cancer have demonstrated that concurrent
chemotherapy and radiation therapy is more efficacious than sequential
chemotherapy and radiation therapy, early thoracic radiotherapy is
better than late radiotherapy, and twice-daily radiation is more
beneficial than once-daily treatment. While the cisplatin/etoposide
combination is currently the standard chemotherapy regimen for patients
with limited-disease small-cell lung cancer, trials are needed to
explore the potential role of irinotecan in these patients.

Agents Targeting Specific Biologic Pathways

Although treatment of advanced non-small-cell lung cancer has improved with
the availability of new agents such as the taxanes, topoisomerase inhibitors,
vinorelbine, and gemcitabine, platinum-based combination therapy has appeared
to have reached a threshold of therapeutic effectiveness. Roy
Herbst
discusses the development of agents targeting specific biologic pathways
in tumor development. These agents include endothelial growth factor receptor
(EGFR) inhibitors (eg, monoclonal antibody trastuzumab [Herceptin]) and EGFR
tyrosine kinase inhibitors (eg, ZD1839 [Iressa] and OSI-774 [Tarceva]), angiogenesis
inhibitors (eg, matrix metalloproteinase inhibitors, vascular endothelial growth
factor (VEGF) inhibitors (eg, monoclonal antibody to VEGF), and signal transduction
inhibitors (eg, ISIS-3521, an antisense oligonucleotide to protein kinase C-a).

A number of these agents have entered advanced-phase clinical
investigation, and Dr. Herbst notes that targeted therapy will have
applications in combination with cytotoxic chemotherapy or radiation
therapy at all stages of treatment.

Topoisomerase I Inhibitor/Nonplatinum Combinations

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