Henry C. Pitot, MD

Metastatic well or moderately differentiated neuroendocrine tumors of the gastrointestinal tract and lung (NETs) are a fascinating and markedly heterogeneous group of generally indolent, but relentless cancers.

The current recommendation for adjuvant chemotherapy for patients with newly diagnosed stage III colon cancer involves 6 months of fluorouracil (5-FU) plus low- or high-dose leucovorin. In clinical trials performed throughout

The article by Damjanov and Meropol elegantly outlines the rationale behind the preclinical development of several potential new oral chemotherapy options for patients with advanced colorectal carcinoma and the available data from clinical trials in advanced colorectal cancer that evaluated the activity and safety of these agents. The authors relate the history of fluorinated pyrimidine therapy in colorectal cancer and the pharmacologic challenges to delivering effective oral therapy in a such a way that the chemistry behind the processes becomes readily intelligible. They note that the erratic absorption and blood levels associated with orally administered fluorouracil (5-FU) led to the current approaches to oral therapy.

Phase I trials of irinotecan (CPT-11 [Camptosar]), conducted at Johns Hopkins and the University of Texas, San Antonio, demonstrated some activity in patients with refractory advanced cancer. Three pivotal phase II studies of