Novel chemotherapeutic agents for gastrointestinal cancers

Although 5-fluorouracil has been the most commonly prescribed chemotherapy agent in the treatment of patients with gastrointestinal malignancies, new agents discussed herein provide options for the treatment of patients with colorectal, gastric, and pancreas cancer. Irinotecan was recently approved for the treatment of patients with colorectal cancer refractory to 5-fluorouracil. It has also been evaluated in chemotherapy-naïve patients both alone and in combination with 5-fluorouracil plus leucovorin or with oxaliplatin. Evaluated primarily in patients with colorectal cancer, oxaliplatin, a novel platinum compound, is an active agent. In combination with 5-fluorouracil and leucovorin, oxaliplatin provides a higher response rate than 5-fluorouracil and leucovorin alone. Furthermore, when oxaliplatin was added to the same 5-fluorouracil-based regimen in which patients had disease progression, clinical activity was observed. Other agents discussed herein are raltitrexed and the oral fluorinated pyrimidines, including uracil:tegafur plus leucovorin, capecitabine, eniluracil plus oral 5-fluorouracil, and S-1. Gemcitabine has been demonstrated to be more effective than 5-fluorouracil in the alleviation of disease-specific symptoms in patients with advanced pancreatic cancer. Gemcitabine also confers a modest survival advantage. Combinations of these novel compounds are evaluated in gastrointestinal malignancies in the advanced disease setting and in adjuvant therapy programs.