Pemetrexed in patients with gastrointestinal carcinoma

Gastrointestinal tumors are among the most common cancers in the world. Palliative chemotherapy is widely used to treat patients with advanced or metastatic disease. The mainstay of chemotherapy for colorectal cancer is 5-fluorouracil (5-FU) modulated by leucovorin (LV), alone or in combination with oxaliplatin or irinotecan (CPT-11). Gemcitabine is currently the standard of care in patients with pancreatic cancer. There is no standard in gastric cancer, although cisplatin, 5-FU, and the anthracyclines are the most common drugs used. Pemetrexed, a new-generation antifolate antimetabolite, has demonstrated a 15% to 17% response rate in metastatic colorectal cancer, similar to those of other single agents in previously untreated patients. In patients with advanced pancreatic cancer, pemetrexed achieved a 6% response rate and a 28% 1-year survival rate, which is comparable to single-agent gemcitabine. Preliminary results in gastric cancer are encouraging. The generally mild side effect profile of pemetrexed, especially with folate supplementation and dexamethasone premedication, and the synergy between pemetrexed and drugs frequently used in gastrointestinal cancers, such as irinotecan, oxaliplatin, and gemcitabine, suggest that further clinical studies are indicated to determine the role of pemetrexed in the treatment of colorectal, pancreatic, and gastric cancers.