Review of capecitabine as oral treatment of gastric, gastroesophageal, and Esophageal cancers

Capecitabine is a novel, orally administered fluoropyrimidine carbamate that has been approved for adjuvant treatment in patients with Stage III colon cancer, first-line metastatic colorectal cancer, and metastatic breast cancer, both as a single agent (for patients who are resistant to paclitaxel and anthracyclines) and in combination with docetaxel (after failure on anthracycline-based therapy). Capecitabine is being investigated in Phase I and II trials for the treatment of gastric, gastroesophageal, and esophageal cancers, primarily in the first-line metastatic setting but also in the adjuvant setting. The MEDLINE data base was searched for English-language clinical trials that were published from 1996 through October 2005 along with relevant abstracts that were presented at the American Society of Clinical Oncology and at meetings of the European Cancer Conference and the European Society of Medical Oncology. The most frequently investigated combinations were capecitabine with docetaxel, paclitaxel, cisplatin, or oxaliplatin, and capecitabine also has been combined with irinotecan. These therapies have yielded efficacy data that compare favorably with data from Phase III trials of parenteral 5-fluorouracil (5-FU) in the first-line metastatic setting, and they mostly are well tolerated. Capecitabine, when combined in doses < 1250 mg/m(2) twice daily, consistently resulted in a lower frequency of Grade 3 or 4 toxic effects. Capecitabine, as a representative of oral fluoropymidine, is a promising agent in gastroesophageal cancers. Although some Phase III trials are completed, additional Phase III trials of capecitabine-based combinations that compare its efficacy and safety with parenteral 5-FU-based combinations, in both first-line metastatic and adjuvant settings, would be important.