Refining docetaxel-containing therapy for gastric cancer

Gastric cancer-the second most common cause of cancer-related deaths worldwide-is a global health problem. Most cases present at advanced stages and are incurable due to locally advanced or metastatic disease. Although advanced gastric cancer is relatively chemosensitive, a gold standard chemotherapy regimen has yet to emerge, and response rates are of short duration. Cisplatin and 5-fluorouracil (CF) have emerged as the backbone agents in treating this disease. The pivotal V325 trial demonstrated the efficacy benefit of adding docetaxel to CF (DCF). DCF, however, is associated with significant toxicity, making it less tolerable to patients. As a result, docetaxel-containing regimens have been extensively studied and improved upon to mitigate toxicity while maintaining efficacy. Various dosing and scheduling permutations of the original DCF regimen have emerged, and substitutions with other 5-fluorouraci and platinum analogs have been studied. In this review we highlight some of these studies using docetaxel-based regimens as well as new approaches using targeted therapy, including monoclonal antibodies and tyrosine kinase inhibitors. Continuing efforts to improve the efficacy and tolerability of docetaxel-based chemotherapy, combining pharmacokinetic parameters and pharmacogenetic correlates, will further assist in developing optimized regimens. Emerging data using targeted therapy and biologics in combination with chemotherapy are promising, but results of ongoing studies are required to establish the safety and efficacy of these regimens.