A new paradigm of chemotherapy for gastric cancer: speeding up, and more clinical trials to catch up

Abstract

tarium of useful agents and to accelerate the process of evaluating new treatment modalities. But what type of novel treatment modalities should we examine? And how can we make up for the delay in establishing gastric cancer treatment modalities, compared with those for other major solid tumors, without going by a roundabout way that was not successful a decade ago [7]? Paclitaxel, which has been heralded as a unique cytotoxic agent, could be one of the most promising novel chemotherapeutic agents for gastric cancer. To understand the effect of paclitaxel, a review of its basic and clinical pharmacology is necessary. Paclitaxel is a novel diterpenoid that contains a complex ring system, called a taxane ring, coupled with a complex ester chain. This taxane derivative is a member of the tubulin-binding agent class. But, unlike other agents in the tubulinbinding family that promote microtubule disassembly, paclitaxel shifts the equilibrium toward microtubule assembly, and stabilizes microtubules by preventing depolymerization [8,9]. Experimental studies have shown that paclitaxel has multiple biological activities, and different mechanisms of action are speculated depending on the concentration of paclitaxel. At a higher dose, paclitaxel blocks dividing cells in the G2/M phase, inhibits microtubular depolymerization, and directly kills tumor cells. At a lower concentration, paclitaxel induces apoptosis [10,11] anti-angiogenesis, and immunomodulation. Paclitaxel has already been used extensively in clinical practice, as one of the key drugs for the treatment of ovarian cancer, breast cancer, and lung cancer. As paclitaxel possesses a totally different mechanism of action compared with that of the fluoropyrimidines, the drug may bring about considerable improvements in the treatment of gastric cancer. The safety profile of paclitaxel has been well established. The incidence of severe hypersensitivity reactions observed in the initial clinical trials has been significantly reduced by the prophylactic administration of antiallergy medication, including a corticosteroid  2002 by International and Japanese Gastric Cancer Associations