Current status and future of chemotherapy and biochemotherapy in gastroesophageal cancers

Abstract

A number of advances recently have been made in the chemotherapeutic treatment of gastroesophageal cancer. Perioperative combination chemotherapy based on cisplatin and 5-fluorouracil (5-FU) improves the prognosis of patients with stage II and stage III disease. Preoperative initiation of chemotherapy seems to be essential for achieving this result, according to studies performed in the West. On the other hand, Japanese investigators demonstrated that postoperative administration of oral fluoropyrimidine prodrugs can substantially improve the prognosis of patients with curatively resected gastric cancer. The addition of docetaxel to cisplatin and 5-FU has significantly improved response rate, time to progression, and overall survival in patients treated for advanced gastric cancer, as well as prolonging time to definitive worsening of global health status and Karnofsky performance status. Due to increased hematologic toxicity with this regimen, particularly neutropenic infections, careful patient selection and optimal supportive care, including prophylactic granulocyte colonystimulating factor, are required. Alternative schedules are being investigated that could improve the tolerability of docetaxel plus platinum/fluoropyrimidine combination regimens. Further improvements in outcome may be achieved when even more active chemotherapy combinations including docetaxel are systematically implemented into the preoperative treatment of locally advanced gastroesophageal cancers. Initial results with biologic targeted agents in this setting are promising. Pathways currently under investigation include the epidermal growth factor receptors Her-1 and Her-2, vascular endothelial growth factor, and the epithelial cell adhesion molecule EpCAM. It is hoped that targeting these pathways will further increase the efficacy of biochemotherapy of gastroesophageal cancer. Evaluating early response to biochemotherapy using metabolic imaging is a novel approach that may allow for tailoring systemic therapy to individual tumor biology. A deeper understanding of the relevant pathognomonic molecular patterns and signatures in individual tumors may facilitate faster drug development and permit more accurate selection of active therapies in the future.