6533b857fe1ef96bd12b43dc

RESEARCH PRODUCT

State of the art treatment for gastric cancer: future directions

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Abstract Surgery remains the primary curative treatment for gastric cancer although the last 40 years has witnessed the increased utilisation of chemotherapy. 5-Fluorouracil (5-FU or F), then more recently cisplatin (C) and their derivatives, have laid the foundations for the use of chemotherapy and their activity has been modulated by combination with other anti-cancer drugs such as epirubicin (E) or leucovorin (folinic acid, LV) to improve the outcome for patients with advanced gastric cancer. In the palliative setting, despite recent efforts to refine and develop cisplatin/5-FU-based combinations and explore their effectiveness in different settings and regimens, the response rate has remained at around 40% and the overall survival period has obstinately refused to rise above 7–8 months. However, the last few years have seen renewed impetus in the struggle against advanced gastric cancer, heralded by the introduction of a new wave of chemotherapy drugs, principally the taxanes and the topoisomerase inhibitor, irinotecan. Recent early phase studies of drug combinations that use these new agents are reporting objective response rates of about 70% and overall median survival periods in excess of 10 months. Importantly, these advances are being made without excessive toxicity. In the adjuvant setting, recent meta-analyses of adjuvant chemotherapy have suggested that systemic treatment may achieve a small, statistically significant reduction in the risk of death. Preliminary data from an ongoing large, prospective phase III study of post-operative chemo-radiotherapy (US Intergroup 0116) shows significantly improved disease-free and 5-year survival. However, as 54% of patients appear to have had suboptimal surgery the observed benefit may arise from compensating for inadequate dissection. In the MAGIC trial perioperative chemotherapy with ECF demonstrated a significant improvement in progression-free survival (hazard ratio 0.70, P=0.002) and a potential improvement in overall survival (hazard ratio 0.80, P=0.063). Ongoing studies in the adjuvant setting are evaluating the potential role of new active agents such as docetaxel and irinotecan. Despite the improvements in therapeutic outcome, there is still much work to do as complete response rates are disappointingly low, patients with poor performance scores do particularly badly and treatment-related toxicity remains an issue in what is a distressing disease.