E. Strong (ed.). Gastric cancer. Principles and practice. Springer (2015)
Gastric cancer remains a significant worldwide health problem, with proximal gastric and GEJ tumors an emerging epidemic in Western countries.
In the past 15 years, phase III studies performed in the West have shown a clear benefit for additional therapy other than surgery. In the USA, the two validated strategies are perioperative chemotherapy (based on the MAGIC study) or postoperative chemoradiation (based on the Intergroup 116 study). Given the similar improvements in outcomes with both approaches (an approximate 10–15% improvement in OS), our preference is for perioperative chemotherapy.
This approach is based on the following assumptions: that patients who undergo upfront surgery are at risk for developing metastatic disease at an early interval; that gastric cancer is a moderately chemosensitive disease; that upfront chemotherapy might control micrometastatic disease; that the benefit of adjuvant radiation remains unclear in our patient population, where D2 lymph node dissections are standard and; that adjuvant chemotherapy following partial or total gastrectomy is potentially associated with poorer therapy tolerance and potentially a lesser ability to deliver all planned adjuvant therapy.
In comparison, the standard of care in East Asia is for upfront surgery and adjuvant chemotherapy, where 1 year of an oral fluoropyrimidine or 6 months of a fluoropyrimidine/platinum doublet result in the same 10–15% improvement over surgery alone. Given that the magnitude of the absolute benefit is nearly the same with all of these approaches on the basis of comparing across phase III studies, it would be relatively unlikely that either a perioperative or a postoperative approach would emerge as the clearly superior strategy.
Therefore, what may be more critical than the timing of chemotherapy is that patients at a minimum receive a fluoropyrimidine/platinum in the perioperative setting or a fluoropyrimidine in the adjuvant setting (based on the results of the studies above). Whether the addition of a platinum compound to a fluoropyrimidine in the postoperative setting or of radiation to either preor postoperative chemotherapy will further improve outcome will hopefully be elucidated in the next several years.
In addition, ongoing and planned studies, e.g., the MAGIC-B study which randomizes patients with resectable GEJ and gastric adenocarcinomas to perioperative chemotherapy with or without bevacizumab, an antibody against vascular endothelial growth factor, are incorporating robust correlative components, which may identify biomarkers that are prognostic or predictive of benefit from chemotherapy and/or targeted agents.
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