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World J Gastroenterol. Apr 28, 2014; 20(16): 4516-4525
Published online Apr 28, 2014. doi: 10.3748/wjg.v20.i16.4516
Adjuvant chemotherapy for gastric cancer: Current evidence and future challenges
Rosalba Miceli, Gianluca Tomasello, Giacomo Bregni, Maria Di Bartolomeo, Filippo Pietrantonio
Rosalba Miceli, Unit of Medical Statistics, Biometry and Bioinformatics, Fondazione IRCCS Istituto Nazionale Tumori, 20133 Milan, Italy
Gianluca Tomasello, Medical Oncology Division, Azienda Istituti Ospitalieri di Cremona, 26100 Cremona, Italy
Giacomo Bregni, Maria Di Bartolomeo, Filippo Pietrantonio, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Tumori, 20133 Milan, Italy
Author contributions: All authors gave substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; drafting the article and critical review for important intellectual content; and final approval of the version to be published.
Correspondence to: Rosalba Miceli, PhD, Unit of Medical Statistics, Biometry and Bioinformatics, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milan, Italy. rosalba.miceli@istitutotumori.mi.it
Telephone: +39-22-3903198 Fax: +39-22-3902095
Received: November 15, 2013
Revised: January 9, 2014
Accepted: January 19, 2014
Published online: April 28, 2014
Processing time: 165 Days and 7.7 Hours
Abstract

Gastric cancer still represents one of the major causes of cancer mortality worldwide. Patients survival is mainly related to stage, with a high proportion of patients with metastatic disease at presentation. Thus, the cure rate largely depend upon surgical resection. Despite the additional, albeit small, benefit of adjuvant chemotherapy has been clearly demonstrated, no general consensus has been reached on the best treatment option. Moreover, the narrow therapeutic index of adjuvant chemotherapy (i.e., limited survival benefit with considerable toxicity) requires a careful assessment of expected risks and benefits for individual patients. Treatment choices vary widely based on the different geographic areas, with chemotherapy alone more often preferred in Europe or Asia and chemoradiotherapy in the United States. In the present review we discuss the current evidence and future challenges regarding adjuvant chemotherapy in curatively resected gastric cancer with particular emphasis on the recently completed landmark studies and meta-analyses. The most recent patient-level meta-analysis demonstrated the benefit of adjuvant chemotherapy over curative surgery; the same Authors also showed that disease-free survival may be used as a surrogate end-point for overall survival. We finally discuss future research issues such as the need of economic evaluations, development of prognostic or predictive biomarkers, and the unmet clinical need of trials comparing perioperative chemotherapy with adjuvant treatment.

Keywords: Gastric cancer; Adjuvant chemotherapy; Radiotherapy; Randomized trial

Core tip: Despite the benefit of adjuvant therapy has been clearly demonstrated, no general consensus has been still reached on the best treatment option. The narrow therapeutic index of adjuvant chemotherapy requires a careful assessment of expected risks and benefits for individual patients. Many issues, such as the role of postoperative radiotherapy and the best chemotherapy regimen, are still under investigation. Moreover, no prognostic or predictive factors beyond pathological stage have been prospectively validated. Despite researchers’ efforts, this issue still represent an unmet medical need. In this review we describe the recently completed landmark studies and meta analyses, and we discuss the future challenges in this research field.