Cancer Treatment Today

As compared with surgery alone, a North American Intergroup trial (INT 0116) demonstrated a clear survival benefit with the administration of a postoperative regimen of fluorouracil, leucovorin, and external beam radiation therapy, and these findings have made combined modality radiation and chemotherapy a standard of care in patients with resected gastric cancer. More recently, the British MRC Adjuvant Gastric Cancer Infusional Chemotherapy (MAGIC) study found that preoperative and postoperative administration of epirubicin, cisplatin, fluorouracil significantly improved survival beyond surgery alone. Thus, after decades of negative studies, two successful strategies in localized gastric cancer are available. The current Intergroup trial (Cancer and Leukemia Group B trial 80101) is assessing the role of a potentially more active postoperative chemoradiation regimen whereas the proposed MAGIC-2 study will examine the role of adding bevacizumab to perioperative chemotherapy.

The approach of postoperative chemoirradiation with 5Fu is standard at this time. NCCN lists post chemoradiation chemotherapy as an option with ECF (epirubicin, cisplatin FU), only when ECG was administered preop as well. The Canadian Guidelines are more restrictive: “There is insufficient evidence from randomized trials to recommend neoadjuvant chemotherapy, or neoadjuvant or adjuvant radiation therapy or immunotherapy, either alone or in combination, outside of a clinical trial.”

Thus, postoperative chemoradiation is standard with 5FU but postoperative chemotherapy, unless performed exactly as in the MAGI study is not. The adjuvant chemo in other forms, irrespective of the actual agents used should be considered experimental since the strategy it is actively in trials.

To round off this discussion, it is worth it to mention that the plenary session at ASCO 2012 has reported the phase III CLASSIC study of the Xeliri regimen without radiation as adjuvant therapy. The XELOX and observation arms (ITT populations of 520 and 515 patients, respectively) were well balanced for baseline characteristics. This study showed the superior efficacy of adjuvant XELOX vs observation alone following D2 gastrectomy. Although OS data are still immature, there is a trend towards superiority of XELOX. The presenters concluded that these data support the use of adjuvant XELOX for GC but NCCN ahs not yet incorporated this result. There remains as well uncertainty as to whether they are applicable to a non-Asian population.

in Japan, standard adjuvant treatment is single-agent postoperative chemotherapy with the oral fluoropyrimidine S-1 after D2 surgery based on results of the ACTS-GC trial but this drug is not FDA approved in the USA.

Gastrointestinal Cancer Disease Site Group. Earle CC, Maroun J, Zuraw L. Neoadjuvant or adjuvant therapy for resectable gastric cancer [full report]. Toronto (ON): Cancer Care Ontario (CCO); 2003 May 21 [online update]. 21 p. (Practice guideline; no. 2-14). [79 references]

NCCN.org – GAST-4, gasric cancer

Benefit of Adjuvant Chemotherapy for Resectable Gastric Cancer A Meta-analysis JAMA. 2010;303(17):1729-1737

Fuchs CS, Tepper JE, Niedzwiecke D, et al. Postoperative adjuvant chemoradiation for gastric or gastroesophageal junction (GEJ) adenocarcinoma using epirubicin, cisplatin, and infusional (CI) 5-FU (ECF) before and after CI 5-FU and radiotherapy (CRT) compared with bolus 5-FU/LV before and after CRT: Intergroup trial CALGB 80101 (abstract 4003). J Clin Oncol 2011; 29:256s.

Takaki Yoshikawa & Mitsuru Sasako Gastrointestinal cancer: Adjuvant chemotherapy after D2 gastrectomy for gastric cancer Nature Reviews Clinical Oncology 9, 192-194 (April 2012)