24
Another FNCLCC/ FFCD study also demonstrated superiority
of perioperative chemotherapy over surgery alone in terms of over-
all survival, disease-free survival, and curative resection rate [ 17 ].
Although treatment-related toxicity was more frequent with peri-
operative chemotherapy, postoperative morbidity was similar in
both arms. Of note, 64% of the randomized patients had tumor at
the gastroesophageal junction and 11% had tumor in the lower
esophagus. Thus, the result will be more relevant for the manage-
ment of adenocarcinoma of lower esophagus and esophagogastric
junction than the MRC MAGIC study in which this group of
patients was the minority (26%). Perioperative chemotherapy and
tumor location were significant prognostic factors for overall sur-
vival. Chemotherapy effect was more pronounced in the esopha-
gogastric junction subgroup, which represented around two-thirds
of the randomized patients.
Although both the MRC MAGIC study and the FNCLCC
tested the value of perioperative chemotherapy, the improvement
in clinical outcomes was likely contributed by the preoperative
parts as the completion rates for postoperative chemotherapy were
less than 50% in both studies. In addition, there is an ongoing
debate on the role of anthracycline in this setting. Recently the
FLOT regimen (2-weekly docetaxel, oxaliplatin, and infusion
5FU) was compared with the MRC MAGIC regimen in the phase
II/III randomized FLOT4-AIO study [ 18 ]. In the preliminary
report, FLOT increased the rate of pathologic complete response
by 10%. The compliance and side effect profile of FLOT was also
comparable with that of the MRC MAGIC regimen. The full
report with survival outcomes may provide early evidence to sup-
port triplet regimen in this setting.Compared to perioperative chemotherapy, there is less definitive
evidence to support the role of adjuvant therapy in adenocarci-
noma of the lower esophagus and esophagogastric junction. The
Intergroup 0116 study randomized patients to surgery with or
without postoperative chemoradiotherapy and showed a signifi-
cant improvement in survival [ 19 , 20 ]. However, only 20% of the
patients had adenocarcinoma of the esophagogastric junction and
adenocarcinoma of the lower esophagus was not included. The
trial was also criticized for suboptimal surgery and toxicity of the
regimen was a concern.
As opposed to the Western countries, the practice of adjuvant
chemotherapy is popular in Asia. Two large phase III randomized
controlled studies have defined the standard of care with surgery
followed by adjuvant chemotherapy in gastric cancer patients after
R0 resection and extended lymph node dissection. One year of
adjuvant S-1 in the ACTS GC study [ 21 , 22 ] and 6 months of
adjuvant XELOX in the CLASSIC study [ 23 , 24 ] both demon-
strated improvement of survival that persist with long-term follow-
up. It should be reminded that extrapolation of the study results to1.1.3 Postoperative
Chemotherapy
Ka-On Lam and Dora L. W. Kwong