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chapter, the landmark studies in various settings of chemotherapy
for esophageal and gastric cancer would be reviewed with particu-
lar attention to relative benefits in the adenocarcinoma of esopha-
gus and esophagogastric junction. Table 1 summaries the landmark
chemotherapy studies in the curative setting.
The status of resection margin after surgical resection is impor-
tant when we consider chemotherapy. R0 is no cancerous cells seen
microscopically; R1 is cancerous cells can be seen microscopically;
R2 is cancer could be seen by macroscopic examination on the
resection margin.Chemotherapy alone has been evaluated in the preoperative setting
and in principle may downstage the tumor, facilitate R0 resection
and eradicate micrometastasis. The Intergroup 0113 study ran-
domized patients of both adenocarcinoma and squamous cell carci-
noma of the esophagus to three cycles of preoperative cisplatin and
5-fluorouracil (5FU) versus surgery alone [ 9 ]. Postoperative che-
motherapy was recommended in the patient who showed good
response to preoperative chemotherapy. Around half of the patients
had adenocarcinoma. Initial report did not show a significant sur-
vival benefit for preoperative chemotherapy although morbidity
and mortality did not appear to increase. The outcomes were simi-
lar in esophageal squamous cell and adenocarcinoma in the whole
group. Subsequent report of the study with long-term follow-up
again did not show a survival difference between the two arms [ 10 ].
Patients with R0 resection had a highly significant survival
advantage over those with R1, R2 or no resection. The 3-year sur-
vival for patients with R0 resection was 39% compared with 12%
and 4% for those with R1 and R2 resection, respectively. For
patients undergoing surgery alone, both locoregional and distant
failure were higher in patients with adenocarcinoma, as opposed to
those with squamous histology. On the other hand, adenocarci-
noma was associated with decreased risk of death in patients who
received preoperative chemotherapy.
Eight hundred and two patients with resectable esophageal
carcinoma were randomized to receive two cycles of preoperative
cisplatin and 5FU or immediate surgery in the Medical Research
Council (MRC) OE02 study [ 11 ]. Adenocarcinoma constituted
66% of the study population and preoperative radiotherapy was
allowed in both study arms. In contrast to the Intergroup 0113
study, preoperative chemotherapy significantly improved the over-
all survival from 13.3 to 16.8 months. No difference in the effect
of chemotherapy was observed with regard to histology, age, sex,
site, dysphagia, or performance status. In particular, the hazard
ratios for treatment effect were the same for both adenocarcinoma
and squamous histology. The report on long-term outcomes
showed a consistent improvement in 5-year survival and this is irre-
spective of histology subtypes [ 12 ].1.1 Chemotherapy
in Curative Setting
1.1.1 Preoperative
Chemotherapy
Ka-On Lam and Dora L. W. Kwong