29p = 0.008) although the progression-free survival and overall sur-
vival were similar. FOLFIRI also demonstrated a superior toxicity
profile with respect to both hematologic and non-hematologic
adverse events [ 46 ]. Evidence for platinum-free regimens in the
palliative setting is compelling and improved tolerability has been
shown consistently. Consideration of such regimens should be
given in particular to patients who are contraindicated or intoler-
ant to platinum-based regimens.Patients with advanced disease are weak and often have impaired
organ functions, creating a big hurdle for patient recruitment in
optimally powered clinical study. So far, there are two phase III
randomized studies that compared chemotherapy with best sup-
portive care in the second-line that also included patients with
adenocarcinoma of the lower esophagus and esophagogastric
junction. The AIO study randomized patients to irinotecan vs. best
supportive care (BSC) but was closed prematurely due to poor
accrual [ 47 ]. There was no treatment response observed but more
than half of the patient achieved stable disease and patients were
more like to experience improvement in tumor-related symptoms
(50% vs. 7%). Despite small number of patients involved in the
study (n = 40), a significant improvement in overall survival was
observed (4.0 months vs. 2.4 months, p = 0.012). The second
study is the COUGAR-02 study compared 3-weekly docetaxel
with BSC in 168 patients [ 48 ]. Docetaxel was associated with
higher incidence of grade 3–4 toxicities as expected. More impor-
tantly, it does not only show benefit in symptom control and
disease- specific quality of life but it also prolongs the median sur-
vival of patients by 1.6 months (5.2 months vs. 3.6 months, HR
0.67, 95% CI 0.49–0.92; p = 0.01). The two studies were included
in the patient-level meta-analysis of 410 patients from three ran-
domized studies [ 49 ]. A third study from Korea was included that
compared irinotecan or docetaxel with BSC in second-line or
beyond setting in patients with gastric carcinoma only [ 50 ].
Nevertheless, the meta-analysis can still be viewed as a strong evi-
dence to support the use of chemotherapy in late-line setting.
Altogether 301 patients with gastric carcinoma, 76 with gastro-
esophageal, and 33 with esophageal adenocarcinoma were ana-
lyzed. Chemotherapy reduced the risk of death by 37% and similar
magnitude of benefit was seen with both docetaxel and irinotecan.
More recently, emerging evidence supported the addition of target
therapy in this setting.
To conclude, chemotherapy for the treatment of esophageal
and esophagogastric junction carcinoma continues to evolve but
high-level evidence is still an unmet need for this distinct entity
that only constitutes a small subgroup in most clinical studies.
Platinum-based combination chemotherapy remains the standard
of care in both curative and palliative setting. Chemotherapeutic1.2.2 Second-Line or
Beyond Treatment
Chemotherapy