US_Gastro_Ilson.qxp 11/4/08 03:14 Page 42
Gastrointestinal Cancers
and squamous cell carcinoma of the esophagus. Phase III trials have irinotecan and cisplatin in advanced adenocarcinoma of the GE junction and
compared the addition of a third agent to cisplatin/5-FU versus cisplatin/ stomach.
22
An encouraging response rate of 65% and time to tumor
5-FU alone. The MRC developed the ECF regimen, which is a combination progression of 7.8 months was observed.
of epirubicin and cisplatin every three weeks in combination with daily
protracted continuous infusion 5-FU in esophageal and gastric cancer.
14
A Phase II trials of the tyrosine kinase inhibitors of the eGFR, including the
recently reported meta-analysis indicated that the addition of an agents erlotinib and gefitinib, have been recently reported. Gefitinib
anthracyline to 5-FU and cisplatin resulted in a modest one-month achieved only a 3% response rate in esophageal cancer, with a greater
improvement in survival in gastric adenocarcinoma compared with 5-FU degree of response seen with squamous cancers.
23
Erlotinib was reported
and cisplatin alone.
15
Recently, the addition of docetaxel as a third agent to have a 10% response rate in adenocarcinoma of the GE junction,
24
but
added to 5-FU and cisplatin was also shown to improve antitumor a single-institution trial of erlotinib reported no activity in esophageal or
response rates by 10%, time to tumor progression by nearly two months, GE-junction adenocarcinoma.
25
The combination of eGFR-targeted
and median survival by less than one month, at the cost of significant antibodies, including cetuximab and matuzimab, have been combined
gastrointestinal and hematological toxicity.
16
with chemotherapy regimens such as folinic acid (leucovorin), 5-FU, and
irinotecan (FOLFIRI); folinic acid (leucovorin), 5-FU, and oxaliplatin
Other recent phase III trials have suggested a potential equivalence of 5-FU (Eloxatin
®
) (FOLFOX); and ECF in phase II trials, with promising antitumor
and cisplatin to the combination of irinotecan and infusional 5-FU,
17
the responses reported to date in abstracts only. A phase III trial of matuzimab
substitution of oxaliplatin for cisplatin, or capecitabine for infusional plus chemotherapy in GE adenocarcinoma has recently been completed in
5-FU.
18,19
Modifying the ECF regimen with the substitution of oxaliplatin, comparison with chemotherapy alone with epirubicin, capecitabine, and
capecitabine, or both also appeared to achieve equivalent outcome cisplatin, and a report of this trial is pending.
compared with ECF, although the regimen combining epirubicin with
oxaliplatin and capecitabine achieved the longest median survival.
20
Another Tailoring therapy more precisely to individuals is under investigation
promising oral 5-FU analog, S-1, is currently in phase III evaluation in in a number of trials, including PET-scan response assessment to
combination with cisplatin, compared with conventional 5-FU and cisplatin, pre-operative therapy, DNA array analysis to identify potential prognostic
in advanced GE adenocarcinoma.
21
and predictive genetic profiles, and pharmacogenetic profiling of
chemotherapy targets that may predict response and resistance to
Targeted Therapy chemotherapy. One recent trial in patients undergoing pre-operative
Promising molecular targeted therapies for esophageal cancer in phase II chemotherapy in esophageal cancer indicated that early response to
and III clinical trials include monoclonal antibodies that target the VEGF induction chemotherapy identified on PET scan correlated with improved
ligand and signal transduction/tyrosine kinase inhibitors and monoclonal survival.
26
PET non-responders could be identified early, and potentially
antibodies that target eGFR. Bevacizumab, the monoclonal antibody- referred directly to surgery rather than continuing on ineffective
targeting VEGF, was recently evaluated in combination with weekly pre-operative therapy. ■
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42 US GASTROENTEROLOGY
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