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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.
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.
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.
Erlotinib was reported
and cisplatin alone.
Recently, the addition of docetaxel as a third agent to have a 10% response rate in adenocarcinoma of the GE junction,
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.
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.
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,
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
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.
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.
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.
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. ■
1. Jemal A, Siegel R, Ward E, et al., Cancer Statistics 2006, CA Cancer 11. Macdonald J, Smalley S, Benedetti J, et al., Chemoradiotherapy 19. Kang Y, Kang YK, Shin DB, et al., Randomized phase III trial of
J Clin, 2006;56:106–30. after surgery compared with surgery alone for adenocarcinoma of capecitabine/cisplatin (XP) vs. continuous infusion of
2. Kamangar F, Dores G, Anderson WF, Patterns of cancer incidence, the stomach or gastroesophageal junction, New Engl J Med, 5-FU/cisplatin (FP) as first-line therapy in patients (pts) with
mortality and prevalence across five continents: defining priorities 2001;345:725–30. advanced gastric cancer (AGC): efficacy and safety results, J Clin
to reduce cancer disparities in different geographic regions of the 12. Bedenne L, Michel P, Bouche O, et al., Chemo-radiation followed Oncol, 2006;24(18S):4018.
world, J Clin Oncol, 2006;24:2137–50. by surgery compared to chemo-radiation alone in locally advanced 20. Cunningham D, Rao S, Starling N, et al., Randomised multicentre
3. Lagergren J, Bergstrom R, Lindgren A, et al., Symptomatic operable thoracic oesophageal cancer: a randomized multicentric phase III study comparing capecitabine with fluorouracil and
Gastroesophageal Reflux As A Risk Factor for Esophageal phase III trial (FFCD 9102), J Clin Oncol, 2007;25(10):1160–68. oxaliplatin with cisplatin in patients with advanced
Adenocarcinoma, N Engl J Med, 1999;340:825–31. 13. Stahl M, Stuschke M, Lehmann N et al., Chemoradiation with or oesophagogastric (OG) cancer: The REAL 2 trial, J Clin Oncol,
4. Engel LS, Chow W, Vaughan TL, et al., Population attributable risks without surgery in patients with locally advanced squamous cell 2006;24(18S):4017.
of esophageal and gastric cancers, J Natl Cancer Inst, 2003;95: carcinoma of the esophagus, J Clin Oncol, 2005;23:2310–17. 21. Ajani JA, Lee FC, Deepti SA, et al., Multicenter Phase II Trial of S-1
1404–13. 14. Webb A, Cunningham D, Scarffe JH et al., A randomised trial Plus Cisplatin in Patients With Untreated Advanced Gastric or
5. Enzinger PC, Mayer RJ, Esophageal cancer, N Engl J Med, 2003; comparing ECF with FAMTX in advanced oesophago-gastric Gastroesophageal Junction Adenocarcinoma, J Clin Oncol, 2006;
349(23):2241–52. cancer, J Clin Oncol, 1997;15:261–7. 24:663–67.
6. Kelsen DP, Ginsberg R, Pajak TF, et al., Chemotherapy Followed by 15. Wagner AD, Grothe W, Lordick F, et al., Chemotherapy in 22. Shah MA, Ramanathan RA, Ilson DH, et al., Multicenter phase II
Surgery Compared with Surgery Alone for Localized Esophageal Advanced Gastric Cancer: A Systematic Review and Meta-Analysis trial of irinotecan, cisplatin, and Bevacizumab in patients with
Cancer, N Engl J Med, 1998;339:1979–84. Based on Aggregate Data, J Clin Oncol, 2006;24:2903–9. metastatic gastric or gastroesophageal junction adenocarcinoma,
7. Medical Research Council Esophageal Cancer Working Group, 16. Van Cutsem E, Moiseyenko VM, Sergei T, et al., Phase III Study of J Clin Oncol, 2006;24:5201–6.
Surgical resection with or without preoperative chemotherapy in Docetaxel and Cisplatin Plus Fluorouracil Compared With Cisplatin 23. Janmaat ML, Gallegos-Ruiz MI, Rodriguez JA, et al., Predictive
esophageal cancer: a randomized controlled trial, Lancet, 2002; and Fluorouracil As First-Line Therapy for Advanced Gastric factors for outcome in a phase II study of gefitinib in second line
359:1727–33. Cancer: A Report of the V325 Study Group, J Clin Oncol, 2006;24: treatment of advanced esophageal cancer patients, J Clin Oncol,
8. Cunningham D, Allum W, Stenning SP, et al., Perioperative 4991–7. 2006;24:1612–19.
chemotherapy versus surgery alone for resectable 17. Dank M, Zaluski J, Barone C, et al. Randomized phase 3 trial of 24. Dragovich T, McCoy S, LaFleur B, et al., Phase II trial of Erlotinib in
gastroesophageal cancer, N Engl J Med, 2006;355:11–20. irinotecan + 5FU/folinic acid vs CDDP + 5FU in first line advanced gastroesophageal junction and gastric adenocarcinoma, J Clin
9. Herskovic A, Martz LK, Al-Sarraf M, et al., Combined gastric cancer patients, Proc Amer Soc Clin Oncol, 2005;23:308 Oncol, 2006;24:4922–7.
chemotherapy and radiotherapy compared with radiotherapy (abstract 4003). 25. Tew W, Shah M, Schwartz G, et al., Phase II trial of erlotinib for
alone in patients with cancer of the esophagus, New Engl J Med, 18. Al-Batran S, Hartmann J, Probst S, et al., A randomized phase III second-line treatment in advanced esophageal cancer, 2005
1992;326:1593–8. trial in patients with advanced adenocarcinoma of the stomach Gastrointestinal Cancers Symposium ASCO, Abstract 5.
10. Tepper J, Krasna M, Niedwicki D, et al., Superiority of trimodality receiving first-line chemotherapy with fluorouracil, leucovorin and 26. Ott K, Weber WA, Lordick F, et al., Metabolic Imaging Predicts
therapy to surgery alone in esophageal cancer: Results of CALGB oxaliplatin (FLO) versus fluorouracil, leucovorin and cisplatin (FLP), Response, Survival, and Recurrence in Adenocarcinomas of the
9781, J Clin Oncol, 2006;24(Suppl. 18S):4012. J Clin Oncol, 2006;24(18S):4016. Esophagogastric Junction, J Clin Oncol, 2006;24:4692–8.
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