A Nonrandomized Phase II Study: Feasibility and Outcome of Neo Adjuvant Chemotherapy With Oxaliplatin, Fluorodeoxyuridine (FUdR), Taxotere and Leucovorin in the Treatment of Previously Untreated Advanced Esophago-Gastric Carcinoma
- Determine whether neoadjuvant chemotherapy comprising oxaliplatin, floxuridine,
docetaxel, and leucovorin calcium improves the rate of pathologic complete response in
patients with previously untreated, resectable stage II or III adenocarcinoma of the
- Determine the progression-free and overall survival of patients treated with this
- Determine the clinical response rates (complete response and partial response) in
patients treated with this regimen.
- Evaluate thymidylate synthase (TS), mRNA gene expression, TS activity, and TS and mRNA
sequence, to determine the altered spots as related to drug resistance in these
- Evaluate the potential for genome-wide gene expression profiling to predict response to
therapy, recurrence, progression-free survival, overall survival, and drug sensitivity
and resistance in these patients.
- Define the role of 5' untranslated region (5'-UTR) on translation and drug resistance
in these patients.
- Evaluate, by bone marrow aspirate analysis and flow cytometry, the initial presence of
cancer cells in the marrow, and clearance of these cells after treatment with this
- Evaluate the safety of this regimen in these patients.
- Assess quality of life of patients during and after treatment with this regimen.
OUTLINE: This is a nonrandomized, open-label study.
Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and docetaxel IV over 30
minutes, floxuridine IV over 24 hours, and leucovorin calcium IV over 24 hours on days 1, 8,
and 15. Treatment repeats every 4 weeks for up to 2 courses in the absence of disease
progression or unacceptable toxicity.
Patients undergo surgery after completion of chemotherapy. Patients who achieve pathologic
complete response (pCR) receive no further chemotherapy. Patients who have not achieved a
pCR receive 2 courses of adjuvant chemotherapy (same regimen as the neoadjuvant
chemotherapy) beginning 3 weeks after surgery.
Patients undergo blood and tissue collection periodically for correlative studies. Samples
are analyzed for thymidylate synthase (TS), mRNA gene expression, TS activity, and TS and
mRNA sequence by bone marrow aspirate, flow cytometry, and quantitative reverse
transcriptase-polymerase chain reaction.
Quality of life will be assessed at baseline, after neoadjuvant chemotherapy, after adjuvant
therapy, and at the first 3-month follow-up visit.
After completion of study treatment, patients are followed every 3 months for 2 years, every
6 months for 3 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 34 patients will be accrued for this study.
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Pathologic Complete Response
No evidence of cellular residual cancerous cells as evidenced by tumor tissue samples taken via surgery at the end of neo-adjuvant chemotherapy.
8 - 16 weeks
Bach Ardalan, MD
University of Miami Sylvester Comprehensive Cancer Center
United States: Food and Drug Administration
|University of Miami Sylvester Comprehensive Cancer Center - Miami||Miami, Florida 33136|