Epirubicin, Oxaliplatin and Fluorouracil (EOF) in Cancer of the Esophagus, Gastroesophageal Junction, or Stomach
RATIONALE: Drugs used in chemotherapy, such as epirubicin, oxaliplatin, fluorouracil, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy and radiation therapy after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This phase II trial is studying how well giving combination chemotherapy, surgery, and radiation therapy works in treating patients with locoregionally advanced cancer of the esophagus, gastroesophageal junction, or stomach.
Drug: epirubicin hydrochloride
Procedure: adjuvant therapy
Procedure: neoadjuvant therapy
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Trial of Induction Chemotherapy With Epirubicin, Oxaliplatin and Fluorouracil (EOF) Followed by Esophagogastrectomy and Post-operative Concurrent Chemoradiotherapy With Fluorouracil and Cisplatin, in Patients With Loco-regionally Advanced Adenocarcinoma of the Esophagus, Gastroesophageal Junction and Gastric Cardia|
- Feasibility of resectability rate [ Time Frame: 3 cycles ] [ Designated as safety issue: No ]
Prior experience at this institution suggests a resectability rate after induction chemoradiotherapy of 85-90%, primarily based on disease extent at the time of surgery. Resectability below 75% will suggest that this induction regimen is not feasible.
Similarly, prior experience suggests that post-operative chemoradiotherapy can be given to between 70-80% of resected patients. If adjuvant chemoradiotherapy cannot be given to at least 65% of the resected patients on this trial, the feasibility of this schedule will be in doubt.
- Response rate [ Time Frame: 3 cycles ] [ Designated as safety issue: No ]Experience with the EOF regimen in patients with advanced disease suggests a response rate of 40%. This is a difficult endpoint in patients with only loco-regional disease. A pathological response rate (pathologic downstaging compared to initial clinical stage) of less than 30% will suggest that this regimen is insufficiently active.
- Overall survival [ Time Frame: Duration of study ] [ Designated as safety issue: No ]A 3-year survival of less than 35% will suggest inefficacy of this treatment protocol. A survival rate greater than 50% would suggest efficacy and justify further study.
- Locoregional control and distant metastatic control [ Time Frame: 3 cycles ] [ Designated as safety issue: No ]A distant metastatic control rate of greater than 55 % would suggest efficacy for this treatment protocol. A locoregional control rate of less than 75% would suggest inefficacy.
- Toxicity [ Time Frame: Duration of study ] [ Designated as safety issue: Yes ]
|Study Start Date:||January 2008|
|Primary Completion Date:||June 2012 (Final data collection date for primary outcome measure)|
|Experimental: Epirubicin, Oxaliplatin and Fluorouracil||
20 mg/m2/day IV continuous infusion over 24 hours for 96 total hours.Drug: epirubicin hydrochloride
50 mg/m2 IV bolusDrug: fluorouracil
200 mg/m2/day will be given as a continuous intravenous infusion for all 9 weeks, beginning on day 1.Drug: oxaliplatin
130 mg/m2 IV infusion over 2 hoursProcedure: adjuvant therapy
Between 6-10 weeks after surgery patients will begin postoperative chemoradiotherapy. Daily radiation therapy fractions of 180-200 cGy will be given to the esophago-gastric bed and draining lymphatic regions to a total dose of 50-55 Gy (60 Gy in the event of an R1 or R2 resection). Concurrent with this radiation, two cycles of chemotherapy will be given, during the first and fourth weeks of the radiationProcedure: neoadjuvant therapy
Three weeks after discontinuing the fluorouracil (12 weeks after study entry) patients will be fully restaged to assess for a clinical response, and to ensure that there is no contraindication to surgical resection, which will be scheduled for approximately one week later (13 weeks after study entry).
Surgery will consist of a transthoracic esophagogastrectomy or a total gastrectomy with Roux-en-Y esophagojejunostomy depending on the location and extent of the tumor at surgery. An appropriate lymphadenectomy will be performed. Immediate reconstruction is anticipated if possible.
- To assess the feasibility and tolerability of induction chemotherapy comprising epirubicin hydrochloride, oxaliplatin, and fluorouracil (EOF), followed by surgical resection and postoperative concurrent chemoradiotherapy comprising fluorouracil and cisplatin in patients with locoregionally advanced adenocarcinoma of the esophagus, gastroesophageal junction, or gastric cardia.
- To determine the rate of complete and partial response to three courses of EOF induction chemotherapy.
- To compare the recurrence-free and overall survival of patients treated with this regimen vs historical controls at this institution.
- To compare patterns of failure in patients treated with this regimen vs historical controls at this institution.
- Induction chemotherapy: Patients receive epirubicin hydrochloride IV over 3-15 minutes and oxaliplatin IV over 2 hours on day 1 and fluorouracil IV continuously on days 1-21. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
- Surgery: Four weeks after completion of induction chemotherapy, patients with locoregionally confined disease (T0-4, N0-1, M0-1a) undergo transthoracic esophagogastrectomy or total gastrectomy with Roux-en-Y esophagojejunostomy, depending on the location and extent of the tumor at the time of surgery.
- Postoperative chemoradiotherapy: Beginning 6-10 weeks after surgery, patients undergo radiotherapy 5 days a week for approximately 6 weeks. Patients also receive fluorouracil IV continuously and cisplatin IV continuously over 96 hours in weeks 1 and 4 of radiotherapy.
After completion of study treatment, patients are followed every 8-12 weeks for 3 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00601705
|United States, Ohio|
|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44106-5065|
|Principal Investigator:||David J. Adelstein, MD||Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center|