RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as oxaliplatin, fluorouracil, leucovorin, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with radiation therapy may kill more tumor cells. PURPOSE: This randomized phase II/III trial is studying radiation therapy and two different combination chemotherapy regimens to compare how well they work as first-line therapy in treating patients with esophageal cancer that cannot be removed by surgery.
OBJECTIVES: Primary * To assess the feasibility of radiochemotherapy comprising oxaliplatin, fluorouracil, and leucovorin calcium (FOLFOX regimen) vs fluorouracil and cisplatin (Herskovic regimen) in patients with inoperable esophageal cancer. (Phase II) * To assess the endoscopic complete response rate in patients treated with these regimens. (Phase II) * To compare the event-free survival of patients treated with these regimens. (Phase III) Secondary * To assess the toxicity profile of these regimens using the NCI CTC v2.0 criteria. (Phase II) * To compare the overall survival, endoscopic complete response rate, incidence of grade 3-4 toxicities, and time to treatment failure in patients treated with these regimens. (Phase III) * To evaluate the quality of life of these patients using EORTC QLQ-C30 (version 3) and a validated disease-specific module EORTC QLQ-OES18. (Phase III) OUTLINE: This is a multicenter study. Patients are stratified according to histological type (adenocarcinoma or adenosquamous carcinoma vs squamous cell carcinoma), pretreatment weight loss within the past 6 months (grade 1 \[\< 10%\] vs grade 2 \[≥ 10%\]), ECOG performance status (0 vs 1 vs 2), and participating center. Patients are randomized to 1 of 2 treatment arms. * Arm I (modified FOLFOX 4 regimen): Patients undergo radiotherapy 5 days a week for 5 weeks. Beginning concurrently with radiotherapy, patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment with chemotherapy repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. * Arm II (Herskovic regimen): Patients undergo radiotherapy as in arm I. Patients also receive cisplatin IV continuously over 24 hours on day 1 and fluorouracil IV continuously over 96 hours on days 1-4 of weeks 1, 5, 8, and 11 in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, periodically during study therapy, and then every 6 months for 1 year and annually for 3 years after completion of study therapy. After completion of study therapy, patients are followed at 4 weeks and then every 3-6 months until disease progression. PROJECTED ACCRUAL: A total of 97 patients will be accrued for the phase II portion of the study. A total of 169 patients will be accrued for the phase III portion of the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
266
CHR de Besancon - Hopital Saint-Jacques
Besançon, France
Hopital Saint Andre
Bordeaux, France
Institut Bergonie
Bordeaux, France
Hopital Ambroise Pare
Boulogne-Billancourt, France
Polyclinique Du Parc
Caen, France
Centre Regional Francois Baclesse
Caen, France
Hopital Du Bocage
Dijon, France
Centre de Lutte Contre le Cancer Georges-Francois Leclerc
Dijon, France
Centre Oscar Lambret
Lille, France
Centre Hospital Regional Universitaire de Limoges
Limoges, France
...and 18 more locations
Percentage of patients who complete the full study treatment (Phase II)
Time frame: 12 weeks
Endoscopic complete response rate (Phase II)
Time frame: 12 weeks
Progression-free survival (Phase III)
Time frame: Until progression
Safety profile as assessed by NCI CTC v2.0 (Phase II)
Time frame: Total duration of the trial
Overall survival (Phase III)
Time frame: Total duration of the trial
Complete response rate (Phase III)
Time frame: Total duration of the trial
Time to treatment failure (Phase III)
Time frame: Total duration of the trial
Incidence of grade 3-4 toxicities (Phase III)
Time frame: Total duration of the trial
Quality of life as assessed by EORTC QLQ-C30 (version 3) and EORTC QLQ-OES18 (Phase III)
Time frame: Total duration of the trial
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