Gemcitabine and Oxaliplatin Followed By Radiation Therapy, Fluorouracil, and Oxaliplatin in Treating Patients With Locally Advanced Pancreatic Cancer That Cannot Be Removed By Surgery

Gemcitabine and Oxaliplatin Followed By Radiation Therapy, Fluorouracil, and Oxaliplatin in Treating Patients With Locally Advanced Pancreatic Cancer That Cannot Be Removed By Surgery

Protocole de Phase II: Etude de Faisabilite de L'Oxaliplatine en Association Chimio-Radiotherapie Concomitante Dans le Traitement Des Cancers du Pancreas Localement Avances Non Resecables

RATIONALE: Drugs used in chemotherapy, such as gemcitabine, oxaliplatin, and fluorouracil, 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 together with radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving gemcitabine together with oxaliplatin followed by radiation therapy, fluorouracil, and oxaliplatin works in treating patients with locally advanced pancreatic cancer that cannot be removed by surgery.

OBJECTIVES: Primary Compare progression-free survival of patients with locally advanced, nonresectable adenocarcinoma of the pancreas treated with gemcitabine hydrochloride and oxaliplatin followed by concurrent radiotherapy, fluorouracil, and oxaliplatin. Secondary Determine the tolerability of this regimen, in both the short- and long-term, in these patients. Determine recurrence-free survival, overall survival, and response rate in patients treated with this regimen. Determine the quality of life of patients treated with this regimen. Determine the clinical benefits of this regimen in these patients. Determine locoregional and metastatic progression-free survival of patients treated with this regimen. OUTLINE: This is an open-label, multicenter study. Chemotherapy: Patients receive gemcitabine hydrochloride over 100 minutes on day 1 and oxaliplatin IV over 2 hours on day 2. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients are restaged at day 15-21 of the fourth course of chemotherapy. Patients with nonmetastatic disease proceed to chemoradiotherapy. Chemoradiotherapy: Patients undergo radiotherapy 5 days a week for 5 weeks. Patients also receive fluorouracil IV continuously in weeks 1-5 and oxaliplatin IV over 1 hour on days 1, 8, 15, 22, and 29 in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, at restaging, and at day 28 after completion of chemoradiotherapy. After completion of study treatment, patients are followed periodically for 5 years. PROJECTED ACCRUAL: A total of 58 patients will be accrued for this study.

adenocarcinoma of the pancreas, stage II pancreatic cancer, stage III pancreatic cancer, recurrent pancreatic cancer

DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the pancreas Locally advanced, nonresectable disease Residual disease after surgical resection (R1, R2) OR recurrent disease after radical surgery No visceral or peritoneal metastases No adenocarcinoma of the bile ducts or the ampulla of Vater PATIENT CHARACTERISTICS: ECOG performance status 0-2 Stable or controlled pain with analgesics Not pregnant or nursing Neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Creatinine ≤ 1.5 times normal OR < 3 mg/dL Creatinine clearance ≥ 40 mL/min Bilirubin ≤ 1.5 times normal Alkaline phosphatase < 5 times normal No medical condition that would preclude study treatment No active infection Negative pregnancy test No serious cardiac or respiratory disease No uncontrolled or persistent hypercalcemia No pre-existing neuropathy No biliary or gastro-duodenal obstruction No other malignancy except nonmelanomatous skin cancer, prostate cancer, or carcinoma in situ of the cervix or bladder No familial, social, geographical, or psychological condition that would preclude study compliance PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior abdominal radiotherapy (encompassing the liver, pancreas, or spleen) At least 2 months since prior radiotherapy

Moureau-Zabotto L, Phelip JM, Afchain P, Mineur L, Andre T, Vendrely V, Lledo G, Dupuis O, Huguet F, Touboul E, Balosso J, Louvet C. Concomitant administration of weekly oxaliplatin, fluorouracil continuous infusion, and radiotherapy after 2 months of gemcitabine and oxaliplatin induction in patients with locally advanced pancreatic cancer: a Groupe Coordinateur Multidisciplinaire en Oncologie phase II study. J Clin Oncol. 2008 Mar 1;26(7):1080-5. doi: 10.1200/JCO.2007.12.8223.

Moureau-Zabotto L, Phélip J, Afchain P, et al.: Concomitant administration of weekly oxaliplatin, 5FU continuous infusion and radiotherapy in locally advanced pancreatic cancer (LAPC): a Gercor phase II study. [Abstract] Int J Radiat Oncol Biol Phys 66 (3 Suppl 1): A-1077, S173-4, 2006.