Gemcitabine, Capecitabine, and Radiation Therapy in Treating Patients With Locally Advanced Pancreatic Cancer That Cannot Be Removed by Surgery

RATIONALE: Drugs used in chemotherapy, such as gemcitabine and capecitabine, 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 radiation therapy that uses a 3-dimensional image of the tumor to help focus thin beams of radiation directly on the tumor, and giving radiation therapy in higher doses over a shorter period of time, may kill more tumor cells and have fewer side effects. It is not yet known which regimen of chemotherapy given together with radiation therapy is more effective in treating pancreatic cancer. PURPOSE: This randomized phase II trial is comparing the side effects of two regimens of gemcitabine and capecitabine given together with radiation therapy and to see how well they work in treating patients with locally advanced pancreatic cancer that cannot be removed by surgery.

Sex

All

Minimum age

18 Years

Maximum age

120 Years

DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed adenocarcinoma of the pancreas

  * Locally advanced, nonmetastatic, inoperable, or operable (but medically unfit for surgery) disease

    * Palliative bypass procedure allowed
    * Common bile duct stenting allowed
* Primary pancreatic lesion ≤ 7 cm in diameter as measured by CT scan of the thorax and abdomen within 4 weeks prior to registration
* No recurrent cancer following definitive pancreatic surgery

PATIENT CHARACTERISTICS:

* WHO performance status (PS) 0-2
* Neutrophil count ≥ 1.5 x 10\^9/L
* Platelet count ≥ 100 x 10\^9/L
* Hemoglobin ≥ 10 g/dL
* Serum bilirubin \< 35 μmol/L (50 μmol/L allowed for patients who have had a recent biliary drain and whose bilirubin is descending)
* AST/ALT ≤ 2.5 times upper limit of normal (ULN)
* Alkaline phosphatase ≤ 5 times ULN
* GFR \> 50 mL/min
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 12 weeks after completion of study therapy
* No evidence of severe uncontrolled systemic diseases including uncontrolled coronary artery disease
* No myocardial infarction or stroke within the past 6 months
* No prior malignancies within the past 5 years except for carcinoma in situ of the cervix, adequately treated basal cell skin carcinoma, or any early-stage malignancy
* No suspected DPD deficiency
* No renal abnormalities (e.g., adult polycystic kidney disease, hydronephrosis, or ipsilateral single kidney)
* Must meet the following additional criteria for randomization:

  * WHO PS 0-1
  * Loss of weight no greater than 10% of that at baseline

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* At least 4 weeks since prior and no concurrent sorivudine or analogues
* No prior radiotherapy to the upper abdomen
* No concurrent methotrexate
* No concurrent allopurinol

• RESULTMukherjee S, Hurt CN, Bridgewater J, Falk S, Cummins S, Wasan H, Crosby T, Jephcott C, Roy R, Radhakrishna G, McDonald A, Ray R, Joseph G, Staffurth J, Abrams RA, Griffiths G, Maughan T. Gemcitabine-based or capecitabine-based chemoradiotherapy for locally advanced pancreatic cancer (SCALOP): a multicentre, randomised, phase 2 trial. Lancet Oncol. 2013 Apr;14(4):317-26. doi: 10.1016/S1470-2045(13)70021-4. Epub 2013 Mar 6. PMID 23474363
• RESULTFokas E, Spezi E, Patel N, Hurt C, Nixon L, Chu KY, Staffurth J, Abrams R, Mukherjee S. Comparison of investigator-delineated gross tumour volumes and quality assurance in pancreatic cancer: Analysis of the on-trial cases for the SCALOP trial. Radiother Oncol. 2016 Aug;120(2):212-6. doi: 10.1016/j.radonc.2016.07.002. Epub 2016 Aug 3. PMID 27497804
• RESULTFokas E, Clifford C, Spezi E, Joseph G, Branagan J, Hurt C, Nixon L, Abrams R, Staffurth J, Mukherjee S. Comparison of investigator-delineated gross tumor volumes and quality assurance in pancreatic cancer: Analysis of the pretrial benchmark case for the SCALOP trial. Radiother Oncol. 2015 Dec;117(3):432-7. doi: 10.1016/j.radonc.2015.08.026. Epub 2015 Aug 29. PMID 26328939