induction chemotherapy, folfirinox followed with concurrent capecitabine and radiation therapy in inoperable locally advanced cancer of the pancreas

Conditions: Cancer of Pancreas

Summary: this prospective cohort, phase ii, trial is studying induction chemotherapy combination, folfirinox regimen, consisted of oxaliplatin, irinotecan, leucovorin and fluorouracil (5-fu), for 4 cycles, followed by consolidation concurrent radiotherapy with capecitabine in non-progressed cases, in treating patients with locally advanced cancer pancreas.

design \& methodology: 1. nature of the study: it is ( prospective cohort study). 2. study subjects: \*target population: patients, fulfilling the inclusion criteria for the research, will be selected from assiut clinical oncology department in assiut university hospitals. * sample size: 20 patients. * characteristics of subjects: * inclusion criteria: disease characteristics: * histological and radiological confirmation of locally advanced cancer pancreas * inoperable disease * disease must be able to be encompassed within a radical radiotherapy treatment volume * not metastatic patient characteristics: * ecog performance status 0 or 1 * life expectancy \> 3 months. * glomerular filtration rate ≥ 60 ml/min. * wbc \> 3,000/mm³. * absolute neutrophil count \> 1,500/mm³. * hemoglobin \> 10.0 g/dl. * platelet count \> 100,000/mm³. * alkaline phosphatase ≤ 1.5 times upper limit of normal (uln) * gamma-glutamyl-transferase \< 1.5 times uln. * transaminases ≤ 1.5 times uln. * bilirubin ≤ 1.5 times uln. * no medically unstable conditions (e.g., unstable diabetes, uncontrolled arterial hypertension, infection, hypercalcemia, or ischemic heart disease) * not pregnant or nursing. * no other previous or current malignant disease likely to interfere with protocol treatment or comparisons * no prior chemotherapy or radiotherapy. 3. patients \& methods: patients are randomized to one treatment arm. induction 4 times chemotherapy, folfirinox regimen, consisted of oxaliplatin at a dose of 85 mg/m2 on day 1 only, administered as a 2-hour intravenous infusion, with the addition, after 30 minutes, of irinotecan at a dose of 180 mg/m2 on day 1 only given as a 90-minute intravenous infusion. immediately will be followed by leucovorin at a dose of 200 mg/m2, given as a 2- hour intravenous infusion, day 1 and day 2 this treatment will be followed by fluorouracil (5-fu) dosed at 400 mg/m2, administered as an intravenous bolus on day 1 and day 2, followed by a continuous intravenous infusion of 600 /m2 over a 20- hours period on day 1 and day 2. treatment will be administered every 2 weeks. g-csf will be administrated according to the need. in non-progressed cases, induction chemotherapy will be followed by consolidation radiotherapy concurrent with capecitabine 625 mg/m2 bid. radiotherapy : a fractionated dose of 50.4gy /28 fraction/15 mev photon energy generated by dual-energetic linear accelerator. * gross target volume (gtv): visible tumor and lymph nodes. * clinical target volume (ctv): \[tumor/ affected lymph node + 1-2 cm\] + regional lymphatics lymphatics :corpus: upper and lower pancreaticoduodenal, superior and inferior pancreatic, celiac head: corpus lymphatics + porta hepatis lymphatics tail: corpus lymphatics (except pancreaticoduodenal ln) + splenic hilum ln * ptv: ctv + 1-1.5 cm * all patients will undergo a complete classical evaluation at the time of presentation which will be enrolled in a separate sheet for each patient. this will include a detailed history with estimation of the age of onset, the duration of the disease,. * detailed physical examination will be carried out treatment evaluation . laboratory examination include * complete blood count (cbc), * liver function test (lft) * renal function test (rft), * serum electrolytes at presentation and before each cycle of chemotherapy. radiographic examination include * abdominal multi detector computed tomography (mdct abdomen ) * chest x-ray before starting treatment, 2 weeks after ending phase 1 of treatment then 4 weeks after ending phase 2 of treatment then every 3 months for 18 months. ● bone scan will be done in those complaining from bone pain; elevated serum alkaline phosphatase or transaminase level * quality of life is assessed at baseline, monthly for 6 months, and then at each follow-up visit. after completion of study treatment, patients are followed periodically. response assessment : will be carried out, using (recist) response evaluation criteria in solid tumors, version 1.1 chemotherapy toxicity assessment: will be carried out, using (ctcae) common terminology criteria for adverse events, version 4.0 4. data analysis: data will be analysed using the computer program, statistical package for the social science (spss v.16). expected outcomes: the outcome of the study will be compared statistically with previous local and international trails. ethical considerations: 1. risk-benefit assessment: there is an acceptable risk may affect the patient in this research study as regard the acceptable side effects of gemcitabine, oxaliplatin and radiotherapy. 2. confidentiality: any data taken from the patient either from history, the examination or the investigations will be very confidential. 3. research statement: all patients subjected to this study will be informed about the procedures of the research. 4. informed consent: the study procedures will be discussed to all patients and consent will be taken from them. 5. other ethical concerns: the research will be conducted only by scientifically qualified and trained personnel.

Eligibility criteria:
inclusion criteria: * disease characteristics: * histological and radiological confirmation of locally advanced cancer pancreas * inoperable disease * disease must be able to be encompassed within a radical radiotherapy treatment volume * not metastatic patient characteristics: * ecog performance status 0 or 1 * life expectancy \> 3 months. * glomerular filtration rate ≥ 60 ml/min. * wbc \> 3,000/mm³. * absolute neutrophil count \> 1,500/mm³. * hemoglobin \> 10.0 g/dl. * platelet count \> 100,000/mm³. * alkaline phosphatase ≤ 1.5 times upper limit of normal (uln) * gamma-glutamyl-transferase \< 1.5 times uln. * transaminases ≤ 1.5 times uln. * bilirubin ≤ 1.5 times uln. * no medically unstable conditions (e.g., unstable diabetes, uncontrolled arterial hypertension, infection, hypercalcemia, or ischemic heart disease) * not pregnant or nursing. * no other previous or current malignant disease likely to interfere with protocol treatment or comparisons * no prior chemotherapy or radiotherapy. exclusion criteria: * ecog performance status \> 2 * life expectancy \< 3 months. * glomerular filtration rate \< 30 ml/min. * absolute neutrophil count \< 1,500/mm³. * alkaline phosphatase \> 1.5 times upper limit of normal (uln) * gamma-glutamyl-transferase \> 1.5 times uln. * transaminases\>1.5 times uln. * bilirubin \>1.5 times uln. * medically unstable conditions (e.g., unstable diabetes, uncontrolled arterial hypertension, infection, hypercalcemia, or ischemic heart disease) * pregnant or nursing. * prior chemotherapy or radiotherapy.

Keywords: locally advanced pancreatic cancer chemotherapy radiotherapy