pancreatic cancer is the fourth leading cause of cancer death in the western world and shows the worst mortality among common malignancies with a 5-year survival rate of lower than 5% .
the current standard of care includes surgical resection when appropriate and gemcitabine - based chemotherapy .
recent data suggests the use of folfirinox as initial treatment of patients with metastatic disease who have a good performance status improves survival .
single - agent gemcitabine is often administered to patients with advanced , metastatic pancreatic cancer .
studies with gemcitabine have demonstrated a significant clinical response ( decreased pain , increased functional status ) even in the absence of a measurable tumor response .
unfortunately , there is currently no standard second - line chemotherapy for metastatic pancreatic cancer .
one of the current major challenges is the lack of validated markers for prediction of response to chemotherapy in the metastatic pancreatic cancer setting .
a 49-year - old hispanic male , with a 25-pack year smoking history , moderate alcohol consumption and a family history reportedly noncontributory for gastrointestinal malignancies or liver disease , was found to have a biopsy - proven poorly differentiated ductal adenocarcinoma of the pancreas .
the patient had a past medical history of gastritis ; pancreatitis ; new onset insulin - dependent diabetes mellitus ; depression , and anxiety .
a diagnostic ct of the abdomen performed at an outside institution immediately prior to presentation to our center , revealed an infiltrative mass of the head of the pancreas measuring 4.6  3.5 cm in transverse and anteroposterior diameters and approximately 3.4 cm in longitudinal diameter , which was obstructing the common bile duct and pancreatic duct , infiltrating the peripancreatic and perivascular spaces and occluding the superior and mesenteric vein .
the pathology report described a poorly differentiated pancreatic adenocarcinoma that had metastasized to the liver .
the patient 's ca19 - 9 was 5,590 u / ml at presentation , and cea 2.8 u / ml ( both doubled in value over a period of approximately 2 weeks prior to presentation to our center ; table 1 ) .
symptoms at presentation consisted of fatigue and intermittent abdominal pain , controlled by pain medications ( opioids ) .
the patient also reported an approximately 79 kg weight loss over a period of 34 months ( weight at presentation 59.4 kg ) .
a ct - guided biopsy of the anterolateral right lobe liver lesion confirmed metastatic pancreas cancer .
the immunostains performed on paraffin sections were supportive of the above diagnosis : the tumor was positive for ck7 , ck20 and ca19 - 9 and negative for ttf1 .
it was decided to pursue with chemotherapy consisting of a doublet  gemcitabine and oxaliplatin ( gemox ) .
the patient received gemcitabine at 850 mg / m / dose on day 1 and day 8 and oxaliplatin at 100 mg / m / dose on day 2 , every 21 days .
the patient also received l - glutamine powder 15 g twice / day dissolved in protein shakes .
other supplements were taken along with chemotherapy ( self - administered ) : herbal mixtures anamu ( cuba ) and brim ( ecuador ) .
the first three cycles of chemotherapy were reasonably well tolerated without any significant side effects . the patient 's appetite and nutritional intake improved and weight gain was noted .
mild hyperkalemia was observed , presumed to be due to increased potassium intake ( nutritional shakes ) .
a pet / ct evaluation performed after 3 cycles of chemotherapy revealed decreased fdg uptake within the lesion in the head of the pancreas ( suv of 2.8 compared to 6.5 on previous examination ) and left adrenal gland ( suv 2.7 decreased from 3.8 ) , compatible with response to therapy .
there was complete resolution of the focus of mildly intense fdg uptake in the anterior right lobe of the liver .
new minimal fdg uptake was observed in the left lower lobe of the lung , presumed to be of inflammatory etiology . the ct scan of the abdomen showed overall decrease in size and volume of the pancreatic head lesion and of the tiny left adrenal nodule , as well as resolution of anterior right hepatic lesion consistent with response to therapy .
the patient completed 8 cycles of chemotherapy with complete radiographic and excellent tumor marker response ( ca19 - 9 level decreased from 5,590 u / ml to 130 u / ml ) and minimal symptoms . two treatment delays / dose reductions due to neutropenia developed during the 6-month treatment period . at the 1-month evaluation , the ca19 - 9 level continued to decrease from 130 u / ml to 55 u / ml , markedly decreased from 5,590 u / ml prior to initiation of therapy .
the ct scan of the chest , abdomen and pelvis , revealed no definite pancreatic masses or liver metastases .
the evaluation performed two months later , after a treatment break , showed essentially stable findings , with the ca19 - 9 slowly trending upwards to a value of 125 u / ml . at another 2-month interval , the pet / ct scan showed mild interval disease progression in the pancreatic head surrounding the common bile duct stent and interval progression of multifocal hepatic metastatic disease in both liver lobes , which was also evidenced on ct scan .
the radiographic changes were paralleled by the elevation of ca19 - 9 level from 125 to 7,730 u / ml . at this point in time
the patient was in overall good health , with good appetite and an ecog ps of 0 .
second - line therapy with gtx regimen was initiated consisting of the following dosages / schedule : gemcitabine 600 mg / m day 1 and day 8 , docetaxel 30 mg / m day 4 and day 11 , and capecitabine at 1,000 mg p.o .
an evaluation performed after 3 cycles of the second - line chemotherapy program revealed the patient to be doing reasonably well with mild numbness and tingling noted in the hands and feet .
he had lost approximately 1.8 kg in weight but otherwise remained in reasonably good health .
the ca19 - 9 level had decreased to 493 u / ml ( from 7,730 u / ml prior to the initiation of gtx regimen ) . the restaging ct scan of the chest , abdomen , and pelvis performed at this visit showed interval response to therapy of multifocal hepatic metastatic disease . at a subsequent evaluation performed after 5 cycles of this therapy there was continued evidence of a response , with the ct scan revealing a decreased size of the pancreatic head mass .
however , there was a mild increase in size of two previously noted liver lesions and one small lesion was unchanged in size from the previous examination .
the ca19 - 9 continued to decline and reached the level of 155 u / ml after 5 cycles of therapy , consistent with an ongoing treatment response .
treatment with gtx regimen continued and the patient completed 8 cycles with good overall tolerance . at this point imaging studies revealed stable disease with a slight increase in the ca19 - 9 level ( from 155 u / ml to 264 u / ml ) .
three months later the patient presented for a follow - up evaluation with reportedly increased epigastric and right upper quadrant pain , increased flatulence and a 4-kg weight loss during the previous two months .
. a restaging ct scan of the chest , abdomen and pelvis showed significant interval progression within the liver with a large heterogeneous 9-cm central mass centered at the hepatic hilum with near occlusion of the right portal vein and mild to moderate bilateral intrahepatic biliary ductal dilatation .
the ca19 - 9 level had increased from 264 to 90,200 u / ml . the treatment management plan consisted of initiation of third - line chemotherapy with gemcitabine and nab - paclitaxel ( abraxane ) .
the regimen dosages / schedule were as follows : gemcitabine 700 mg / m and nab - paclitaxel 70 mg / m , both administered on day 1 , 8 and 15 , every 28 days .
cycle 1 of nab - paclitaxel and gemcitabine was reasonably well tolerated with moderately well controlled pain in the epigastric area ( reportedly , the patient did not follow his pain regimen as indicated ) .
the patient was also seen by interventional radiology and was not considered to be a suitable candidate for chemoembolization at that point in time . in view of the excellent tolerance to the gemcitabine / nab - paclitaxel chemotherapy regimen ,
improvement in liver function tests and hematology parameters , a decision was made to increase the gemcitabine dose to 900 mg / m and the nab - paclitaxel dose to 100 mg / m . during this time the patient received hematological growth factor prophylaxis .
after 3 cycles of gemcitabine / nab - paclitaxel repeat imaging and tumor markers again demonstrated evidence of a favorable response .
the ca19 - 9 level was markedly decreased from 90,200 u / ml to 4,830 u / ml and the ct of chest / abdomen revealed less compression of the portal vein compared to the previous study .
the patient subsequently continued treatment with this regimen at an outside facility , eventually experiencing progression of the disease process . in summary , and of considerable interest , our patient lived for a total period of 2 years after his initial diagnosis of metastatic pancreatic carcinoma .
pancreatic cancer is one of the most lethal tumors of the gastrointestinal tract . the ability to predict which patients would benefit most from surgical intervention and/or chemotherapy would be a great clinical advance .
considerable research has focused on identifying molecular events in pancreatic carcinogenesis , and the correlation with clinicopathological variables of pancreatic tumors and survival . for the most part ,
the evidence regarding the application of biomarkers as prognostic indicators in this malignancy is conflicting .
the advent of gene microarray and mass spectrometric protein profiling offers the potential to examine many different biomarkers simultaneously .
this work may allow researchers to develop accurate and reproducible predictors of survival based on genetic signatures .
genetic and pharmacokinetic testing were not performed in our patient , but his exceptional response to chemotherapy treatments may lead to the conclusion that this patient 's pancreatic tumor may have had a unique genetic and molecular makeup .
highlights of this case report are a dramatic clinical , radiographic and serologic ( tumor markers ) response observed with each chemotherapy regimen administered , as well as significant improvement of the performance status and quality of life for our patient , secondary to chemotherapy treatment .
evidence supports the suggestion that treatment with gemcitabine / oxaliplatin is superior to gemcitabine alone in terms of response rate , clinical benefit rate and progression - free survival , but the differences did not reach the significant level for overall survival .
data for second - line therapy with gemcitabine - based regimens after first - line gemcitabine treatment have been published .
the combination of gemcitabine , docetaxel and capecitabine ( gtx ) is an active regimen in patients previously treated with gemcitabine for metastatic pancreatic cancer .
better performance status and > 75% drop in pretreatment ca19 - 9 were associated with longer survival .
gtx has a promising survival benefit of greater than 1 year in patients with advanced pancreatic adenocarcinoma when compared to studies using single agent gemcitabine or other combination chemotherapies .
following second line with gtx our patient experienced a significant response to a third - line gemcitabine - based regimen ( gemcitabine and nab - paclitaxel ) .
gemcitabine plus nab - paclitaxel has promising antitumor activity in unresectable and borderline resectable pancreatic cancer patients . pancreatic cancer cells and surrounding stroma are known to overexpress sparc ( secreted protein acid rich in cysteine ) , which is associated with poor clinical outcomes .
nab - paclitaxel , an albumin - bound nanoparticle form of paclitaxel , increased tumor accumulation of paclitaxel through binding of albumin to sparc .
a disease - specific phase 1 study was designed to evaluate the safety and efficacy of gemcitabine + nab - paclitaxel and the correlation of response with tumor sparc and serum ca19 - 9 levels .
the combination of nab - paclitaxel and gemcitabine was generally well tolerated and had substantial enough antitumor activity in patients with pancreatic cancer to warrant a phase iii clinical trial .
a number of possible hypotheses can be advanced for why our patient exhibited this unexpected degree of persistent sensitivity to gemcitabine - based chemotherapy , including an inability to repair chemotherapy - induced dna damage and a role for the glutamine supplementation he received during his treatment regimen .
hopefully , future research in this area will elucidate the reasons for such relatively favorable outcomes .
 pancreatic cancer exhibits profound chemoresistance resulting either from pre - existing ( intrinsic ) mechanisms , or from anticancer drug treatment itself ( acquired chemoresistance ) . we present the case of a patient with pancreatic adenocarcinoma metastatic to the liver who experienced clinical , radiographic and tumor marker response to three lines of gemcitabine - based chemotherapy . 
 the regimens included : 8 cycles of gemcitabine and oxaliplatin ( gemox ) , 8 cycles of gemcitabine , docetaxel and capecitabine ( gtx ) and more than 3 cycles of gemcitabine and nab - paclitaxel , with an exceptional response 2 years from the initiation of chemotherapy for metastatic pancreatic cancer . 
Introduction
Case Report
Discussion