title: Single-fraction stereotactic body radiation therapy and sequential gemcitabine for the treatment of locally advanced pancreatic cancer. Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group. Neurolytic sympathectomy in the management of cancer pain-time effect: a prospective, randomized multicenter study. Health-Related Quality of Life in SCALOP, a Randomized Phase 2 Trial Comparing Chemoradiation Therapy Regimens in Locally Advanced Pancreatic Cancer Gemcitabine-based or capecitabine-based chemoradiotherapy for locally advanced pancreatic cancer (SCALOP): a multicentre, randomised, phase 2 trial Phase II trial of cetuximab, gemcitabine, and oxaliplatin followed by chemoradiation with cetuximab for locally advanced (T4) pancreatic adenocarcinoma: correlation of Smad4(Dpc4) immunostaining with pattern of disease progression. Phase I study of stereotactic radiosurgery in patients with locally advanced pancreatic cancer. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. Gemcitabine chemotherapy and single-fraction stereotactic body radiotherapy for locally advanced pancreatic cancer. Effect of neurolytic celiac plexus block on pain relief, quality of life, and survival in patients with unresectable pancreatic cancer: a randomized controlled trial. Tissue Factor Expression, Angiogenesis, and Thrombosis in Pancreatic Cancer Phase 2 Multi-institutional Trial Evaluating Gemcitabine and Stereotactic Body Radiotherapy for Patients With Locally Advanced Unresectable Pancreatic Adenocarcinoma Evaluating the Impact of a Single-Day Multidisciplinary Clinic on the Management of Pancreatic Cancer Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial--SAKK 44/00-CECOG/PAN.1.3.001. Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303). Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group Trial E2297. Gemcitabine versus gemcitabine plus dalteparin thromboprophylaxis in pancreatic cancer. Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. Randomized phase III multi-institutional study of TNFerade biologic with fluorouracil and radiotherapy for locally advanced pancreatic cancer: final results. Phase III Trial of Radiosensitizer PR-350 Combined With Intraoperative Radiotherapy for the Treatment of Locally Advanced Pancreatic Cancer Erlotinib 150 mg daily plus chemotherapy in advanced pancreatic cancer: an interim safety analysis of a multicenter, randomized, cross-over phase III trial of the ‘Arbeitsgemeinschaft Internistische Onkologie’ Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. Using economic analysis to evaluate the potential of multimodality therapy for elderly patients with locally advanced pancreatic cancer. BAYPAN study: a double-blind phase III randomized trial comparing gemcitabine plus sorafenib and gemcitabine plus placebo in patients with advanced pancreatic cancer. The Role of Stereotactic Body Radiation Therapy for Pancreatic Cancer: A Single-Institution Experience Multicenter randomized phase III trial comparing protracted venous infusion (PVI) fluorouracil (5-FU) with PVI 5-FU plus mitomycin in inoperable pancreatic cancer. Concurrent chemoradiotherapy treatment of locally advanced pancreatic cancer: gemcitabine versus 5-fluorouracil, a randomized controlled study. Geriatric Assessment Improves Prediction of Surgical Outcomes in Older Adults Undergoing Pancreaticoduodenectomy: A Prospective Cohort Study Placebo controlled trial of enteric coated pancreatin microsphere treatment in patients with unresectable cancer of the pancreatic head region Phase-II study on stereotactic radiotherapy of locally advanced pancreatic carcinoma. A randomized phase III study of radiotherapy alone or with 5-fluorouracil and mitomycin-C in patients with locally advanced adenocarcinoma of the pancreas: Eastern Cooperative Oncology Group study E8282. Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study. Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer. Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000-01 FFCD/SFRO study. Gemcitabine plus erlotinib followed by capecitabine versus capecitabine plus erlotinib followed by gemcitabine in advanced pancreatic cancer: final results of a randomised phase 3 trial of the ‘Arbeitsgemeinschaft Internistische Onkologie’ (AIO-PK0104)
abstract: PURPOSE This Phase II trial evaluated the toxicity , local control , and overall survival in patients treated with sequential gemcitabine and linear accelerator-based single-fraction stereotactic body radiotherapy ( SBRT ) .  METHODS AND MATERIAL S Twenty patients with locally advanced , nonmetastatic pancreatic adenocarcinoma were enrolled on this prospect i ve single-institution , institutional review board-approved study . Gemcitabine was administered on Days 1 , 8 , and 15 , and SBRT on Day 29 . Gemcitabine was restarted on Day 43 and continued for 3 - 5 cycles . SBRT of 25 Gy in a single fraction was delivered to the internal target volume with a 2- 3-mm margin using a nine-field intensity-modulated radiotherapy technique . Respiratory gating was used to account for breathing motion . Follow-up evaluations occurred at 4 - 6 weeks , 10 - 12 weeks , and every 3 months after SBRT . RESULTS All patients completed SBRT and a median of five cycles of chemotherapy . Follow-up for the 2 remaining alive patients was 25.1 and 36.4 months . No acute Grade 3 or greater nonhematologic toxicity was observed . Late Grade 3 or greater toxicities occurred in 1 patient ( 5 % ) and consisted of a duodenal perforation ( G4 ) . Three patients ( 15 % ) developed ulcers ( G2 ) that were medically managed . Overall , median survival was 11.8 months , with 1-year survival of 50 % and 2-year survival of 20 % . Using serial computed tomography , the freedom from local progression was 94 % at 1 year . CONCLUSION Linear accelerator-delivered SBRT with sequential gemcitabine result ed in excellent local control of locally advanced pancreatic cancer . Future studies will address strategies for reducing long-term duodenal toxicity associated with SBRT PURPOSE This phase III trial compared the efficacy and safety of gemcitabine ( Gem ) plus capecitabine ( GemCap ) versus single-agent Gem in advanced/metastatic pancreatic cancer . PATIENTS AND METHODS Patients were r and omly assigned to receive GemCap ( oral capecitabine 650 mg/m2 twice daily on days 1 to 14 plus Gem 1,000 mg/m2 by 30-minute infusion on days 1 and 8 every 3 weeks ) or Gem ( 1,000 mg/m2 by 30-minute infusion weekly for 7 weeks , followed by a 1-week break , and then weekly for 3 weeks every 4 weeks ) . Patients were stratified according to center , Karnofsky performance score ( KPS ) , presence of pain , and disease extent . RESULTS A total of 319 patients were enrolled between June 2001 and June 2004 .  Median overall survival ( OS ) time , the primary end point , was 8.4 and 7.2 months in the GemCap and Gem arms , respectively ( P = .234 ) . Post hoc analysis in patients with good KPS ( score of 90 to 100 ) showed a significant prolongation of median OS time in the GemCap arm compared with the Gem arm ( 10.1 v 7.4 months , respectively ; P = .014 ) . The overall frequency of grade 3 or 4 adverse events was similar in each arm . Neutropenia was the most frequent grade 3 or 4 adverse event in both arms . CONCLUSION GemCap failed to improve OS at a statistically significant level compared with st and ard Gem treatment . The safety of GemCap and Gem was similar . In the subgroup of patients with good performance status , median OS was improved significantly . GemCap is a practical regimen that may be considered as an alternative to single-agent Gem for the treatment of advanced/metastatic pancreatic cancer patients with a good performance status CONTEXT Sympathectomy is currently used as the fourth step of the modified World Health Organization ( WHO ) analgesic ladder . Sympathectomy can be performed early , before the second step on the ladder . OBJECTIVES We hypothesized that early sympathectomy would reduce pain and opioid consumption and improve quality of life . METHODS One hundred nine patients , with inoperable abdominal or pelvic cancer , reporting visceral pain of 40 - 70 on a visual analogue scale and taking nonopioid analgesics  were allocated r and omly into two groups : either blocks were performed before Step 2 of the WHO ladder , then analgesics were managed according to the ladder ( Group I ) or analgesics were given according to the WHO ladder , and blocks were performed as the fourth step after failure of strong opioids to control pain ( Group II ) . Visual analogue scale scores , responder analysis , daily opioid consumption , related side effects , and quality of life were assessed . RESULTS Responders were significantly higher in Group I ( P < 0.0001 ) , and partial responders and nonresponders significantly increased in Group II ( P < 0.0001 and 0.006 , respectively ) . Opioid consumption significantly decreased in Group I ( P < 0.0001 during first 12 months and 0.007 at the last assessment time ) , with concomitant significant reduction in related side effects . The number of patients who had a good analgesic response on tramadol significantly increased in Group I during the first five months ( P < 0.05 ) . European Organization for Research and Treatment of Cancer Quality of Life Question naire-Core 30 global quality -of-life subscale scores revealed significant improvement until the fifth month in Group I ( P < 0.05 ) . CONCLUSION Sympathectomy before Step 2 on the WHO analgesic ladder seems to lead to better pain control , less opioid consumption , and better quality of life in cancer patients Purpose Chemoradiation therapy ( CRT ) for patients with locally advanced pancreatic cancer ( LAPC ) provides survival benefits but may result in considerable toxicity . Health-related quality of life ( HRQL ) measurements during CRT have not been widely reported . This paper reports HRQL data from the Selective Chemoradiation in Advanced Localised Pancreatic Cancer ( SCALOP ) trial , including validation of the QLQ-PAN26 tool in CRT . Methods and Material s Patients with locally advanced , inoperable , nonmetastatic carcinoma of the pancreas were eligible . Following 12 weeks of induction gemcitabine plus capecitabine ( GEMCAP ) chemotherapy , patients with stable and responding disease were r and omized to a further cycle of GEMCAP followed by capecitabine- or gemcitabine-based CRT .  HRQL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Question naire ( EORTC QLQ-C30 ) and the EORTC Pancreatic Cancer module ( PAN26 ) . Results A total of 114 patients from 28 UK centers were registered and 74 patients r and omized . There was improvement in the majority of HRQL scales during induction chemotherapy . Patients with significant deterioration in fatigue , appetite loss , and gastrointestinal symptoms during CRT recovered within 3 weeks following CRT . Differences in changes in HRQL scores between trial arms rarely reached statistical significance ; however , where they did , they favored capecitabine therapy . PAN26 scales had good internal consistency and were able to distinguish between subgroups of patients experiencing toxicity . Conclusions Although there is deterioration in HRQL following CRT , this resolves within 3 weeks . HRQL data support the use of capecitabine- over gemcitabine-based chemoradiation . The QLQ-PAN26 is a reliable and valid tool for use in patients receiving CRT Summary Background In the UK , chemotherapy is the st and ard treatment for inoperable , locally advanced , non-metastatic pancreatic cancer .  Chemoradiotherapy is also an acceptable treatment option , for which gemcitabine , fluorouracil , or capecitabine can be used as concurrent chemotherapy agents . We aim ed to assess the activity , safety , and feasibility of both gemcitabine-based and capecitabine-based chemoradiotherapy after induction chemotherapy for patients with locally advanced pancreatic cancer . Methods In this open-label , r and omised , two-arm , phase 2 trial , patients aged 18 years or older with histologically proven , locally advanced pancreatic cancer ( with a tumour diameter of 7 cm or less ) were recruited from 28 UK centres between Dec 24 , 2009 and Oct 25 , 2011 . After 12 weeks of induction gemcitabine and capecitabine chemotherapy ( three cycles of gemcitabine [ 1000 mg/m2 on days 1 , 8 , 15 of a 28-day cycle ] and capecitabine [ 830 mg/m2 twice daily on days 1–21 of a 28-day cycle ] ) , patients with stable or responding disease , tumour diameter of 6 cm or less , and WHO performance status 0–1 were r and omly assigned to receive a further cycle of gemcitabine and capecitabine chemotherapy followed by either gemcitabine ( 300 mg/m2 once per week ) or capecitabine ( 830 mg/m2 twice daily , Monday to Friday only ) , both in combination with radiation ( 50·4 Gy in 28 fractions ) . R and omisation ( 1:1 ) was done via a central computerised system and used stratified minimisation . The primary endpoint was 9-month progression-free survival , analysed by intention to treat including only those patients with valid CT assessment s. This trial is registered with IS RCT N , number 96169987 . Findings 114 patients were registered and 74 were r and omly allocated ( 38 to the gemcitabine group and 36 to the capecitabine group ) . After 9 months , 22 of 35 assessable patients ( 62·9 % , 80 % CI 50·6–73·9 ) in the capecitabine group and 18 of 35 assessable patients ( 51·4 % , 39·4–63·4 ) in the gemcitabine group had not progressed . Median overall survival was 15·2 months ( 95 % CI 13·9–19·2 ) in the capecitabine group and 13·4 months ( 95 % CI 11·0–15·7 ) in the gemcitabine group ( adjusted hazard ratio [ HR ] 0·39 , 95 % CI 0·18–0·81 ; p=0·012 ) . 12-month overall survival was 79·2 % ( 95 % CI 61·1–89·5 ) in the capecitabine group and 64·2 ( 95 % CI 46·4–77·5 ) in the gemcitabine group . Median progression-free survival was 12·0 months ( 95 % CI 10·2–14·6 ) in the capecitabine group and 10·4 months ( 95 % CI 8·9–12·5 ) in the gemcitabine group ( adjusted HR 0·60 , 95 % CI 0·32–1·12 ; p=0·11 ) . Eight patients in the capecitabine group had an objective response at 26 weeks , as did seven in the gemcitabine group . More patients in the gemcitabine group than in the capecitabine group had grade 3–4 haematological toxic effects ( seven [ 18 % ] vs none , p=0·008 ) and non-haematological toxic effects ( ten [ 26 % ] vs four [ 12 % ] , p=0·12 ) during chemoradiation treatment ; the most frequent events were leucopenia , neutropenia , and fatigue . Two patients in the capecitabine group progressed during the fourth cycle of induction chemotherapy . Of the 34 patients in the capecitabine group who received chemoradiotherapy , 25 ( 74 % ) received the full protocol dose of radiotherapy , compared with 26 ( 68 % ) of 38 patients in the gemcitabine group . Quality -of-life scores were not significantly different between the treatment groups . Interpretation Our results suggest that a capecitabine-based regimen might be preferable to a gemcitabine-based regimen in the context of consolidation chemoradiotherapy after a course of induction chemotherapy for locally advanced pancreatic cancer . However , these findings should be interpreted with caution because the difference in the primary endpoint was non-significant and the number of patients in the trial was small . Funding Cancer Research UK PURPOSE This phase II trial was design ed to assess the efficacy and safety of cetuximab , gemcitabine , and oxaliplatin followed by cetuximab , capecitabine , and radiation therapy in locally advanced pancreatic cancer ( LAPC ) . PATIENTS AND METHODS Treatment-naive eligible patients ( n = 69 ) received intravenous gemcitabine ( 1,000 mg/m(2 ) ) and oxaliplatin ( 100 mg/m(2 ) ) every 2 weeks for four doses , followed by radiation ( 50.4 Gy to the gross tumor only ) with concurrent capecitabine ( 825 mg/m(2 ) twice daily on radiation treatment days ) . Cetuximab ( 500 mg/m(2 ) ) was started on day 1 of chemotherapy and was continued every 2 weeks during chemotherapy and chemoradiotherapy . Diagnostic cytology specimens were immunostained for Smad4(Dpc4 ) expression . RESULTS Median overall survival time was 19.2 months ( 95 % CI , 14.2 to 24.2 months ) , and 1-year , 2-year , and 4-year actuarial overall survival rates were 66.0 % , 25.02 % , and 11.3 % , respectively . Acneiform rash correlated with improved survival ( P = .001 ) , but initial CA19 - 9 , borderline resectable initial stage , and surgical resection ( n = 7 ) did not . The 1-year and 2-year radiographic local progression rates were 22.8 % and 61.0 % , respectively . The worst acute toxic effects were GI toxicity ( 32 % and 10 % for grade s 2 and 3 , respectively ) ; fatigue ( 26 % and 6 % for grade s 2 and 3 , respectively ) ; sensory neuropathy ( 9 % and 1 % for grade s 2 and 3 , respectively ) ; and acneiform rash ( 54 % and 3 % for grade s 2 and 3 , respectively ) . Smad4(Dpc4 ) expression correlated with a local rather than a distant dominant pattern of disease progression ( P = .016 ) . CONCLUSION This regimen appears effective and has acceptable toxicity . The primary end point ( 1-year overall survival rate > 45 % ) was met , with encouraging survival duration . Smad4(Dpc4 ) immunostaining correlated with the pattern of disease progression . Prospect i ve validation of Smad4(Dpc4 ) expression in cytology specimens as a predictive biomarker is warranted and may lead to personalized treatment strategies for patients with localized pancreatic cancer PURPOSE To determine the feasibility and toxicity of delivering stereotactic radiosurgery to patients with locally advanced pancreatic cancer . METHODS AND MATERIAL S Patients with Eastern Cooperative Oncology Group performance status < or=2 and locally advanced pancreatic cancer were enrolled on this Phase I dose escalation study . Patients received a single fraction of radiosurgery consisting of either 15 Gy , 20 Gy , or 25 Gy to the primary tumor . Acute gastrointestinal toxicity was scored according to the Radiation Therapy Oncology Group criteria . Response to treatment was determined by serial high-resolution computed tomography scanning . RESULTS Fifteen patients were treated at 3 dose levels ( 3 patients received 15 Gy , 5 patients received 20 Gy , and 7 patients received 25 Gy ) . At these doses , no Grade 3 or higher acute gastrointestinal toxicity was observed . This trial was stopped before any dose-limiting toxicity was reached , because the clinical objective of local control was achieved in all 6 evaluable patients treated at 25 Gy . CONCLUSIONS It is feasible to deliver stereotactic radiosurgery to patients with locally advanced pancreatic cancer . The recommended dose to achieve local control without significant acute gastrointestinal toxicity is 25 Gy BACKGROUND In a phase 1 - 2 trial of albumin-bound paclitaxel ( nab-paclitaxel ) plus gemcitabine , substantial clinical activity was noted in patients with advanced pancreatic cancer . We conducted a phase 3 study of the efficacy and safety of the combination versus gemcitabine monotherapy in patients with metastatic pancreatic cancer . METHODS We r and omly assigned patients with a Karnofsky performance-status score of 70 or more ( on a scale from 0 to 100 , with higher scores indicating better performance status ) to nab-paclitaxel ( 125 mg per square meter of body-surface area ) followed by gemcitabine  ( 1000 mg per square meter ) on days 1 , 8 , and 15 every 4 weeks or gemcitabine monotherapy ( 1000 mg per square meter ) weekly for 7 of 8 weeks ( cycle 1 ) and then on days 1 , 8 , and 15 every 4 weeks ( cycle 2 and subsequent cycles ) . Patients received the study treatment until disease progression . The primary end point was overall survival ; secondary end points were progression-free survival and overall response rate . RESULTS A total of 861 patients were r and omly assigned to nab-paclitaxel plus gemcitabine ( 431 patients ) or gemcitabine  ( 430 ) . The median overall survival was 8.5 months in the nab-paclitaxel-gemcitabine group as compared with 6.7 months in the gemcitabine group ( hazard ratio for death , 0.72 ; 95 % confidence interval [ CI ] , 0.62 to 0.83 ; P<0.001 ) . The survival rate was 35 % in the nab-paclitaxel-gemcitabine group versus 22 % in the gemcitabine group at 1 year , and 9 % versus 4 % at 2 years . The median progression-free survival was 5.5 months in the nab-paclitaxel-gemcitabine group , as compared with 3.7 months in the gemcitabine group ( hazard ratio for disease progression or death , 0.69 ; 95 % CI , 0.58 to 0.82 ; P<0.001 ) ; the response rate according to independent review was 23 % versus 7 % in the two groups ( P<0.001 ) . The most common adverse events of grade 3 or higher were neutropenia ( 38 % in the nab-paclitaxel-gemcitabine group vs. 27 % in the gemcitabine group ) , fatigue ( 17 % vs. 7 % ) , and neuropathy ( 17 % vs. 1 % ) . Febrile neutropenia occurred in 3 % versus 1 % of the patients in the two groups . In the nab-paclitaxel-gemcitabine group , neuropathy of grade 3 or higher improved to grade 1 or lower in a median of 29 days . CONCLUSIONS In patients with metastatic pancreatic adenocarcinoma , nab-paclitaxel plus gemcitabine significantly improved overall survival , progression-free survival , and response rate , but rates of peripheral neuropathy and myelosuppression were increased . ( Funded by Celgene ; Clinical Trials.gov number , NCT00844649 . ) PURPOSE Fractionated radiotherapy and chemotherapy for locally advanced pancreatic cancer achieves only modest local control . This prospect i ve trial evaluated the efficacy of a single fraction of 25 Gy stereotactic body radiotherapy ( SBRT ) delivered between Cycle 1 and 2 of gemcitabine chemotherapy . METHODS AND MATERIAL S A total of 16 patients with locally advanced , nonmetastatic , pancreatic adenocarcinoma received  gemcitabine with SBRT delivered 2 weeks after completion of the first cycle . Gemcitabine was resumed 2 weeks after SBRT and was continued until progression or dose-limiting toxicity . The gross tumor volume , with a 2 - 3-mm margin , was treated in a single 25-Gy fraction by Cyberknife . Patients were evaluated at 4 - 6 weeks , 10 - 12 weeks , and every 3 months after SBRT . RESULTS All 16 patients completed SBRT . A median of four cycles ( range one to nine ) of chemotherapy was delivered . Three patients ( 19 % ) developed local disease progression at 14 , 16 , and 21 months after SBRT . The median survival was 11.4 months , with 50 % of patients alive at 1 year . Patients with normal  carbohydrate antigen (CA)19 - 9 levels either at diagnosis or after Cyberknife SBRT had longer survival ( p < 0.01 ) . Acute gastrointestinal toxicity was mild , with 2 cases of Grade 2 ( 13 % ) and 1 of Grade 3 ( 6 % ) toxicity . Late gastrointestinal toxicity was more common , with five ulcers ( Grade 2 ) , one duodenal stenosis ( Grade 3 ) , and one duodenal perforation ( Grade 4 ) . A trend toward increased duodenal volumes radiated was observed in those experiencing late effects ( p = 0.13 ) . CONCLUSION SBRT with gemcitabine result ed in comparable survival to conventional chemoradiotherapy and good local control . However , the rate of duodenal ulcer development was significant CONTEXT Pancreatic cancer is an aggressive tumor associated with high mortality . Optimal pain control may improve quality of life ( QOL ) for these patients . OBJECTIVE To test the hypothesis that neurolytic celiac plexus block ( NCPB ) vs opioids alone improves pain relief , QOL , and survival in patients with unresectable pancreatic cancer . DESIGN , SETTING , AND PATIENTS Double-blind , r and omized clinical trial conducted at Mayo Clinic , Rochester , Minn. Enrolled ( October 1997 and January 2001 ) were 100 eligible patients with unresectable pancreatic cancer experiencing pain . Patients were followed up for at least 1 year or until death . INTERVENTION Patients were r and omly assigned to receive either NCPB or systemic analgesic therapy alone with a sham injection . All patients could receive additional opioids managed by a clinician blinded to the treatment assignment . MAIN OUTCOME MEASURES Pain intensity ( 0 - 10 numerical rating scale ) , QOL , opioid consumption and related adverse effects , and survival time were assessed weekly by a blinded observer . RESULTS Mean ( SD ) baseline pain was 4.4 ( 1.7 ) for NCPB vs 4.1 ( 1.8 ) for opioids alone . The first week after r and omization , pain intensity and QOL scores were improved ( pain intensity , P < or = .01 for both groups ; QOL , P<.001 for both groups ) , with a larger decrease in pain for the NCPB group ( P = .005 ) . From repeated measures analysis , pain was also lower for NCPB over time ( P = .01 ) . However , opioid consumption ( P = .93 ) , frequency of opioid adverse effects ( all P>.10 ) , and QOL ( P = .46 ) were not significantly different between groups . In the first 6 weeks , fewer NCPB patients reported moderate or severe pain ( pain intensity rating of > or = 5/10 ) vs opioid-only patients ( 14 % vs 40 % , P = .005 ) . At 1 year , 16 % of NCPB patients and 6 % of opioid-only patients were alive . However , survival did not differ significantly between groups ( P = .26 , proportional hazards regression ) . CONCLUSION Although NCPB improves pain relief in patients with pancreatic cancer vs optimized systemic analgesic therapy alone , it does not affect QOL or survival Purpose : Hemostatic activation is common in pancreatic cancer and may be linked to angiogenesis and venous thromboembolism . We investigated expression of  tissue factor ( TF ) , the prime initiator of coagulation , in noninvasive and invasive pancreatic neoplasia . We correlated TF expression with vascular endothelial growth factor ( VEGF ) expression , microvessel density , and venous thromboembolism in resected pancreatic cancer . Experimental Design : Tissue cores from a tri-institutional retrospective series of patients were used to build tissue microarrays . TF expression was grade d semiquantitatively using immunohistochemistry in normal pancreas ( n = 10 ) , intraductal papillary mucinous neoplasms ( n = 70 ) , pancreatic intraepithelial neoplasia ( n = 40 ) , and resected or metastatic pancreatic adenocarcinomas ( n = 130 ) . Results : TF expression was observed in a majority of noninvasive and invasive pancreatic neoplasia , including 77 % of pancreatic intraepithelial neoplasias , 91 % of intraductal papillary mucinous neoplasms , and 89 % of pancreatic cancers , but not in normal pancreas . Sixty-six of 122 resected pancreatic cancers ( 54 % ) were found to have high TF expression ( defined as grade ≥2 , the median score ) . Carcinomas with high TF expression were more likely to also express VEGF ( 80 % versus 27 % with low TF expression , P < 0.0001 ) and had a higher median MVD ( 8 versus 5 per tissue core with low TF expression , P = 0.01 ) . Pancreatic cancer patients with high TF expression  had a venous thromboembolism rate of 26.3 % compared with 4.5 % in patients with low TF expression ( P = 0.04 ) . Conclusions : TF expression occurs early in pancreatic neoplastic transformation and is associated with VEGF expression , increased microvessel density , and possibly clinical venous thromboembolism in pancreatic cancer . Prospect i ve studies evaluating the role of TF in pancreatic cancer outcomes are warranted This phase 2 multi‐institutional study was design ed to determine whether gemcitabine ( GEM ) with fractionated stereotactic body radiotherapy ( SBRT ) results in acceptable late grade 2 to 4 gastrointestinal toxicity when compared with a prior trial of GEM with single‐fraction SBRT in patients with locally advanced pancreatic cancer ( LAPC ) Purpose To evaluate the impact of a multidisciplinary clinic on the clinical care recommendations of patients with pancreatic cancer compared with the recommendations the patients received prior to review by the multidisciplinary tumor board . Methods The records of 203 consecutive patients referred to the Johns Hopkins pancreatic multidisciplinary clinic were prospect ively collected from November 2006 to October 2007 .  Cross-sectional imaging , pathology , and medical history were evaluated by a panel of medical/radiation oncologists , surgical oncologists , pathologists , diagnostic radiologists , and geneticists . Alterations in treatment recommendations between the outside institution and the multidisciplinary clinic were recorded and compared . Results On presentation , the outside computed tomography ( CT ) report described locally advanced/unresectable disease ( 34.9 % ) , metastatic disease ( 17.7 % ) , and locally advanced disease with metastasis ( 1.1 % ) . On review of su bmi tted imaging and imaging performed at Hopkins , 38 out of 203 ( 18.7 % ) patients had a change in the status of their clinical stage . Review of the histological slides by dedicated pancreatic pathologists result ed in changes in the interpretation for 7 of 203 patients ( 3.4 % ) . Overall , 48 out of 203 ( 23.6 % ) patients had a change in their recommended management based on clinical review of their case by the multidisciplinary tumor board . Enrollment into the National Familial Pancreas Tumor Registry increased from 52 out of 106 ( 49.2 % ) patients in 2005 to 158 out of 203 ( 77.8 % ) with initiation of the multidisciplinary clinic . Conclusion The single-day pancreatic multidisciplinary clinic provided a comprehensive and coordinated evaluation of patients that led to changes in therapeutic recommendations in close to one-quarter of patients PURPOSE To compare clinical benefit response ( CBR ) and quality of life ( QOL ) in patients receiving gemcitabine ( Gem ) plus capecitabine ( Cap ) versus  single-agent Gem for advanced/metastatic pancreatic cancer . PATIENTS AND METHODS Patients were r and omly assigned to receive GemCap ( oral Cap 650 mg/m(2 ) twice daily on days 1 through 14 plus Gem 1,000 mg/m(2 ) in a 30-minute infusion on days 1 and 8 every 3 weeks ) or Gem ( 1,000 mg/m(2 ) in a 30-minute infusion weekly for 7 weeks , followed by a 1-week break , and then weekly for 3 weeks every 4 weeks ) for 24 weeks or until progression . CBR criteria and QOL indicators were assessed over this period . CBR was defined as improvement from baseline for > or= 4 consecutive weeks in pain ( pain intensity or analgesic consumption ) and Karnofsky performance status , stability in one but improvement in the other , or stability in pain and performance status but improvement in weight . RESULTS Of 319 patients , 19 % treated with GemCap and 20 % treated with Gem experienced a CBR , with a median duration of 9.5 and 6.5 weeks , respectively ( P < .02 ) ; 54 % of patients treated with GemCap and 60 % treated with Gem had no CBR ( remaining patients were not assessable ) . There was no treatment difference in QOL ( n = 311 ) . QOL indicators were improving under chemotherapy ( P < .05 ) . These changes differed by the time to failure , with a worsening 1 to 2 months before treatment failure ( all P < .05 ) . CONCLUSION There is no indication of a difference in CBR or QOL between GemCap and Gem . Regardless of their initial condition , some patients experience an improvement in QOL on chemotherapy , followed by a worsening before treatment failure PURPOSE The purpose of this trial was to evaluate the role of radiation therapy with concurrent gemcitabine ( GEM ) compared with GEM alone in patients with localized unresectable pancreatic cancer . PATIENTS AND METHODS Patients with localized unresectable adenocarcinoma of the pancreas were r and omly assigned to receive GEM alone ( at 1,000 mg/m(2)/wk for weeks 1 to 6 , followed by 1 week rest , then for 3 of 4 weeks ) or GEM ( 600 mg/m(2)/wk for weeks 1 to 5 , then 4 weeks later 1,000 mg/m(2 ) for 3 of 4 weeks ) plus radiotherapy ( starting on day 1 , 1.8 Gy/Fx for total of 50.4 Gy ) . Measurement of quality of life using the Functional Assessment of Cancer Therapy-Hepatobiliary question naire was also performed . RESULTS Of 74 patients entered on trial and r and omly assigned to receive GEM alone ( arm A ; n = 37 ) or GEM plus radiation ( arm B ; n = 34 ) , patients in arm B had greater incidence of grade s 4 and 5 toxicities ( 41 % v 9 % ) , but grade s 3 and 4 toxicities combined were similar ( 77 % in A v 79 % in B ) . No statistical differences were seen in quality of life measurements at 6 , 15 to 16 , and 36 weeks . The primary end point was survival , which was 9.2 months ( 95 % CI , 7.9 to 11.4 months ) and 11.1 months ( 95 % CI , 7.6 to 15.5 months ) for arms A and B , respectively ( one-sided P = .017 by stratified log-rank test ) . CONCLUSION This trial demonstrates improved overall survival with the addition of radiation therapy to GEM in patients with localized unresectable pancreatic cancer , with acceptable toxicity PURPOSE The combination of gemcitabine plus bevacizumab produced a 21 % response rate and a median survival of 8.8 months in a multicenter phase II trial in patients with metastatic pancreatic cancer . These encouraging data led Cancer and Leukemia Group B ( CALGB ) to conduct a double-blind , placebo-controlled , r and omized phase III trial of gemcitabine/bevacizumab versus gemcitabine/placebo in advanced pancreatic cancer patients . PATIENTS AND METHODS Eligible patients had no prior therapy for advanced disease , Eastern Cooperative Oncology Group ( ECOG ) performance status 0 to 2 , no tumor invasion of adjacent organs , and no increased bleeding risk . The primary end point was overall survival . Patients were stratified by performance status , extent of disease , and prior radiotherapy . Patients received gemcitabine at 1,000 mg/m(2 ) over 30 minutes on days 1 , 8 , and 15 every 28 days and bevacizumab at 10 mg/kg or placebo on days 1 and 15 every 28 days . RESULTS Between June 2004 and April 2006 , 602 patients were enrolled onto the study and 535 were treated .  Median overall survival was 5.8 months for gemcitabine/bevacizumab and 5.9 months for gemcitabine/placebo ( P = .95 ) . Median progression-free survival was 3.8 and 2.9 months , respectively ( P = .07 ) . Overall response rates were 13 % and 10 % , respectively . Patients with a performance status of 0 , 1 , and 2 survived a median of 7.9 , 4.8 , and 2.4 months , respectively . The only statistically significant differences in grade s 3 and 4 toxicity occurred for hypertension ( 10 % v 3 % ; P < .001 ) and proteinuria ( 5 % v 1 % ; P = .002 ) ; venous thrombosis grade > or = 3 was equivalent in both arms ( 14 % and 15 % , respectively ) . CONCLUSION The addition of bevacizumab to gemcitabine does not improve survival in advanced pancreatic cancer patients PURPOSE Gemcitabine is generally considered to constitute first-line therapy for pancreatic cancer . To determine whether the addition of fluorouracil ( 5-FU ) improves on the results from single-agent gemcitabine , the Eastern Cooperative Oncology Group ( ECOG ) compared gemcitabine plus bolus 5-FU with gemcitabine alone for patients with advanced pancreatic carcinoma . PATIENTS AND METHODS This trial involved patients with biopsy-proven , advanced carcinoma of the pancreas not amenable to surgical resection . Patients were r and omized to receive either gemcitabine alone ( 1,000 mg/m(2)/wk ) weekly for 3 weeks of every 4 or to receive gemcitabine ( 1,000 mg/m(2)/wk ) followed by 5-FU ( 600 mg/m(2)/wk ) weekly on the same schedule . The primary end point of the trial was survival , with secondary end points of time to progression and response rate . RESULTS Of 327 patients enrolled over 18 months , 322 were eligible . Overall , the median survival was 5.4 months for gemcitabine alone and 6.7 months for gemcitabine plus 5-FU ( P = .09 ) . Progression-free survival for gemcitabine alone was 2.2 months , compared with 3.4 months for gemcitabine plus 5-FU ( P = .022 ) . Objective responses were uncommon and were observed in only 5.6 % of patients treated with gemcitabine and 6.9 % of patients treated with gemcitabine plus 5-FU . Most toxicities were hematologic or gastrointestinal ; no significant differences were noted between the two treatment arms . CONCLUSION 5-FU , administered in conjunction with gemcitabine , did not improve the median survival of patients with advanced pancreatic carcinoma compared with single-agent gemcitabine . Further studies with other combinations of gemcitabine and 5-FU are not compelling , and clinical trial re sources should address other combinations and novel agents BACKGROUND Annualised figures show an up to 7-fold higher incidence of vascular thromboembolism ( VTE ) in patients with advanced pancreatic cancer ( APC ) compared to other common malignancies . Concurrent VTE has been shown to confer a worse overall prognosis in APC . METHODS One hundred and twenty three APC patients were r and omised to receive either gemcitabine 1000 mg/m(2 ) or the same with weight-adjusted dalteparin ( WAD ) for 12 weeks . Primary end-point was the reduction of all-type VTE during the study period . NCT00462852 , IS RCT N : 76464767 . FINDINGS The incidence of all-type VTE during the WAD treatment period ( < 100 days from r and omisation ) was reduced from 23 % to 3.4 % ( p = 0.002 ) , with a risk ratio (RR)of 0.145 , 95 % confidence interval ( CI ) ( 0.035 - 0.612 ) and an 85 % risk reduction . All-type VTE throughout the whole follow-up period was reduced from 28 % to 12 % ( p = 0.039 ) , RR = 0.419 , 95 % CI ( 0.187 - 0.935 ) and a 58 % risk reduction . Lethal VTE < 100 days was seen only in the control arm , 8.3 % compared to 0 % ( p = 0.057 ) , RR = 0.092 , 95 % CI ( 0.005 - 1.635 ) . INTERPRETATION Weight adjusted dalteparin used as primary prophylaxis for 12 weeks is safe and produces a highly significant reduction of all-type VTE during the prophylaxis period . The benefit is maintained after dalteparin withdrawal although decreases with time PURPOSE Patients with advanced pancreas cancer present with disease that is poorly responsive to conventional therapies . Pre clinical and early clinical evidence has supported targeting the epidermal growth factor receptor ( EGFR ) signaling pathway in patients with pancreas cancer . This trial was conducted to evaluate the contribution of an EGFR-targeted agent to st and ard gemcitabine therapy . Cetuximab is a monoclonal antibody against the lig and -binding domain of the receptor . PATIENTS AND METHODS Patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma were r and omly assigned to receive gemcitabine alone or gemcitabine plus cetuximab . The primary end point was overall survival . Secondary end points included progression-free survival , time to treatment failure , objective response , and toxicity . RESULTS A total of 745 eligible patients were accrued . No significant difference was seen between the two arms of the study with respect to the median survival time ( 6.3 months for the gemcitabine plus cetuximab arm v 5.9 months for the gemcitabine alone arm ; hazard ratio = 1.06 ; 95 % CI , 0.91 to 1.23 ; P = .23 , one-sided ) . Objective responses and progression-free survival were similar in both arms of the study . Although time to treatment failure was longer in patients on gemcitabine plus cetuximab ( P = .006 ) , the difference in length of treatment was only 2 weeks longer in the combination arm . Among patients who were studied for tumoral EGFR expression , 90 % were positive , with no treatment benefit detected in this patient subset . CONCLUSION In patients with advanced pancreas cancer , the anti-EGFR monoclonal antibody cetuximab did not improve the outcome compared with patients treated with gemcitabine alone . Alternate targets other than EGFR should be evaluated for new drug development PURPOSE TNFerade biologic is a novel means of delivering tumor necrosis factor alpha to tumor cells by gene transfer . We herein report final results of the largest r and omized phase III trial performed to date among patients with locally advanced pancreatic cancer ( LAPC ) and the first to test gene transfer against this malignancy . PATIENTS AND METHODS In all , 304 patients were r and omly assigned 2:1 to st and ard of care plus TNFerade ( SOC + TNFerade ) versus st and ard of care alone ( SOC ) . SOC consisted of 50.4 Gy in 28 fractions with concurrent fluorouracil ( 200 mg/m(2 ) per day continuous infusion ) . TNFerade was injected intratumorally before the first fraction of radiotherapy each week at a dose of 4 × 10(11 ) particle units by using either a percutaneous transabdominal or an endoscopic ultrasound approach . Four weeks after chemoradiotherapy , patients began gemcitabine ( 1,000 mg/m(2 ) intravenously ) with or without erlotinib ( 100 to 150 mg per day orally ) until progression or toxicity . RESULTS The analysis included 187 patients r and omly assigned to  SOC + TNFerade  and  90 to SOC  by using a modified intention-to-treat approach . Median follow-up was 9.1 months ( range , 0.1 to 50.5 months ) . Median survival was 10.0 months for patients in both the SOC + TNFerade and SOC arms ( hazard ratio [ HR ] , 0.90 ; 95 % CI , 0.66 to 1.22 ; P = .26 ) . Median progression-free survival ( PFS ) was 6.8 months for SOC + TNFerade versus 7.0 months for SOC ( HR , 0.96 ; 95 % CI , 0.69 to 1.32 ; P = .51 ) . Among patients treated on the SOC + TNFerade arm , multivariate analysis showed that TNFerade injection by an endoscopic ultrasound-guided transgastric/transduodenal approach rather than a percutaneous transabdominal approach was a risk factor for inferior PFS ( HR , 2.08 ; 95 % CI , 1.06 to 4.06 ; P = .032 ) . The patients in the SOC + TNFerade arm experienced more grade 1 to 2 fever and chills than those in the SOC arm ( P < .001 ) but both arms had similar rates of grade 3 to 4 toxicities ( all P > .05 ) . CONCLUSION SOC + TNFerade  is safe but not effective for prolonging survival in patients with LAPC Abstract : A r and omized , controlled trial was conducted to clarify the effect of novel radiosensitizer , PR-350 , accompanied by intraoperative radiology ( IOR ) on locally advanced pancreatic cancer . Between July 1999 and March 2002 , 48 patients were enrolled in this clinical trial and received either  PR-350 or placebo . Any differences between the PR-350 group ( n = 22 ) and control group ( n = 25 ) were not statically significant . All patients were evaluated , and none of them showed toxicity , with the exception of 1 patient from the control group , and the PR-350 compound was considered to be safe . The efficacy of IOR with PR-350 was evaluated using CT examination . The committee responsible for evaluating efficacy reported that 47.4 % of the PR-350 group showed the effective response , compared with 21.7 % of the control group ( P = 0.1067 , Fisher analysis ) . At 6 months following treatment , the tumor mass reduction rate in the PR-350 group was significantly improved ( P = 0.0274 ) . By the time of the last follow-up in July 2003 , 17 PR-350 patients and 24 control patients group had died of the disease . The median survival period of the PR-350 group was thus 318.5 days and that of the control group is 303.0 days . One-year survival rates of the PR-350 group and control group were 36.4 % and 32.0 % , respectively . Although the PR-350 group did not demonstrate significantly better survival than the control group , 4 of 22 PR-350 patients were still living more than 2 years after the end of the trial , compared with only 1 of 25 patients from the control group . The mechanism of this increased therapeutic response to radiotherapy using PR-350 must be clarified to establish more effective strategy for pancreatic cancer treatment To date , only limited toxicity data are available for the combination of erlotinib with either capecitabine or gemcitabine as front-line therapy for advanced pancreatic cancer . Within a r and omized phase III trial , 281 treatment-naive patients were r and omly assigned between capecitabine ( 2000 mg/m2/day , for 14 days , once every 3 weeks ) plus erlotinib ( 150 mg/day , arm A ) and gemcitabine ( 1000 mg/m2 as a 30-min infusion ) plus erlotinib ( 150 mg/day , arm B ) . In case of treatment failure , patients were crossed over to a second-line treatment with the comparator cytostatic drug without erlotinib . The primary study endpoint was the time to treatment failure of second-line therapy ( TTF2 ) . This interim analysis of toxicity contains safety data from the first 127 r and omized patients . During first-line therapy , patients received a median number of three treatment cycles ( range 0–13 ) in both the arms . Regarding chemotherapy , a treatment delay was observed in 12 % of the cycles in arm A and in 22 % of the cycles in arm B. Dose reductions of the cytostatic drug were performed in 18 and 27 % of treatment cycles , respectively . Erlotinib dose reductions were performed in 6 and 11 % of all cycles . Grade 3/4 hematological toxicity was < 10 % in both the arms ; major grade 3/4 toxicities in arms A and B were diarrhea ( 9 vs. 7 % ) , skin rash ( 4 vs. 12 % ) , and h and –foot syndrome ( 7 vs. 0 % ) . No treatment-related death was observed . In conclusion , this interim safety analysis suggests that treatment with erlotinib 150 mg/day is feasible in combination with capecitabine or gemcitabine PURPOSE Most patients with advanced pancreas cancer experience pain and must limit their daily activities because of tumor-related symptoms . To date , no treatment has had a significant impact on the disease . In early studies with gemcitabine , patients with pancreas cancer experienced an improvement in disease-related symptoms . Based on those findings , a definitive trial was performed to assess the effectiveness of gemcitabine in patients with newly diagnosed advanced pancreas cancer . PATIENTS AND METHODS One hundred twenty-six patients with advanced symptomatic pancreas cancer completed a lead-in period to characterize and stabilize pain and were r and omized to receive either gemcitabine 1,000 mg/m2 weekly x 7 followed by 1 week of rest , then weekly x 3 every 4 weeks thereafter ( 63 patients ) , or to fluorouracil ( 5-FU ) 600 mg/m2 once weekly ( 63 patients ) . The primary efficacy measure was clinical benefit response , which was a composite of measurements of pain ( analgesic consumption and pain intensity ) , Karnofsky performance status , and weight . Clinical benefit required a sustained ( > or = 4 weeks ) improvement in at least one parameter without worsening in any others . Other measures of efficacy included response rate , time to progressive disease , and survival . RESULTS Clinical benefit response was experienced by 23.8 % of gemcitabine-treated patients compared with 4.8 % of 5-FU-treated patients ( P = .0022 ) . The median survival duration s were 5.65 and 4.41 months for gemcitabine-treated and 5-FU-treated patients , respectively ( P = .0025 ) . The survival rate at 12 months was 18 % for gemcitabine patients and 2 % for 5-FU patients . Treatment was well tolerated . CONCLUSION This study demonstrates that gemcitabine is more effective than 5-FU in alleviation of some disease-related symptoms in patients with advanced , symptomatic pancreas cancer .  Gemcitabine also confers a modest survival advantage over treatment with 5-FU PURPOSE Development of new and expensive drugs with activity against pancreatic cancer has made economic considerations more relevant to treatment decision-making for advanced disease . Economic modeling can be used to explore the potential of such novel therapies and to inform clinical trial design . METHODS AND MATERIAL S We developed a Markov model to evaluate the cost-effectiveness of radiation plus fluorouracil ( RT-FU ) relative to no treatment in elderly patients with locally advanced pancreatic cancer ( LAPC ) and to determine the economic potential of radiation plus gemcitabine ( RT-GEM ) , a novel regimen for this disease . We used the SEER-Medicare data base to estimate effectiveness and costs supplemented by data from the literature where necessary . RESULTS Relative to no treatment , RT-FU was associated with a cost-effectiveness ratio ( ICER ) of $ 68,724/QALY in the base case analysis . Compared with RT-FU , the ICER for RT-GEM was below $ 100,000/QALY when the risk of dying with the new regimen was < 85 % than with the st and ard regimen . However , > 1,000 subjects would be necessary to demonstrate this level of efficacy in a r and omized trial . The ICER of RT-GEM was most sensitive to utility values , and , at lower efficacy levels , to costs of gemcitabine and treatment-related toxicity . CONCLUSIONS In elderly patients with LAPC , RT-FU is a cost-effective alternative to no treatment . The novel regimen of RT-GEM is likely to be cost-effective at any clinical ly meaningful benefit , but quality -of-life issues , drug acquisition , and toxicity-related costs may be relevant , especially at lower efficacy levels BACKGROUND Sorafenib is an oral anticancer agent targeting Ras-dependent signaling and angiogenic pathways . A phase I trial demonstrated that the combination of gemcitabine and sorafenib was well tolerated and had activity in advanced pancreatic cancer ( APC ) patients . The BAYPAN study was a multicentric , placebo-controlled , double-blind , r and omized phase III trial comparing gemcitabine/sorafenib and gemcitabine/placebo in the treatment of APC . PATIENTS AND METHODS The patient eligibility criteria were locally advanced or metastatic pancreatic adenocarcinoma , no prior therapy for advanced disease and a performance status of zero to two . The primary end point was progression-free survival ( PFS ) . The patients received gemcitabine 1000 mg/m(2 ) i.v . , weekly seven times followed by 1 rest week , then weekly three times every 4 weeks plus sorafenib 200 mg or placebo , two tablets p.o . , twice daily continuously . RESULTS Between December 2006 and September 2009 , 104 patients were enrolled on the study ( 52 pts in each arm ) and 102 patients were treated . The median and the 6-month PFS were 5.7 months and 48 % for gemcitabine/placebo and 3.8 months and 33 % for gemcitabine/sorafenib ( P = 0.902 , stratified log-rank test ) , respectively . The median overall survivals were 9.2 and 8 months , respectively ( P = 0.231 , log-rank test ) . The overall response rates were similar ( 19 and 23 % , respectively ) . CONCLUSION The addition of sorafenib to gemcitabine does not improve PFS in APC patients Background Stereotactic body radiation therapy ( SBRT ) is a promising option for patients with pancreatic cancer ( PCA ) ; however , limited data support its efficacy . This study review s our institutional experience of SBRT in the treatment of locally advanced ( LAPC ) and borderline resectable ( BRPC ) PCA . Methods Charts of all PCA patients receiving SBRT at our institution from 2010 to 2014 were review ed . Most patients received pre-SBRT chemotherapy . Primary endpoints included overall survival ( OS ) and local progression-free survival ( LPFS ) . Patients received a total dose of 25–33 Gy in five fractions . Results A total of 88 patients were included in the analysis , 74 with LAPC and 14 with BRPC . The median age at diagnosis was 67.2 years , and median follow-up from date of diagnosis for LAPC and BRPC patients was 14.5 and 10.3 months , respectively  . Median OS from date of diagnosis was 18.4 months ( LAPC , 18.4 mo ; BRPC , 14.4 mo ) and median PFS was 9.8 months ( 95 % CI 8.0–12.3 ) . Acute toxicity was minimal with only three patients ( 3.4 % ) experiencing acute grade ≥3 toxicity . Late grade ≥2 gastrointestinal toxicity was seen in five patients ( 5.7 % ) . Of the 19 patients ( 21.6 % ) who underwent surgery , 79 % were LAPC patients and 84 % had margin-negative resections . Conclusions Chemotherapy followed by SBRT in patients with LAPC and BRPC result ed in minimal acute and late toxicity . A large proportion of patients underwent surgical resection despite limited radiographic response to therapy . Further refinements in the integration of chemotherapy , SBRT , and surgery might offer additional advancements toward optimizing patient outcomes PURPOSE To compare protracted venous infusion ( PVI ) fluorouracil ( 5-FU ) with PVI 5-FU plus mitomycin ( MMC ) in patients with advanced pancreatic cancer in a multicenter , prospect ively r and omized study . PATIENTS AND METHODS Two hundred eight patients were r and omized to PVI 5-FU ( 300 mg/m(2)/d for a maximum of 24 weeks ) or  PVI 5-FU plus MMC  ( 7 mg/m(2 ) every 6 weeks for four courses ) . The major end points were tumor response , survival , toxicity , and quality of life ( QOL ) . RESULTS The two treatment groups were balanced for baseline demographic factors , and 62 % had metastatic disease . The overall response rate was 8.4 % ( 95 % confidence interval [ CI ] ) 3.2 % to 13.7 % for patients treated with PVI 5-FU alone compared with 17.6 % ; 95 % CI 10.3 % to 25.1 % for PVI 5-FU plus MMC ( P = .04 ) . Median failure-free survival was 2.8 months for PVI 5-FU and 3.8 months for PVI 5-FU plus MMC ( P = .14 ) . Median survival was 5.1 months for PVI 5-FU and 6.5 months for PVI 5-FU plus MMC ( P = .34 ) . Toxicities in both arms were mild . There was an increased incidence of neutropenia in the 5-FU plus MMC arm ( P < .01 ) , although no differences in infection were seen . No patients developed hemolytic uremic syndrome . Global QOL improved significantly after 24 weeks of treatment compared with baseline for patients receiving 5-FU plus MMC , although there was no statistically significant difference in QOL between arms . CONCLUSION PVI 5-FU plus MMC result ed in a superior response rate in comparison with PVI 5-FU alone in advanced pancreatic cancer , but this did not translate into a survival advantage . These results emphasize the importance of chemotherapy in this setting and the continuing value of the fluoropyrimidines in pancreatic cancer PURPOSE To determine the efficacy and tolerability of gemcitabine (GEM)-concurrent chemoradiotherapy ( CCRT ) vs. 5-fluorouracil ( 5-FU ) CCRT for locally advanced pancreatic cancer . METHODS AND MATERIAL S Thirty-four patients with locally advanced pancreatic cancer were studied . Eighteen patients were r and omized to receive GEM CCRT ( 600 mg/m(2)/wk for 6 weeks ) and 16 patients to receive bolus 5-FU CCRT ( 500 mg/m(2)/d for 3 days repeated every 2 weeks for 6 weeks ) . All patients were to receive 3D-CRT 50.4 - 61.2 Gy at 1.8-Gy/d fractions and GEM ( 1000 mg/m(2 ) weekly for 3 weeks repeated every 4 weeks ) after RT . RESULTS The median survival and median time to progression were 14.5 months and 7.1 months for the GEM CCRT group and 6.7 months and 2.7 months for the 5-FU CCRT group ( p = 0.027 and p = 0.019 , respectively ) . The quality -adjusted life month survival time was 11.2 + /- 0.5 months for GEM CCRT and 6.0 + /- 0.3 months for 5-FU CCRT patients ( p < 0.001 ) . The response rate was 50 % ( four complete responses and five partial responses ) for GEM CCRT and 13 % ( two partial responses ) for 5-FU CCRT ( p = 0.005 ) . Pain control was 39 % for GEM CCRT and 6 % for 5-FU CCRT ( p = 0.043 ) . Grade 3 - 4 neutropenia ( 34 % vs. 19 % ) , thrombocytopenia ( 0 % vs. 7 % ) , nausea ( 33 % vs. 31 % ) , vomiting ( 17 % vs. 19 % ) , hospitalization days per month of survival ( 7.4 + /- 1.7 days vs. 8.0 + /- 1.3 days ) , and full dose of RT received ( 78 % vs. 75 % ) were not significantly different between the GEM CCRT and 5-FU CCRT patients . CONCLUSION GEM CCRT appears more effective than 5-FU CCRT for locally advanced pancreatic cancer and has comparable tolerability Objective : To prospect ively evaluate the additional value of geriatric assessment ( GA ) for predicting surgical outcomes in a cohort of older patients undergoing a pancreaticoduodenectomy ( PD ) for pancreatic tumors . Background : Older patients are less often referred for possible PD . St and ard preoperative assessment s may underestimate the likelihood of significant adverse outcomes . The prospect i ve utility of vali date d GA has not been studied in this group . Methods : PD-eligible patients were enrolled in a prospect i ve outcome study . St and ard preoperative assessment s were recorded . Elements of vali date d GA were also measured , including components of Fried 's model of frailty , the Vulnerable Elders Survey ( VES-13 ) , and the Short Physical Performance Battery ( SPPB ) . All postoperative adverse events were recorded , systematic ally review ed , and grade d using the Clavien-Dindo system by a surgeon blinded to the GA results . Multivariate regression analyses were conducted . Results : Seventy-six older patients underwent a PD . Significant unrecognized vulnerability was identified at the baseline : Fried 's “ exhaustion ” ( 37.3 % ) , SPPB < 10 ( 28.5 % ) , and VES-13 > 3 ( 15.4 % ) . Within 30 days of PD , 46 % experienced a severe complication ( Clavien-Dindo grade ≥III ) . In regression analyses controlling for age , the body mass index , the American Society of Anesthesiologists score , and comorbidity burden , Fried 's “ exhaustion ” predicted major complications [ odds ratio ( OR ) = 4.06 ; P = 0.01 ] , longer hospital stays ( & bgr ; = 0.27 ; P = 0.02 ) , and surgical intensive care unit admissions ( OR = 4.30 ; P = 0.01 ) . Both SPPB ( OR = 0.61 ; P = 0.04 ) and older age predicted discharge to a rehabilitation facility ( OR = 1.1 ; P < 0.05 ) and age correlated with a lower likelihood of hospital readmission ( OR = 0.94 ; P = 0.02 ) . Conclusions : Controlling for st and ard preoperative assessment s , worse scores on GA prospect ively and independently predicted important adverse outcomes  . Geriatric assessment may help identify older patients at high risk for complications from PD Background —Impeded flow of pancreatic juice due to mechanical obstruction of the pancreatic duct in patients with cancer of the pancreatic head region causes exocrine pancreatic insufficiency with steatorrhoea and creatorrhoea . This may contribute to the profound weight loss that often occurs in these patients . Aims —To investigate whether pancreatic enzyme replacement therapy prevents this weight loss . Patients —Twenty one patients with unresectable cancer of the pancreatic head region with suspected pancreatic duct obstruction , a biliary endoprosthesis in situ , and a Karnofsky performance status greater than 60 . Methods —R and omised double blind trial of eight weeks with either placebo or high dose enteric coated pancreatin enzyme supplementation . All patients received dietary counselling . Results —The mean difference in the percentage change of body weight was 4.9 % ( p=0.02 , 95 % confidence interval for the difference : 0.9 to 8.9 ) . Patients on pancreatic enzymes gained 1.2 % ( 0.7 kg ) body weight whereas patients on placebo lost 3.7 % ( 2.2 kg ) . The fat absorption coefficient in patients on pancreatic enzymes improved by 12 % whereas in placebo patients it dropped by 8 % ( p=0.13 , 95 % confidence interval for the difference : –6 to 45 ) . The daily total energy intake was 8.42 MJ in patients on pancreatic enzymes and 6.66 MJ in placebo patients ( p=0.04 , 95 % confidence interval for the difference : 0.08 to 3.44 ) . Conclusions —Weight loss in patients with unresectable cancer of the pancreatic head region and occlusion of the pancreatic duct can be prevented , at least for the period immediately after insertion of a biliary endoprosthesis , by high dose enteric coated pancreatin enzyme supplementation in combination with dietary counselling BACKGROUND AND PURPOSE The majority of patients with pancreatic cancer have advanced disease at the time of diagnosis and are not amenable for surgery . Stereotactic radiotherapy ( SRT ) may be an alternative treatment for patients with locally advanced disease . The effect of SRT was investigated in the present phase-II trial . PATIENTS AND METHODS Twenty-two patients with locally advanced and surgically non-resectable , histological proven pancreatic carcinoma were included into the trial . The patients were immobilized by the Elekta stereotactic body frame ( SBF ) or a custom made body frame . SRT was given on st and ard LINAC with st and ard multi-leaf collimator . Central dose was 15 Gyx3 within 5 - 10 days . RESULTS Evaluation of response was found to be very difficult due to radiation and tumour related tissue reaction . Only two patients ( 9 % ) were found to have a partial response ( PR ) , the remaining had no change ( NC ) or progression ( PD ) after treatment . Six patients had local tumour progression , but only one patient had an isolated local failure without simultaneous distant metastasis . Median time to local or distant progression was 4.8 months . Median survival time was 5.7 months and only 5 % were alive 1 year after treatment . Acute toxicity reported 14 days after treatment was pronounced . There was a significant deterioration of performance status ( P=0.008 ) , more nausea ( P=0.001 ) and more pain ( P=0.008 ) after 14 days compared with base-line . However , 8 of 12 patients ( 66 % ) improved in performance status , scored less nausea , pain , or needed less analgesic drugs at 3 months after treatment . Four patients suffered from severe mucositis or ulceration of the stomach or duodenum and one of the patients had a non-fatal ulcer perforation of the stomach . CONCLUSIONS SRT was associated with poor outcome , unacceptable toxicity and question able palliative effect and can not be recommended for patients with advanced pancreatic carcinoma PURPOSE The median survival time of patients with locally advanced adenocarcinoma of the pancreas is 8 - 10 months . Radiation therapy has been used to improve local control and palliate symptoms . This r and omized study was undertaken to determine whether the addition of 5-fluorouracil ( 5-FU ) and mitomycin-C ( MMC ) to radiation therapy improves outcome in this patient population . PATIENTS AND METHODS One hundred fourteen patients were r and omized to receive 59.4 Gy external beam radiotherapy in 1.8 Gy fractions alone or in combination with 5-FU ( 1,000 mg/m2/day for 4 days by continuous infusion Days 2 - 5 and 28 - 31 ) and MMC ( 10 mg/m2 on Day 2 ) . RESULTS One hundred four patients were evaluable for efficacy . Hematologic and nonhematologic toxicities were more common in the combination arm . The response rates were 6 % in the radiation therapy arm and 9 % in the combination arm . There were no differences in median disease-free survival time ( DFS ) or overall survival time ( OS ) between the combination and radiation therapy alone arms : 5.1 vs. 5.0 months , respectively , for DFS ( p = 0.19 ) and 8.4 vs. 7.1 months , respectively , for OS ( p = 0.16 ) . CONCLUSION The addition of 5-FU and MMC to radiotherapy increased toxicity without improving DFS or OS in patients with locally advanced pancreatic cancer . Alternative drugs for radiosensitization may improve outcome PURPOSE Single-agent gemcitabine became st and ard first-line treatment for advanced pancreatic cancer after demonstration of superiority compared with fluorouracil . The Gruppo Italiano Pancreas 1 r and omized phase III trial aim ed to compare gemcitabine plus cisplatin versus gemcitabine alone ( Clinical Trials.gov ID NCT00813696 ) . PATIENTS AND METHODS Patients with locally advanced or metastatic pancreatic cancer , age 18 to 75 years , and Karnofsky performance status ( KPS ) > or = 50 , were r and omly assigned to receive gemcitabine ( arm A ) or gemcitabine plus cisplatin ( arm B ) . Arm A : gemcitabine 1,000 mg/m(2 ) weekly for 7 weeks , and , after a 1-week rest , on days 1 , 8 , and 15 every 4 weeks . Arm B : cisplatin 25 mg/m(2 ) added weekly to gemcitabine , except cycle 1 day 22 . Primary end point was overall survival . To have 8 % power of detecting a 0.74 hazard ratio ( HR ) of death , with bilateral alpha .05 , 355 events were needed and 400 patients planned . RESULTS Four hundred patients were enrolled ( arm A : 199 ; arm B : 201 ) . Median age was 63 , 59 % were male , 84 % had stage IV , and 83 % had KPS > or = 80 .  Median overall survival was 8.3 months versus 7.2 months in arm A and B , respectively ( HR , 1.10 ; 95 % CI , 0.89 to 1.35 ; P = .38 ) . Median progression-free survival was 3.9 months versus 3.8 months in arm A and B , respectively ( HR , 0.97 ; 95 % CI , 0.80 to 1.19 ; P = .80 ) . The objective response rate was 10.1 % in A and 12.9 % in B ( P = .37 ) . Clinical benefit was experienced by 23.0 % in A and 15.1 % in B ( P = .057 ) . Combination therapy produced more hematologic toxicity , without relevant differences in nonhematologic toxicity . CONCLUSION The addition of weekly cisplatin to gemcitabine failed to demonstrate any improvement as first-line treatment of advanced pancreatic cancer PURPOSE To compare the effectiveness and tolerability of gemcitabine plus cisplatin with single-agent gemcitabine as first-line chemotherapy for locally advanced or metastatic pancreatic cancer . PATIENTS AND METHODS Patients with advanced adenocarcinoma of the pancreas were r and omly assigned to receive either gemcitabine 1,000 mg/m2 and cisplatin 50 mg/m2 given on days 1 and 15 of a 4-week cycle ( GemCis arm ) or gemcitabine alone at a dose of 1,000 mg/m2 on days 1 , 8 , and 15 of a 4-week regimen ( Gem arm ) . The primary end point was overall survival ; secondary end points were progression-free survival , response rate , safety , and quality of life . RESULTS One hundred ninety-five patients were enrolled and showed baseline characteristics well balanced between treatment arms . Combination treatment in the GemCis arm was associated with a prolonged median progression-free survival ( 5.3 months v 3.1 months ; hazard ratio [ HR ] = 0.75 ; P = .053 ) . Also , median overall survival was superior for patients treated in the GemCis arm as compared with the Gem arm ( 7.5 v 6.0 months ) , an advantage which did not , however , reach statistical significance ( HR = 0.80 ; P = .15 ) . Tumor response rates were comparable between treatment arms ( 10.2 % v 8.2 % ) . The rate of stable disease was , however , greater in the combination arm ( 60.2 % v 40.2 % ; P < .001 ) . Grade 3 to 4 hematologic toxicity did not exceed 15 % in both treatment arms . CONCLUSION These results support the efficacy and safety of an every-2-weeks treatment with gemcitabine plus cisplatin .  Median overall survival and progression-free survival were more favorable in the combination arm as compared with gemcitabine alone , although the difference did not attain statistical significance BACKGROUND The role of chemoradiation with systemic chemotherapy compared with chemotherapy alone in locally advanced pancreatic cancer ( LAPC ) is uncertain . PATIENTS AND METHODS One hundred and nineteen patients with LAPC , World Health Organization performance status of zero to two were r and omly assigned to either the induction CHRT group ( 60 Gy , 2 Gy/fraction ; concomitant 5-fluorouracil infusion , 300 mg/m(2)/day , days 1 - 5 for 6 weeks ; cisplatin , 20 mg/m(2)/day , days 1 - 5 during weeks 1 and 5 ) or the induction gemcitabine group ( GEM : 1000 mg/m(2 ) weekly for 7 weeks ) . Maintenance gemcitabine ( 1000 mg/m(2 ) weekly , 3/4 weeks ) was given in both arms until disease progression or toxicity . RESULTS Overall survival was shorter in the CHRT than in GEM arm [ median survival 8.6 ( 99 % confidence interval 7.1 - 11.4 ) and 13 months ( 8.7 - 18.1 ) , P = 0.03 ] . One-year survival was , respectively , 32 % and 53 % . These results were confirmed in a per- protocol analysis for patients who received 75 % or more of the planned dose of radiotherapy . More overall grade s 3 - 4 toxic effects were recorded in the CHRT arm , both during induction ( 36 versus 22 % ) and maintenance ( 32 versus 18 % ) . CONCLUSION This intensive induction schedule of CHRT was more toxic and less effective than gemcitabine alone Objective AIO-PK0104 investigated two treatment strategies in advanced pancreatic cancer ( PC ) : a reference sequence of gemcitabine/erlotinib followed by 2nd-line capecitabine was compared with a reverse experimental sequence of capecitabine/erlotinib followed by gemcitabine . Methods 281 patients with PC were r and omly assigned to 1st-line treatment with either gemcitabine plus erlotinib or capecitabine plus erlotinib . In case of treatment failure ( eg , disease progression or toxicity ) , patients were allocated to 2nd-line treatment with the comparator cytostatic drug without erlotinib . The primary study endpoint was time to treatment failure ( TTF ) after 1st- and 2nd-line therapy ( TTF2 ; non-inferiority design ) . KRAS exon 2 mutations were analysed in archival tumour tissue from 173 of the r and omised patients . Results Of the 274 eligible patients , 43 had locally advanced and 231 had metastatic disease ; 140 ( 51 % ) received 2nd-line chemotherapy .  Median TTF2 was estimated with 4.2 months in both arms ; median overall survival was 6.2 months with gemcitabine/erlotinib followed by capecitabine and 6.9 months with capecitabine/erlotinib followed by gemcitabine , respectively ( HR 1.02 , p=0.90 ) . TTF for 1st-line therapy ( TTF1 ) was significantly prolonged with gemcitabine/erlotinib compared to capecitabine/erlotinib ( 3.2 vs 2.2 months ; HR 0.69 , p=0.0034 ) . Skin rash was associated with both TTF2 ( rash grade 0/1/2–4:2.9/4.3/6.7 months , p<0.0001 ) and survival ( 3.4/7.0/9.6 months , p<0.0001 ) . Each arm showed a safe and manageable toxicity profile during 1st- and 2nd-line therapy . A KRAS wild-type status ( 52/173 patients , 30 % ) was associated with an improved overall survival ( HR 1.68 , p=0.005 ) . Conclusion Both treatment strategies are feasible and demonstrated comparable efficacy ; KRAS may serve as biomarker in patients with advanced PC treated with erlotinib . Trial registration number This study was registered at Clinical Trials.gov , number NCT00440167 . Significance of this study What is already known on this subject ? Gemcitabine-based chemotherapy remains an international st and ard of care for patients with non-resectable , advanced pancreatic cancer ( PC ) .  Anti-EGFR treatment with the tyrosine kinase inhibitor erlotinib , as well as chemotherapy intensification by application of the FOLFIRINOX regimen , both significantly improved overall survival in r and omised phase 3 trials . The optimal ( sequential ) regimen for the use of gemcitabine , erlotinib and the oral fluoropyrimidine capecitabine remains unclear in advanced PC . Molecular predictors for the efficacy of anti-EGFR treatments in PC have not been defined up to now . What are the new findings ? The sequential use of gemcitabine , erlotinib and capecitabine is safe and equally effective in PC ; gemcitabine appears to be more effective in 1st- and 2nd-line therapy than capecitabine and therefore remains the preferred combination partner for erlotinib .  Skin rash is strongly correlated with efficacy outcome measures in PC patients treated with erlotinib . KRAS wild-type status appears to be associated with improved overall survival in patients treated with erlotinib in this AIO study . Significance of this study How might it impact on clinical practice in the foreseeable future ? The benefit of adding erlotinib to chemotherapy is restricted to patients that experience skin rash during treatment ; non-rash patients are characterised by a very poor outcome and need to be offered novel treatment strategies . Second-line salvage chemotherapy is effective and safe in selected PC patients . KRAS could serve as the first biomarker for improved survival in erlotinib-treated patients ; the predictive value of KRAS for erlotinib efficacy remains to be defined prospect ively
target: Initial systemic chemotherapy ( 6 months ) with a combination regimen is recommended for most patients ( for some patients radiation therapy may be offered up front ) with Eastern Cooperative Oncology Group performance status 0 or 1 and a favorable comorbidity profile .
  There is no clear evidence to support one regimen over another .
background: PURPOSE To provide evidence -based recommendations to oncologists and others for treatment of patients with locally advanced , unresectable pancreatic cancer .