***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 Background / purpose S-1 is a new oral fluoropyrimidine anticancer agent shown to be effective for pancreatic cancer . In a previous phase I trial , we evaluated the safety of S-1 combined with radiotherapy to determine the maximum tolerated dose and dose-limiting toxicity in patients with unresectable pancreatic cancer . The recommended dose of S-1 for phase II trials of chemoradiotherapy was determined as 80 mg/m2/day given on days 1–21 of a 28-day cycle . This phase II study was conducted to further evaluate the efficacy and toxicity of radiotherapy combined with S-1 ( UMIN000004794 ) . Methods Eligible patients had locally advanced and unresectable pancreatic cancer without distant metastases , an Eastern Cooperative Oncology Group performance status of 0–1 , adequate organ and marrow functions , and no prior anticancer therapy . Patients initially received 4 weeks of chemoradiotherapy . S-1 was given orally at a dose of 80 mg/m2/day twice daily on days 1–21 . Radiotherapy was delivered in fractions of 1.25 Gy twice daily , 5 days per week for 4 weeks ( total dose : 50 Gy in 40 fractions ) . One month after the completion of chemoradiotherapy , S-1 was administered for 14 days followed by a 14-day rest period . This cycle was repeated as maintenance therapy until disease progression or unacceptable toxicity . Results Fifty patients were enrolled in this phase II study . Median follow-up was 14.6 months ( range 5.4–58.9 months ) . Forty-three patients ( 86 % ) completed the scheduled course of chemoradiotherapy . There was no treatment-related death or grade 4 toxicity . The major toxic effects were leukopenia and nausea . The objective tumor response according to the Response Evaluation Criteria in Solid Tumours criteria was partial response in 15 patients ( 30 % ) ( 95 % confidence interval ( CI ) , 18–45 % ) , stable disease in 23 ( 46 % ) , and progressive disease in 12 ( 24 % ) . Median progression-free survival and median overall survival were 6.7 months ( 95 % CI , 4.7–11.2 months ) and 14.3 months ( 95 % CI , 10.8–20.8 months ) , respectively . Survival rates at 1 and 2 years were 62 and 27 % , respectively . Conclusions Combination therapy with S-1 and radiation in patients with locally advanced and unresectable pancreatic cancer is considered a promising , well-tolerated regimen that can be recommended as an effective treatment for locally advanced pancreatic cancer Objective A Phase II study was conducted at Indiana University to evaluate the safety and efficacy of combined weekly Gemcitabine ( GEM ) with external beam radiotherapy ( RT ) in unresectable , locally advanced pancreatic cancer ( LAPC ) . Methods Eligible patients had biopsy-proven LAPC without evidence of metastatic disease . In part A of the treatment plan , patients received GEM 600 mg/m2 IV weekly , with concurrent RT ( 50.4 Gy in 28 fractions , 1.8 Gy/d , 5 days per week ) . Part B of the treatment plan began approximately 4 weeks after completing part A : patients without disease progression received weekly GEM 1000 mg/m2 on days 1 , 8 , and 15 of a 28-day cycle for 6 cycles or until disease progression . Results From April 2001 to June 2003 , of 28 patients evaluated , 24 ( 86 % ) completed part A. About 22 patients had grade 3 toxicities , primarily hematologic ( 43 % ) and gastrointestinal ( 36 % ) . Three patients ( 11 % ) had grade 4 toxicities ( one each for hyperbilirubinemia , infection , and dyspnea ) . The median follow-up was 10 months ( 1–63 months ) for all enrolled patients . Six patients ( 21 % ) had a radiologic partial response , 16 ( 57 % ) had stable disease , 5 ( 18 % ) had progressive disease , and 1 patient ( 4 % ) had an unevaluable response at last follow-up . Four patients ( 14 % ) underwent surgical resection ( 2 with R0 resection ) . Median time to progression was 6 months ( 0–36 months ) . Median survival time was 10.3 months ( 95 % confidence interval , 7.9–14.6 months ) . The 1- and 2-year actuarial survival rates were 30 % and 11 % . At last analysis , all but 2 patients died . Conclusion The activity and toxicity profile of combination GEM and RT indicates that this can be safely administered for patients with LAPC Purpose : The objectives of this phase II study were to evaluate the effect of radiation ( XRT ) on thymidine phosphorylase ( TP ) , dihydropyrimidine dehydrogenase ( DPD ) , and tumor necrosis factor-&agr ; ( TNF-&agr ; ) and the efficacy of capecitabine-XRT in patients with locally advanced pancreatic cancer . Patients and Methods : Twenty patients received 50.4 Gy XRT with capecitabine 1,600 mg/m2 on Monday through Friday for 6 weeks determined from our phase I study ( Saif MW , Eloubeidi MA , Russo S , et al. J Clin Oncol . 2005;23:8679–8687 ) . After capecitabine-XRT , stable and responding patients received capecitabine 2,000 mg/m2 for 14 days every 3 weeks till progression . Restaging was performed every 9 weeks . Tumor specimens were procured with endoscopic ultrasound-fine needle aspiration before and at week 2 after capecitabine-XRT was started to evaluate the effect of XRT on TP , DPD , and TNF-&agr ; mRNA levels , determined by reverse transcriptase-polymerase chain reaction . Results : Among 20 patients , 4 ( 20 % ) had a partial response and 13 ( 65 % ) had stable disease . Two patients underwent surgical resection ( 10 % ) . The 6-month survival rate was 84 % , and the 1-year survival was 58 % . Grade ≥3 toxicities included nausea/vomiting ( 5 % ) , thrombosis ( 5 % ) , hyperbilirubinemia ( 5 % ) , and grade 3 gastrointestinal bleeding ( 5 % ) . TP was elevated during week 2 when compared with the pre-XRT TP ( P = 0.01 ) . However , no such effect of XRT was found either on DPD ( P = 0.22 ) or on TNF-&agr ; ( P = 0.6 ) . No correlation between TP and TNF-&agr ; was noticed . Also , no association between TP/DPD ratio and efficacy of capecitabine was identified . Conclusions : This phase II study further confirms our phase I results and suggests that capecitabine-XRT is an effective , tolerable , and convenient alternative to an infusional 5-fluorouracil regimen for patients with pancreatic cancer . Although results support the use of capecitabine-XRT and TP was up-regulated , there appears to be additional genes associated with the response to capecitabine We evaluated safety and efficacy of concurrent chemoradiotherapy ( CCRT ) with capecitabine in patients with locally advanced pancreatic cancer ( LAPC ) . Between January 2004 and January 2008 , 39 patients with LAPC treated with capecitabine CCRT were review ed .  Capecitabine was administered at 850 mg/m2 twice daily every day with 5 days per week radiotherapy ( 1.8 Gy fractions ) over the 5 weeks . Thirty-seven ( 94.8 % ) patients completed CCRT . Of the 36 evaluable patients , 15 ( 41.7 % ) and 13 ( 36.1 % ) patients achieved partial response and stable disease , and eight ( 28.6 % ) among them received gemcitabine-based post-CCRT chemotherapy without dose reduction or delay . The overall survival was 14.3 months [ 95 % confidence interval ( CI ) : 10.6–17.9 months ] . Median progression-free survival was 11.1 months for all patients , and 7.9 months for those patients who had not received post-CCRT chemotherapy . Eight patients ( 21.6 % ) had severe grade 3 toxicities , seven ( 18.9 % ) 
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Additionally , comparable efficacy was found between capecitabine and GEM-based chemoradiotherapy in terms of OS , PFS , and ORR .
As for grade 3 and 4 acute toxicity , oral FU plus RT significantly reduced the risk of developing hematologic toxicities , nausea , and vomiting when compared to GEM plus RT ( P<0.001 ) .
Oral FU plus RT may be a safe and feasible regimen for patients with LAPC , with similar efficacy and low rate of toxicities compared with GEM plus RT .