_:b517018977 . . _:b517018976 . . _:b517018979 . . . _:b517018978 . . _:b517018989 . _:b21217013 . _:b517018988 . _:b517018991 . _:b517018792 . _:b517018713 . . _:b21217051 "That trial,>>7<< in which patients were randomly assigned to receive either gemcitabine alone or gemcitabine with radiotherapy (50\u00B74 Gy in 28 fractions), was stopped early because of poor recruitment, with 71 patients entered from eight US centres." . _:b517018990 . . _:b517018985 . _:b21217043 . . . _:b517018984 . . _:b517018830 . _:b517018987 . _:b517018717 . _:b517018986 . _:b517018666 . . _:b21217025 _:b21217026 . _:b517018997 . _:b517018901 . _:b21217025 _:b21217027 . _:b517018840 . _:b21217025 _:b21217028 . _:b21217025 _:b21217029 . _:b517019033 . . _:b517018996 . _:b21217025 _:b21217030 . . _:b21217025 _:b21217031 . _:b21217025 _:b21217032 . _:b21217025 _:b21217033 . _:b21217025 _:b21217034 . _:b517018999 . . _:b21217025 _:b21217035 . _:b21217025 _:b21217036 . _:b21217025 _:b21217037 . _:b21217025 _:b21217038 . _:b517018998 . _:b21217025 _:b21217039 . _:b21217025 _:b21217040 . . _:b21217025 _:b21217041 . . _:b517018993 . _:b21217025 _:b21217042 . _:b21217025 _:b21217043 . _:b21217025 _:b21217044 . _:b21217025 _:b21217045 . _:b21217025 _:b21217046 . _:b517019048 . _:b517018992 . _:b21217025 _:b21217047 . _:b21217025 _:b21217048 . . _:b21217025 _:b21217049 . _:b21217025 _:b21217050 . _:b517018995 . _:b517018838 . _:b21217025 _:b21217051 . . _:b21217025 _:b21217052 . _:b21217025 _:b21217053 . _:b21217025 _:b21217054 . _:b517018994 . _:b21217025 _:b21217055 . _:b517018911 . _:b517019005 . . _:b517018658 "23"^^ . _:b517018663 "12"^^ . _:b517019004 . _:b517018967 . _:b517019039 . _:b517018662 "12"^^ . _:b517019007 . _:b517018918 . _:b517019006 . _:b517018659 "21"^^ . _:b21217050 "In phase 1\u20132 clinical trials, once-per-week doses of gemcitabine have ranged from 250 mg/m2 to 1000 mg/m2, and the only phase 3 trial>>7<< to use gemcitabine as a radiosensitiser used a dose of 600 mg/m2." . _:b517018658 . _:b517018900 . _:b517018761 . _:b517019001 . _:b517018657 "25"^^ . _:b517019034 . . _:b517019000 . . . _:b517018984 . _:b517018660 "20"^^ . _:b517019003 . _:b517018661 "17"^^ . _:b517019014 . _:b517018880 . _:b517019002 . . . _:b517019013 . . . _:b517019012 . _:b517018670 "9"^^ . _:b517018671 "8"^^ . _:b517019015 . . _:b517019014 . _:b517019042 . _:b517018668 "10"^^ . . _:b517019009 . _:b517018669 "9"^^ . _:b517018667 "10"^^ . . . _:b517019008 . _:b517018666 "10"^^ . _:b517019011 . _:b517018665 "12"^^ . _:b517019010 . _:b21217044 "However, the overall median survival of all registered patients was 12\u00B77 months (95% 11\u00B70\u201314\u00B75), which is better than previous outcomes in chemotherapy-only studies (roughly 10 months).4, >>5<<" . . _:b21217049 . _:b517018664 "12"^^ . _:b517019021 . _:b517018806 . _:b517018678 "7"^^ . . _:b517019020 . . . _:b517018679 "7"^^ . _:b517019023 . _:b517018676 "7"^^ . _:b517018952 . . _:b517019022 . _:b517018677 "7"^^ . _:b517019017 . . . . _:b517018674 "8"^^ . _:b517019016 . . _:b517018675 "7"^^ . _:b517019019 . . _:b517018879 . _:b517018672 "8"^^ . _:b517019018 . . _:b517019029 . _:b517018673 "8"^^ . _:b517018871 . _:b517018686 "6"^^ . _:b517019028 . _:b517018887 . _:b517018687 "6"^^ . _:b517019031 . _:b517018684 "6"^^ . _:b517018673 . _:b517019030 . _:b517018685 "6"^^ . _:b517019025 . _:b517018935 . _:b517018663 . _:b517018682 "6"^^ . _:b517018674 . . _:b517019024 . _:b517018683 "6"^^ . _:b517019027 . _:b517018680 "6"^^ . _:b517019032 . . _:b517018749 . _:b517019026 . _:b517018681 "6"^^ . _:b517018941 . _:b517019002 . _:b517019037 . . _:b517018937 . _:b517019036 . _:b517018693 "5"^^ . _:b517018886 . _:b517018953 . _:b517019039 . . _:b517018692 "5"^^ . _:b517018752 . _:b517018722 . _:b21217016 "3, 18 Three randomised, controlled trials19, 20, >>21<< with small numbers of patients have compared fluorouracil with gemcitabine chemoradiotherapy as primary treatment for locally advanced pancreatic cancer; one19 showed a significant overall survival benefit for gemcitabine-based treatment," . _:b517019038 . _:b517018695 "5"^^ . . _:b517018748 . . _:b517019033 . _:b517018694 "5"^^ . _:b517018690 "6"^^ . _:b517019032 . _:b21217009 "9, 12, 13, 14, >>15<<, 16, 17 The international, randomised, phase 3 study LAP-07 (NCT00634725), which is comparing chemoradiotherapy with chemotherapy, is expected to be reported in 2013." . _:b517019035 . . _:b517018688 "6"^^ . _:b21217046 "Of the previous studies that compared gemcitabine-based and fluorouracil-based chemoradiotherapy,19, >>20<<, 21 at least one study19 and a meta-analysis22 suggested better survival outcomes with gemcitabine." . _:b517019034 . _:b517018691 "5"^^ . _:b517018689 "6"^^ . . _:b517019045 . . _:b517018917 . _:b517019044 . _:b517018701 "5"^^ . . _:b517019047 . _:b517018700 "5"^^ . _:b21217048 "Of the previous studies that compared gemcitabine-based and fluorouracil-based chemoradiotherapy,19, 20, 21 at least one study>>19<< and a meta-analysis22 suggested better survival outcomes with gemcitabine. However these studies used chemoradiotherapy without induction chemotherapy and were done in unselected patients." . _:b517018720 . _:b517019046 . _:b517018703 "5"^^ . _:b517018764 . _:b21217029 . _:b517018740 . _:b517019041 . _:b517018702 "5"^^ . _:b517019040 . _:b517018697 "5"^^ . . _:b517019043 . _:b517018696 "5"^^ . . _:b517019042 . _:b517018699 "5"^^ . _:b517019053 . _:b517018698 "5"^^ . . _:b21217031 "This meta-analysis included one additional randomised trial26 that was not identified in the original PubMed search, and therefore included three randomised trials and one retrospective comparative study,>>20<< with a total of 229 patients." . _:b517019052 . _:b517018709 "5"^^ . _:b21217044 . . _:b517018708 "5"^^ . . _:b517018711 "4"^^ . _:b21217022 . _:b21217028 "We identified two randomised trials19, 21 that compared gemcitabine-based with fluorouracil-based chemoradiotherapy and one>>25<< that compared gemcitabine-based with paclitaxel-based chemoradiotherapy." . . _:b517019049 . _:b517018710 "5"^^ . . _:b517019048 . _:b517018705 "5"^^ . _:b21217032 . _:b517018854 . _:b517019051 . _:b517018704 "5"^^ . . _:b517019050 . _:b517018707 "5"^^ . _:b517018706 "5"^^ . . . . _:b517018717 "4"^^ . _:b517018716 "4"^^ . . . "PMC0" . . _:b517018831 . _:b517018719 "4"^^ . . _:b517019020 . . _:b517019021 . _:b517019022 . _:b517018718 "4"^^ . _:b517019023 . _:b517019016 . _:b517019017 . _:b517019018 . _:b517018693 . _:b517018713 "4"^^ . _:b517019019 . _:b517019012 . . _:b517019013 . _:b517018672 . _:b517019014 . _:b517018686 . _:b517018712 "4"^^ . _:b517019015 . . . _:b517019008 . _:b517019009 . _:b517019010 . _:b517018715 "4"^^ . _:b517019011 . _:b21217025 "discussion" . _:b517019036 . _:b517019037 . _:b21217024 . _:b517019038 . _:b517018714 "4"^^ . _:b517019039 . _:b517019032 . _:b517019031 . _:b517019033 . _:b517019034 . _:b517018725 "4"^^ . _:b517019035 . _:b517019028 . _:b517019029 . _:b517019030 . _:b517018724 "4"^^ . _:b517019031 . . _:b517019024 . _:b517018665 . _:b517019025 . _:b517019026 . _:b517018727 "4"^^ . _:b517019027 . _:b517019052 . . _:b517019053 . _:b21217054 "caused by a reduction in systemic therapy in the gemcitabine group would be consistent with evidence that systemic therapy is important in the management of locally advanced pancreatic cancer, as was shown by Chauffert and colleagues,>>7<< in whose study compromise in the systemic adjuvant chemotherapy after primary fluorouracil and cisplatin-based chemoradiotherapy resulted in a poor outcome compared with chemotherapy alone." . _:b517018726 "4"^^ . _:b517019048 . _:b517019049 . _:b517018694 . _:b517018721 "4"^^ . _:b517019050 . _:b517019051 . _:b517019044 . _:b517019045 . _:b517019020 . . _:b517019046 . _:b517018720 "4"^^ . _:b517019047 . _:b517019040 . _:b517019041 . _:b21217035 . _:b517018989 . _:b517019042 . _:b517018723 "4"^^ . _:b517019043 . _:b517018709 . _:b517018722 "4"^^ . _:b517019043 . . _:b517018733 "4"^^ . _:b517018732 "4"^^ . . . _:b517018925 . _:b517018735 "4"^^ . _:b517018956 . _:b21217030 "This meta-analysis included one additional randomised trial>>26<< that was not identified in the original PubMed search, and therefore included three randomised trials and one retrospective comparative study,20 with a total of 229 patients." . _:b517018957 . _:b517018958 . _:b21217036 "Non-randomised trials that have used this approach have reported survival outcomes of 14\u201319 months in this select group of patients,9, >>13<<, 14, 15, 16, 17, 20 and the results of one non-randomised study suggest that in patients with responding disease, this approach of switching to chemoradiotherapy could have better outcome than continuation of chemotherapy alone (overall" . _:b517018797 . _:b517018734 "4"^^ . _:b517018959 . _:b517018952 . _:b517018953 . _:b517018954 . _:b517018884 . _:b517018729 "4"^^ . . _:b517018955 . _:b517018948 . _:b517018949 . _:b21217042 . _:b517018950 . _:b517018728 "4"^^ . _:b517018951 . _:b517018944 . _:b517018945 . _:b517018946 . _:b517018731 "4"^^ . _:b517018947 . _:b517018972 . _:b517018973 . _:b517018974 . _:b517018730 "4"^^ . _:b517018975 . _:b517018968 . _:b517018969 . _:b517018741 "3"^^ . _:b517018970 . _:b517018971 . _:b517018964 . _:b517018965 . _:b517018740 "3"^^ . _:b517018966 . _:b517018967 . _:b517018960 . _:b517018961 . _:b517018743 "3"^^ . _:b517018962 . _:b517018699 . _:b517018963 . _:b517018915 . _:b517018725 . _:b517018988 . _:b517018989 . _:b517018742 "3"^^ . _:b517018990 . . _:b517018991 . _:b517018984 . _:b517018985 . _:b517018669 . _:b517018986 . _:b517018737 "4"^^ . . _:b517018987 . _:b517018980 . _:b517018981 . _:b517018995 . _:b517018982 . . _:b517018736 "4"^^ . _:b517018983 . _:b517019008 . _:b517018976 . _:b517018977 . _:b517018739 "3"^^ . _:b517018978 . _:b517018979 . _:b517019004 . _:b517019005 . _:b517019006 . _:b517019038 . _:b517018738 "4"^^ . _:b517019007 . _:b517019000 . _:b517019001 . _:b517018749 "3"^^ . _:b517019002 . _:b517019003 . _:b517018996 . _:b517018997 . _:b517018999 . _:b517018748 "3"^^ . _:b517018998 . _:b517018999 . _:b517018992 . . . _:b517018751 "3"^^ . _:b517018993 . _:b517018994 . _:b517018944 . . _:b517018995 . _:b517018892 . _:b517018893 . . _:b517018808 . _:b517018750 "3"^^ . _:b517018894 . _:b517018895 . _:b517019013 . _:b517018888 . _:b517018889 . _:b517018745 "3"^^ . _:b517018890 . _:b517018891 . _:b517018884 . _:b21217000 . _:b517018885 . . _:b517018744 "3"^^ . _:b517018886 . _:b517018887 . _:b517018880 . _:b517018881 . _:b517018747 "3"^^ . _:b517018774 . _:b517018882 . _:b517018883 . . _:b517018908 . _:b517018909 . _:b517018746 "3"^^ . _:b517018910 . _:b517018911 . _:b517018904 . _:b517018905 . _:b21216998 "in the UK and 7901 people died of the disease.1 At diagnosis, 30% of patients have locally advanced, inoperable disease.2 For these patients, chemotherapy alone or chemoradiotherapy are regarded as acceptable treatment options.3, 4, >>5<<, 6 Randomised trials7, 8 that compared the two strategies have had conflicting results and therefore have not been able to define a preferred standard of care." . _:b517018826 . _:b517018757 "3"^^ . _:b517018906 . _:b517018907 . _:b517018900 . . _:b517018933 . _:b517018756 "3"^^ . _:b517018901 . _:b517018902 . _:b517018903 . _:b517018896 . . _:b517018897 . _:b517018759 . _:b517018759 "3"^^ . _:b517018898 . _:b517018899 . _:b517018924 . _:b517018925 . _:b21217014 "3, 18 Three randomised, controlled trials>>19<<, 20, 21 with small numbers of patients have compared fluorouracil with gemcitabine chemoradiotherapy as primary treatment for locally advanced pancreatic cancer; one19 showed a significant overall survival benefit for gemcitabine-based" . _:b517018758 "3"^^ . _:b517018926 . . _:b517018927 . _:b517018823 . _:b517018920 . . _:b517018921 . _:b517018753 "3"^^ . _:b517018922 . . _:b517018923 . _:b517018916 . _:b517018917 . _:b21217002 . _:b517018752 "3"^^ . _:b517018918 . _:b517018807 . _:b517018919 . _:b517018912 . _:b517018913 . . _:b517018755 "3"^^ . _:b517018914 . _:b517018915 . _:b517018940 . _:b517018956 . _:b517018941 . _:b21217039 "Non-randomised trials that have used this approach have reported survival outcomes of 14\u201319 months in this select group of patients,9, 13, 14, 15, >>16<<, 17, 20 and the results of one non-randomised study suggest that in patients with responding disease, this approach of switching to chemoradiotherapy could have better outcome than continuation of chemotherapy alone (overall survival of" . _:b517018754 "3"^^ . _:b517018942 . _:b517018899 . _:b517018943 . _:b517018936 . _:b517018937 . _:b517018765 "3"^^ . _:b517018938 . _:b517018939 . _:b517018932 . _:b517018939 . _:b517018933 . _:b517018764 "3"^^ . _:b517018934 . _:b517018935 . _:b517018928 . _:b517018929 . _:b517018767 "3"^^ . _:b517018930 . _:b517018931 . _:b517018828 . _:b517018829 . _:b517018766 "3"^^ . _:b517018830 . _:b517018831 . . _:b517018824 . _:b517018825 . _:b21217005 . _:b517018761 "3"^^ . _:b517018826 . _:b517018827 . _:b517018820 . _:b517018739 . _:b517018821 . _:b517018760 "3"^^ . _:b517018822 . _:b517018823 . _:b517018816 . _:b517018966 . _:b517018868 . _:b517018817 . _:b517018763 "3"^^ . _:b517018818 . _:b517018819 . _:b517018844 . _:b517018845 . _:b517018762 "3"^^ . . _:b517018846 . _:b517018847 . _:b517018840 . _:b517018841 . _:b517018773 "3"^^ . _:b517018842 . _:b517019022 . _:b517018843 . _:b517018750 . _:b517018836 . _:b517018943 . _:b517018837 . _:b517018772 "3"^^ . _:b517018838 . _:b517018839 . _:b517018832 . _:b517018833 . _:b517018756 . _:b517018775 "3"^^ . _:b517018834 . _:b517018835 . . _:b517018860 . _:b517018861 . _:b517018774 "3"^^ . _:b517018736 . _:b517018862 . _:b517018863 . _:b517018856 . _:b517018857 . _:b517019018 . _:b517018769 "3"^^ . _:b517018858 . . _:b517018859 . _:b517018852 . . _:b517018768 "3"^^ . _:b517018853 . _:b517018854 . _:b517018855 . _:b517018848 . _:b517018849 . _:b517018771 "3"^^ . _:b517018850 . . _:b517018851 . _:b517018876 . _:b21217034 . _:b517018877 . _:b517018770 "3"^^ . _:b517018878 . _:b517018879 . _:b517018872 . _:b517018965 . _:b517018873 . _:b517018781 "3"^^ . _:b517018874 . _:b517018875 . _:b517018868 . . . _:b517018869 . _:b517018780 "3"^^ . _:b517018870 . _:b517018871 . _:b517018864 . _:b517018676 . _:b517018930 . _:b517018783 "3"^^ . _:b517018865 . _:b517018866 . _:b517018867 . . _:b517018710 . _:b517018764 . _:b517018765 . _:b517018782 "3"^^ . . . _:b517018766 . _:b517018767 . _:b517018705 . _:b517018760 . _:b517018761 . _:b517018777 "3"^^ . _:b517018762 . . _:b517018763 . _:b517018756 . _:b517018757 . _:b517018776 "3"^^ . _:b517018758 . _:b517018759 . _:b517018752 . _:b517018932 . _:b517018753 . _:b517018779 "3"^^ . _:b517018754 . _:b517018755 . _:b517018780 . _:b517018781 . _:b21217004 "Investigators of several studies have proposed the use of induction chemotherapy to select appropriate patients who are most likely to benefit from chemoradiation treatment.9, 10, >>11<< This approach spares intensive local treatment for patients with chemotherapy-resistant or rapidly progressing systemic disease." . _:b517018778 "3"^^ . _:b517018782 . _:b517018778 . . _:b517018783 . _:b517018776 . _:b517018896 . _:b517018777 . _:b517018789 "3"^^ . _:b517018778 . _:b517018779 . _:b517018772 . _:b517018773 . _:b517018788 "3"^^ . _:b517018774 . _:b517018775 . _:b517018768 . _:b517018769 . _:b517018791 "3"^^ . _:b517018770 . . _:b517018771 . _:b517018796 . _:b517018797 . _:b517018790 "3"^^ . . _:b517018798 . _:b517018799 . _:b21217010 "9, 12, 13, 14, 15, >>16<<, 17 The international, randomised, phase 3 study LAP-07 (NCT00634725), which is comparing chemoradiotherapy with chemotherapy, is expected to be reported in 2013." . _:b517018792 . _:b517018779 . _:b517018793 . _:b517018785 "3"^^ . _:b517018794 . _:b517018795 . _:b517018788 . _:b517018753 . _:b517018789 . _:b517018784 "3"^^ . . _:b517018790 . _:b517018791 . _:b517018784 . _:b517018785 . _:b21217034 "5, 23 Chemoradiotherapy for inoperable adenocarcinoma of the pancreas has been a standard treatment in the USA since a series of seminal studies from the Gastrointestinal Studies Group in 1981.>>6<< The relative benefit attributed to chemoradiotherapy compared with radiotherapy alone could be due in part to the extended administration of maintenance chemotherapy after chemoradiation in combined modality trial groups, which suggests" . _:b517018787 "3"^^ . _:b517018786 . _:b517018787 . _:b517018812 . _:b517018813 . . _:b517018786 "3"^^ . _:b517018814 . _:b517018815 . . _:b517018808 . _:b517018809 . _:b517018797 "3"^^ . _:b517018810 . _:b517018811 . _:b517018804 . _:b517018805 . _:b517018796 "3"^^ . _:b517018806 . _:b517018807 . _:b517018800 . . _:b517018801 . _:b517018799 "3"^^ . _:b517018802 . _:b517018803 . _:b517018700 . _:b517018701 . _:b517018798 "3"^^ . _:b517018702 . . . _:b517018994 . _:b517018703 . _:b517018696 . _:b517018697 . _:b517018793 "3"^^ . _:b517018698 . _:b517018699 . _:b517018692 . _:b517018693 . _:b517018792 "3"^^ . _:b517018694 . _:b517018695 . _:b517018865 . _:b517018850 . . _:b517018688 . _:b517018689 . _:b517018795 "3"^^ . . _:b517018690 . _:b517018691 . _:b517018716 . _:b517018841 . . _:b517018997 . _:b517018794 "3"^^ . _:b517018717 . _:b517018718 . _:b517018719 . . _:b517018712 . _:b517018713 . _:b517018805 "3"^^ . _:b517018714 . _:b517018715 . _:b517018708 . _:b517018958 . . _:b517018709 . _:b517018804 "3"^^ . _:b517018710 . _:b517018711 . _:b517018704 . _:b517018705 . _:b517018807 "3"^^ . _:b517018706 . _:b517018707 . _:b517018732 . _:b21217019 "patients have compared fluorouracil with gemcitabine chemoradiotherapy as primary treatment for locally advanced pancreatic cancer; one19 showed a significant overall survival benefit for gemcitabine-based treatment, but the others20, >>21<< did not show a significant difference between the regimens. A meta-analysis of these data again suggested a survival advantage of gemcitabine compared with fluorouracil chemoradiotherapy, but at the cost of greater toxicity." . _:b517018733 . _:b517018806 "3"^^ . _:b517018734 . . _:b517018735 . _:b517018728 . . _:b517018855 . _:b517018801 "3"^^ . _:b517018729 . _:b517018730 . . _:b517018731 . . _:b517018724 . _:b517018725 . _:b517018800 "3"^^ . _:b517018784 . _:b517018726 . _:b517018727 . _:b517018720 . _:b517018721 . . _:b517018803 "3"^^ . _:b517018722 . _:b517018723 . _:b517018748 . . _:b517018749 . _:b517018802 "3"^^ . _:b517018750 . _:b517018751 . _:b517018744 . _:b21216995 "In 2010, 8463 new cases of pancreatic cancer were diagnosed in the UK and 7901 people died of the disease.1 At diagnosis, 30% of patients have locally advanced, inoperable disease.>>2<< For these patients, chemotherapy alone or chemoradiotherapy are regarded as acceptable treatment options." . . _:b517018813 "2"^^ . _:b517018745 . . _:b517018746 . . _:b517018747 . _:b517018740 . _:b517018812 "2"^^ . _:b517018741 . _:b517018742 . _:b517018743 . _:b517018736 . _:b517018815 "2"^^ . _:b517018737 . _:b517018996 . _:b517018738 . . _:b517018739 . _:b517018814 "2"^^ . . _:b517018809 "2"^^ . . _:b517018808 "3"^^ . . _:b517018811 "2"^^ . . _:b517018810 "2"^^ . _:b21216998 . _:b517018821 "2"^^ . _:b517019012 . _:b517018820 "2"^^ . . _:b517018823 "2"^^ . _:b517018668 . _:b517018822 "2"^^ . . _:b517018669 . _:b517018670 . _:b517018671 . _:b517018664 . _:b21217002 "Investigators of several studies have proposed the use of induction chemotherapy to select appropriate patients who are most likely to benefit from chemoradiation treatment.>>9<<, 10, 11 This approach spares intensive local treatment for patients with chemotherapy-resistant or rapidly progressing systemic disease." . _:b517018817 "2"^^ . _:b517018665 . _:b517018706 . _:b517018666 . _:b517018667 . _:b517018660 . _:b517018816 "2"^^ . _:b517018661 . _:b517018788 . _:b517018662 . _:b517018663 . _:b517018819 "2"^^ . _:b517018657 . . _:b517018658 . . _:b517018659 . _:b517018684 . _:b21217053 . _:b517018818 "2"^^ . _:b517018685 . _:b517018661 . _:b517018686 . _:b517018687 . _:b517018680 . _:b517018829 "2"^^ . _:b517018681 . _:b517018660 . _:b517018682 . _:b517018683 . _:b517018676 . _:b517018962 . _:b517018828 "2"^^ . _:b517018677 . . _:b517018661 . _:b517018833 . _:b517018663 . _:b517018678 . _:b517018679 . _:b517018672 . _:b517018831 "2"^^ . . _:b517018673 . _:b517018662 . _:b517018674 . _:b517018675 . . _:b517018830 "2"^^ . _:b517018785 . _:b517018657 . _:b517018825 "2"^^ . _:b517018907 . _:b517018824 "2"^^ . _:b517018912 . _:b517018659 . _:b517018827 "2"^^ . _:b517019015 . _:b517018658 . . _:b517018922 . _:b517018826 "2"^^ . _:b517018669 . _:b517018837 "2"^^ . _:b517018668 . _:b517018836 "2"^^ . _:b517018671 . . _:b517018839 "2"^^ . _:b517018814 . . _:b517018670 . _:b517018838 "2"^^ . _:b517018665 . . _:b517018833 "2"^^ . _:b517018664 . . _:b517018832 "2"^^ . _:b517018667 . _:b517018835 "2"^^ . _:b517018666 . _:b517018726 . _:b517019003 . _:b517018834 "2"^^ . . _:b517018908 . _:b517018677 . . _:b517018845 "2"^^ . . _:b21217008 "9, 12, 13, >>14<<, 15, 16, 17 The international, randomised, phase 3 study LAP-07 (NCT00634725), which is comparing chemoradiotherapy with chemotherapy, is expected to be reported in 2013." . _:b517018676 . . _:b517018844 "2"^^ . _:b517018707 . _:b517018897 . _:b517018890 . _:b517018679 . _:b517019024 . _:b517018847 "2"^^ . . _:b517018678 . _:b517018846 "2"^^ . _:b517018673 . _:b517018902 . _:b517018841 "2"^^ . . _:b517018672 . _:b21217040 . _:b517018882 . _:b517018769 . _:b517018840 "2"^^ . _:b517018675 . _:b517018843 "2"^^ . _:b517018674 . _:b517018776 . _:b517018842 "2"^^ . _:b517018685 . _:b517018892 . _:b517018853 "2"^^ . _:b21217006 . _:b517018684 . _:b517018853 . . _:b517018852 "2"^^ . _:b517018687 . . _:b517018855 "2"^^ . . _:b517018686 . _:b517018854 "2"^^ . . _:b517018863 . _:b517018681 . _:b517018849 "2"^^ . _:b517018680 . . _:b21216997 . . _:b517018848 "2"^^ . _:b517018683 . _:b517018851 "2"^^ . _:b517018667 . _:b517018682 . _:b517018850 "2"^^ . _:b517018849 . _:b517018693 . _:b517018861 "2"^^ . _:b21217052 . _:b517018692 . _:b517018969 . _:b517018860 "2"^^ . _:b517018799 . _:b517018821 . _:b517018695 . _:b517018863 "2"^^ . _:b517018694 . . . . _:b517018862 "2"^^ . _:b517018689 . _:b21217019 . _:b517018857 "2"^^ . _:b517018790 . _:b517018688 . _:b21217016 . _:b517018754 . _:b517018856 "2"^^ . _:b517018691 . _:b517018859 "2"^^ . _:b21217038 . _:b517018690 . _:b517018858 "2"^^ . . . _:b517018701 . . _:b517018869 "2"^^ . . _:b517018700 . _:b517018868 "2"^^ . _:b517018714 . _:b517018703 . _:b517018871 "2"^^ . _:b517018702 . _:b517018870 "2"^^ . _:b517018689 . _:b517018697 . . _:b517018865 "2"^^ . _:b517018696 . _:b517018864 "2"^^ . _:b517018819 . _:b517018699 . _:b517018867 "2"^^ . . _:b517018698 . . _:b517018981 . _:b517018866 "2"^^ . _:b517018709 . _:b517018741 . _:b517018877 "2"^^ . _:b517018708 . _:b21217022 "Dose modifications for gemcitabine were made on the basis of neutrophil and platelet counts on the day of (or day before) administration, as previously described.>>23<< Capecitabine was withheld for grade 2 or higher non-haematological toxic effects until they resolved to grade 1; for recurrent grade 2 toxic effects, doses were sequentially reduced to 75% and then 50%." . _:b517018675 . _:b517018876 "2"^^ . _:b517018711 . _:b517018879 "2"^^ . . _:b517018710 . _:b517018878 "2"^^ . _:b517018836 . _:b517018705 . _:b517018873 "2"^^ . _:b517018704 . _:b517018872 "2"^^ . _:b517018707 . _:b517018875 "2"^^ . _:b517018706 . _:b517018874 "2"^^ . _:b517018735 . . _:b517018717 . _:b517018885 "2"^^ . _:b517018968 . _:b517018716 . _:b517018884 "2"^^ . _:b517019029 . _:b517018719 . . . _:b517018887 "2"^^ . _:b517018718 . _:b21217003 "Investigators of several studies have proposed the use of induction chemotherapy to select appropriate patients who are most likely to benefit from chemoradiation treatment.9, >>10<<, 11 This approach spares intensive local treatment for patients with chemotherapy-resistant or rapidly progressing systemic disease." . _:b517018886 "2"^^ . _:b517018713 . . _:b517018881 "2"^^ . . . _:b517018712 . _:b517018880 "2"^^ . _:b517018961 . . _:b517018715 . _:b21216997 "in the UK and 7901 people died of the disease.1 At diagnosis, 30% of patients have locally advanced, inoperable disease.2 For these patients, chemotherapy alone or chemoradiotherapy are regarded as acceptable treatment options.3, >>4<<, 5, 6 Randomised trials7, 8 that compared the two strategies have had conflicting results and therefore have not been able to define a preferred standard of care." . . _:b21217025 . _:b517018883 "2"^^ . _:b21217042 "non-randomised study suggest that in patients with responding disease, this approach of switching to chemoradiotherapy could have better outcome than continuation of chemotherapy alone (overall survival of 15\u00B70 vs 11\u00B77 months, p=0\u00B70009).>>9<< A prospective, phase 3 trial (LAP-07) to assess the additional benefit of chemoradiotherapy in this setting has completed accrual in Europe." . _:b517018734 . _:b517018714 . _:b517018882 "2"^^ . _:b517018725 . _:b517018893 "2"^^ . _:b517018724 . _:b517018892 "2"^^ . _:b517018727 . _:b517018895 "2"^^ . _:b517018726 . _:b517018783 . _:b21217031 . _:b517018963 . . _:b21217037 . _:b517018894 "2"^^ . _:b517018721 . . _:b21217047 "Of the previous studies that compared gemcitabine-based and fluorouracil-based chemoradiotherapy,19, 20, >>21<< at least one study19 and a meta-analysis22 suggested better survival outcomes with gemcitabine." . _:b517018889 "2"^^ . . . _:b517018720 . _:b517018888 "2"^^ . . _:b517018723 . _:b517018891 "2"^^ . _:b517018722 . _:b517018890 "2"^^ . _:b517018733 . _:b517018901 "2"^^ . _:b517018732 . . _:b517018900 "2"^^ . . _:b517018735 . . _:b517018903 "2"^^ . . _:b517018734 . _:b517018902 "2"^^ . . _:b517018870 . _:b517018729 . _:b517018897 "2"^^ . . _:b517018728 . . _:b517018896 "2"^^ . . _:b517018731 . . _:b517018724 . . . _:b517018899 "2"^^ . _:b517018678 . _:b517018730 . _:b517018845 . . _:b517018773 . _:b517018898 "2"^^ . _:b517018741 . . _:b517018662 . _:b517018909 "2"^^ . _:b21217029 "We also identified one meta-analysis>>22<< that compared gemcitabine-based with fluorouracil-based chemoradiotherapy." . _:b517018740 . _:b517018795 . _:b517018908 "2"^^ . _:b517018743 . _:b21217046 . _:b517018911 "2"^^ . _:b517018742 . _:b21217015 "3, 18 Three randomised, controlled trials19, >>20<<, 21 with small numbers of patients have compared fluorouracil with gemcitabine chemoradiotherapy as primary treatment for locally advanced pancreatic cancer; one19 showed a significant overall survival benefit for gemcitabine-based" . . _:b517018910 "2"^^ . _:b517018927 . _:b517018737 . . _:b517018905 "2"^^ . _:b517018736 . _:b517018904 "2"^^ . _:b517018976 . _:b517018739 . _:b517018907 "2"^^ . _:b517018738 . _:b517018657 . . _:b517018738 . . _:b517018906 "2"^^ . _:b517019028 . _:b517018749 . _:b517018744 . _:b517018917 "2"^^ . _:b517018748 . _:b517018701 . _:b21217041 . . . _:b517018916 "2"^^ . _:b517018751 . _:b517018767 . _:b517018848 . _:b517018919 "2"^^ . _:b517018750 . _:b21217007 "intensive local treatment for patients with chemotherapy-resistant or rapidly progressing systemic disease. Non-randomised studies that used this method of patient selection have reported overall survival of about 15\u201319 months.9, 12, >>13<<, 14, 15, 16, 17 The international, randomised, phase 3 study LAP-07 (NCT00634725), which is comparing chemoradiotherapy with chemotherapy, is expected to be reported in 2013." . _:b21217021 _:b21217024 . _:b517018918 "2"^^ . _:b517018745 . _:b517018913 "2"^^ . . . _:b517018744 . _:b517018812 . _:b517018912 "2"^^ . . _:b517018747 . . _:b517018915 "2"^^ . _:b517018746 . . _:b517018914 "2"^^ . _:b517018757 . _:b517018925 "2"^^ . _:b517018756 . _:b517018992 . _:b517018813 . _:b517018924 "2"^^ . _:b517018759 . . _:b517018680 . _:b517018927 "2"^^ . _:b517018758 . . . _:b517018926 "2"^^ . _:b517018753 . _:b517018731 . _:b517018921 "2"^^ . _:b21216999 . _:b517018752 . . _:b517018920 "2"^^ . _:b517018755 . _:b517019026 . _:b517018923 "2"^^ . _:b517018754 . _:b517018922 "2"^^ . . . _:b517018765 . _:b517018805 . _:b517018933 "2"^^ . . _:b517018764 . . _:b21217023 . _:b517018932 "2"^^ . _:b517018767 . _:b517018695 . _:b517018751 . _:b517018677 . _:b517018935 "2"^^ . _:b517018766 . _:b517018858 . _:b517018934 "2"^^ . _:b517018761 . . _:b517018929 "2"^^ . _:b517018760 . _:b517018928 "2"^^ . . _:b517018763 . _:b517019036 . _:b517018931 "2"^^ . . _:b517018972 . _:b517018762 . _:b517018930 "2"^^ . . . _:b517018773 . _:b517018941 "2"^^ . _:b517018772 . _:b517018924 . _:b517018940 "2"^^ . _:b517018775 . _:b517019004 . _:b517018815 . _:b517018943 "2"^^ . _:b517018774 . _:b517018942 "2"^^ . _:b517019049 . _:b517018769 . _:b517018869 . _:b517018937 "2"^^ . _:b517018768 . . _:b517018936 "2"^^ . . . . _:b517018771 . _:b517018939 "2"^^ . _:b517018770 . _:b517018938 "2"^^ . _:b21217001 . _:b517018781 . . _:b517019052 . _:b517018949 "2"^^ . _:b517018780 . . _:b517018948 "2"^^ . _:b517018783 . _:b517018951 "2"^^ . _:b517018782 . _:b517018970 . _:b517018950 "2"^^ . . _:b517018777 . . _:b517018945 "2"^^ . _:b517018690 . _:b517018942 . _:b517018776 . _:b517018944 "2"^^ . . _:b21217045 "Of the previous studies that compared gemcitabine-based and fluorouracil-based chemoradiotherapy,>>19<<, 20, 21 at least one study19 and a meta-analysis22 suggested better survival outcomes with gemcitabine." . _:b517018779 . _:b517018664 . . _:b517018775 . _:b517018947 "2"^^ . . _:b517018778 . _:b517018946 "2"^^ . _:b517018789 . _:b517018923 . . _:b517018957 "2"^^ . _:b517018825 . . _:b517018788 . _:b517018708 . _:b517018956 "2"^^ . _:b517019023 . _:b517018791 . _:b517018959 "2"^^ . _:b517018790 . _:b517018729 . _:b517018958 "2"^^ . _:b21217024 "Progression-free survival was chosen in preference to overall survival because, on the basis of the study by Huguet and colleagues,>>9<< we anticipated that activity could be detected earlier and with fewer patients." . _:b517018785 . _:b517018985 . _:b517018953 "2"^^ . _:b517018784 . _:b517018952 "2"^^ . _:b517018975 . . . _:b517018787 . _:b517018955 "2"^^ . _:b517018786 . _:b517018980 . _:b517018954 "2"^^ . . _:b517018797 . _:b517018965 "2"^^ . . _:b517018866 . _:b517018796 . . _:b517018730 . _:b517018964 "2"^^ . _:b517018799 . . _:b21217054 . . _:b517018967 "2"^^ . . _:b517018798 . _:b517018966 "2"^^ . . _:b517018793 . _:b517018961 "2"^^ . _:b517018792 . . _:b21217051 . _:b517018960 "2"^^ . . _:b517018795 . _:b21217041 "Non-randomised trials that have used this approach have reported survival outcomes of 14\u201319 months in this select group of patients,9, 13, 14, 15, 16, 17, >>20<< and the results of one non-randomised study suggest that in patients with responding disease, this approach of switching to chemoradiotherapy could have better outcome than continuation of chemotherapy alone (overall survival of 15\u00B70 vs" . _:b21217050 . _:b517018963 "2"^^ . _:b517018794 . _:b21216996 . _:b517018962 "2"^^ . _:b517018805 . _:b21216997 . _:b517018973 "2"^^ . _:b517018804 . _:b21216998 . _:b517018875 . _:b517018839 . . _:b517018972 "2"^^ . _:b517018807 . _:b21216999 . _:b517018975 "2"^^ . _:b517018806 . _:b517018974 "2"^^ . . _:b517018847 . _:b517018801 . . _:b517018969 "2"^^ . _:b517018733 . _:b517018800 . _:b21216994 . _:b517018968 "2"^^ . _:b517018803 . _:b21216995 . . _:b517018971 "2"^^ . . _:b21217004 . _:b517018802 . _:b517018970 "2"^^ . _:b517018813 . _:b21217005 . _:b517018787 . _:b517018906 . _:b517018981 "2"^^ . _:b21217020 "others20, 21 did not show a significant difference between the regimens. A meta-analysis of these data again suggested a survival advantage of gemcitabine compared with fluorouracil chemoradiotherapy, but at the cost of greater toxicity.>>22<< These data are, however, not conclusive enough to define practice, because the trials had small numbers of patients (19\u201362 per trial)." . _:b517018812 . _:b21217011 "9, 12, 13, 14, 15, 16, >>17<< The international, randomised, phase 3 study LAP-07 (NCT00634725), which is comparing chemoradiotherapy with chemotherapy, is expected to be reported in 2013." . _:b21217006 . . _:b517018980 "2"^^ . _:b21217010 . _:b517018815 . _:b21217007 . _:b517018983 "2"^^ . _:b517018814 . _:b21217000 . _:b517018982 "2"^^ . _:b517018809 . _:b21217001 . _:b517018977 "2"^^ . _:b517019046 . _:b517018808 . _:b21217002 . . _:b517018976 "2"^^ . _:b517018811 . _:b21217003 . _:b517018979 "2"^^ . _:b517018670 . _:b21217012 . _:b517018810 . _:b517018978 "2"^^ . _:b517018821 . _:b21217013 . _:b517018989 "2"^^ . _:b517018820 . _:b21217014 . . _:b517018988 "2"^^ . _:b517018823 . _:b21217015 . . . _:b517018771 . _:b517018991 "2"^^ . _:b517018822 . _:b21217008 . _:b517018990 "2"^^ . _:b517018718 . _:b517018817 . _:b21217009 . _:b517018985 "2"^^ . _:b517018700 . . _:b21217010 . _:b517018816 . . _:b517018984 "2"^^ . . _:b21217011 . . _:b517018819 . _:b517018904 . _:b517018987 "2"^^ . . _:b517018818 . _:b21217020 . _:b517018986 "2"^^ . _:b517018829 . _:b21217021 . _:b517018997 "2"^^ . _:b517018829 . _:b517018798 . _:b21217022 . _:b21217005 "spares intensive local treatment for patients with chemotherapy-resistant or rapidly progressing systemic disease. Non-randomised studies that used this method of patient selection have reported overall survival of about 15\u201319 months.>>9<<, 12, 13, 14, 15, 16, 17 The international, randomised, phase 3 study LAP-07 (NCT00634725), which is comparing chemoradiotherapy with chemotherapy, is expected to be reported in 2013." . _:b517018828 . . . _:b517018996 "2"^^ . _:b517019051 . . _:b21217023 . _:b517018831 . . _:b517018999 "2"^^ . _:b517018830 . _:b21217016 . _:b517018810 . _:b517018998 "2"^^ . . _:b21217017 . _:b517018825 . _:b517018743 . _:b517018993 "2"^^ . _:b517018682 . _:b517018824 . _:b21217018 . _:b517019053 . . _:b517018992 "2"^^ . . _:b517018659 . . _:b21217019 . _:b517018856 . _:b517018827 . _:b517018995 "2"^^ . . _:b517018826 . _:b21217021 . . _:b517018994 "2"^^ . _:b517018801 . _:b517018837 . _:b517019005 "2"^^ . . _:b517018836 . _:b517019004 "2"^^ . _:b517018839 . _:b517019007 "2"^^ . _:b21217055 "Additionally, in a retrospective series>>29<< of 85 patients that compared outcomes in patients who received adjuvant chemotherapy after primary gemcitabine-based chemoradiotherapy with those who did not, 2-year overall survival was significantly better in those who received the" . . _:b517018838 . _:b517019006 "2"^^ . _:b517018833 . _:b517019001 "2"^^ . . _:b517018832 . _:b517019000 "2"^^ . . _:b517018835 . _:b21216994 . _:b517019003 "2"^^ . _:b517018834 . _:b21217012 "Fluorouracil is most widely used, but gemcitabine radiosensitisation has been used in some studies because of its systemic activity in pancreatic cancer and potent radiosensitising properties.>>3<<, 18 Three randomised, controlled trials19, 20, 21 with small numbers of patients have compared fluorouracil with gemcitabine chemoradiotherapy as primary treatment for locally advanced pancreatic cancer; one19 showed a significant overall" . . _:b517019002 "2"^^ . _:b21216994 _:b21217004 . _:b21216994 _:b21217005 . _:b21216994 _:b21217006 . _:b517018845 . _:b21216994 _:b21217007 . _:b21216994 _:b21217000 . _:b517019013 "2"^^ . _:b21216994 _:b21217001 . _:b21216994 _:b21217002 . _:b517018844 . _:b21216994 _:b21217003 . _:b21216994 _:b21216996 . _:b517019012 "2"^^ . _:b21216994 _:b21216997 . _:b21216994 _:b21216998 . _:b517018847 . _:b21216994 _:b21216999 . _:b517019015 "2"^^ . _:b517018846 . _:b21216994 _:b21216995 . . _:b517019014 "2"^^ . _:b21216994 _:b21217020 . _:b517018757 . _:b517018841 . _:b21216994 _:b21217016 . _:b517019017 . _:b517019009 "2"^^ . . _:b21216994 _:b21217017 . . _:b517018840 . _:b21216994 _:b21217018 . _:b21216994 _:b21217019 . _:b517018766 . _:b21216994 _:b21217012 . _:b517019008 "2"^^ . . _:b21216994 _:b21217013 . _:b21216994 _:b21217014 . _:b517018843 . _:b21216994 _:b21217015 . _:b21216994 _:b21217008 . _:b517019011 "2"^^ . _:b21216994 _:b21217009 . _:b21216994 _:b21217010 . _:b21217038 "Non-randomised trials that have used this approach have reported survival outcomes of 14\u201319 months in this select group of patients,9, 13, 14, >>15<<, 16, 17, 20 and the results of one non-randomised study suggest that in patients with responding disease, this approach of switching to chemoradiotherapy could have better outcome than continuation of chemotherapy alone (overall survival" . _:b517018874 . _:b517018842 . _:b517018781 . _:b21216994 _:b21217011 . . _:b517019010 "2"^^ . _:b517018853 . . _:b517019021 "2"^^ . _:b517018804 . _:b517018852 . _:b517019007 . _:b517019020 "2"^^ . _:b517018855 . _:b517019023 "2"^^ . _:b517018854 . _:b517019022 "2"^^ . . _:b517018849 . . _:b517019017 "2"^^ . _:b517018848 . _:b517019016 "2"^^ . _:b517018851 . _:b517018816 . _:b517018715 . _:b517019019 "2"^^ . _:b517018850 . _:b517018789 . _:b517018842 . _:b517019018 "2"^^ . _:b517018861 . _:b517019029 "2"^^ . _:b517018860 . _:b517019028 "2"^^ . _:b517018863 . . _:b517019031 "2"^^ . _:b517018737 . _:b517018862 . _:b517019030 "2"^^ . _:b517018857 . _:b517019025 "2"^^ . _:b517018916 . . _:b517018988 . _:b517018856 . . . . _:b517019024 "2"^^ . . _:b517018859 . _:b517018818 . _:b517019027 "2"^^ . . _:b517018931 . _:b517018858 . . _:b517019026 "2"^^ . _:b517018869 . _:b517019037 "2"^^ . _:b517018868 . _:b517018742 . . _:b517019036 "2"^^ . _:b517018983 . _:b517018871 . _:b517018973 . _:b517019039 "2"^^ . _:b517018929 . . _:b517018870 . _:b21217021 _:b21217022 . _:b21217021 _:b21217023 . _:b517019038 "2"^^ . . _:b517018877 . . _:b517018865 . _:b517018671 . _:b517019033 "2"^^ . _:b517018938 . _:b517018864 . _:b517019032 "2"^^ . . _:b517018867 . _:b517019035 "2"^^ . _:b517018866 . _:b517018977 . . _:b517019034 "2"^^ . _:b517019037 . . _:b517018877 . _:b517018704 . _:b21217033 . _:b517018811 . _:b517019045 "2"^^ . _:b517018777 . _:b517018861 . _:b517018728 . _:b517018876 . . . _:b517019044 "2"^^ . . _:b517018835 . . _:b517018879 . . . _:b517019047 "2"^^ . . _:b517018878 . _:b517018828 . _:b517018834 . _:b517019046 "2"^^ . . _:b517018873 . _:b517019041 "2"^^ . _:b517018872 . . _:b517019027 . . _:b517019040 "2"^^ . _:b517018875 . _:b517018772 . _:b517019043 "2"^^ . _:b517018721 . _:b517018874 . _:b517018827 . _:b517019042 "2"^^ . _:b517018851 . . _:b517019053 "2"^^ . _:b517019052 "2"^^ . _:b517019047 . . _:b517018696 . _:b517019049 "2"^^ . . _:b517019048 "2"^^ . _:b517018685 . _:b517019051 "2"^^ . _:b517019050 "2"^^ . _:b21217008 . _:b517018894 . _:b517018979 . _:b517018960 . _:b517018957 . _:b21217032 "with locally advanced pancreatic cancer who are treated with chemotherapy alone, extracted from studies that combine patients with locally advanced pancreatic cancer and those with metastatic disease, ranges from 9\u00B79 to 10\u00B73 months.>>5<<, 23 Chemoradiotherapy for inoperable adenocarcinoma of the pancreas has been a standard treatment in the USA since a series of seminal studies from the Gastrointestinal Studies Group in 1981.6 The relative benefit attributed to" . . _:b21217003 . _:b517018987 . _:b517018910 . _:b517018758 . . _:b517018837 . . _:b517018824 . . _:b21217015 . . _:b21217006 "spares intensive local treatment for patients with chemotherapy-resistant or rapidly progressing systemic disease. Non-randomised studies that used this method of patient selection have reported overall survival of about 15\u201319 months.9, >>12<<, 13, 14, 15, 16, 17 The international, randomised, phase 3 study LAP-07 (NCT00634725), which is comparing chemoradiotherapy with chemotherapy, is expected to be reported in 2013." . _:b517018692 . . _:b21217013 "Fluorouracil is most widely used, but gemcitabine radiosensitisation has been used in some studies because of its systemic activity in pancreatic cancer and potent radiosensitising properties.3, >>18<< Three randomised, controlled trials19, 20, 21 with small numbers of patients have compared fluorouracil with gemcitabine chemoradiotherapy as primary treatment for locally advanced pancreatic cancer; one19 showed a significant overall" . . . _:b21217047 . _:b517018921 . . _:b517018940 . . _:b517018711 . . _:b517018732 . _:b517018803 . _:b21216999 "in the UK and 7901 people died of the disease.1 At diagnosis, 30% of patients have locally advanced, inoperable disease.2 For these patients, chemotherapy alone or chemoradiotherapy are regarded as acceptable treatment options.3, 4, 5, >>6<< Randomised trials7, 8 that compared the two strategies have had conflicting results and therefore have not been able to define a preferred standard of care." . . . . . _:b21217018 . _:b517018993 . _:b517018881 . _:b21217012 . _:b21217030 . . . _:b517018703 . . . . . _:b21217027 . . . . _:b517018951 . _:b517018822 . . _:b517018867 . . _:b517018846 . . _:b517018860 . _:b21216996 . _:b21217017 "3, 18 Three randomised, controlled trials19, 20, 21 with small numbers of patients have compared fluorouracil with gemcitabine chemoradiotherapy as primary treatment for locally advanced pancreatic cancer; one>>19<< showed a significant overall survival benefit for gemcitabine-based treatment, but the others20, 21 did not show a significant difference between the regimens." . _:b517018727 . . _:b517018681 . _:b517018780 . _:b21217028 . . _:b517018936 . _:b21217055 . _:b517018712 . _:b21217029 . . _:b21217030 . _:b21217018 "of patients have compared fluorouracil with gemcitabine chemoradiotherapy as primary treatment for locally advanced pancreatic cancer; one19 showed a significant overall survival benefit for gemcitabine-based treatment, but the others>>20<<, 21 did not show a significant difference between the regimens. A meta-analysis of these data again suggested a survival advantage of gemcitabine compared with fluorouracil chemoradiotherapy, but at the cost of greater toxicity." . _:b21217031 . _:b21217024 . . . _:b21217025 . _:b517018974 . . _:b21217026 . _:b21217027 . _:b517018883 . . _:b21217036 . _:b517018684 . _:b517018859 . _:b21217037 . . . _:b21217037 "Non-randomised trials that have used this approach have reported survival outcomes of 14\u201319 months in this select group of patients,9, 13, >>14<<, 15, 16, 17, 20 and the results of one non-randomised study suggest that in patients with responding disease, this approach of switching to chemoradiotherapy could have better outcome than continuation of chemotherapy alone (overall" . _:b21217038 . . _:b517019021 . _:b21217039 . _:b517018697 . _:b517019019 . _:b517018986 . _:b517018755 . _:b21217032 . . _:b517018895 . . . _:b21217033 . _:b517018893 . _:b21217034 . _:b21217035 . _:b517018745 . _:b517018765 . _:b21217040 "Non-randomised trials that have used this approach have reported survival outcomes of 14\u201319 months in this select group of patients,9, 13, 14, 15, 16, >>17<<, 20 and the results of one non-randomised study suggest that in patients with responding disease, this approach of switching to chemoradiotherapy could have better outcome than continuation of chemotherapy alone (overall survival of 15\u00B70" . _:b21217044 . _:b517018809 . _:b21217045 . . _:b517018688 . . _:b21217046 . _:b21217017 . _:b21217047 . _:b21216994 "introduction" . _:b21217040 . _:b21217041 . _:b21217042 . _:b21217043 . _:b517018982 . _:b517018978 . . _:b21217052 . _:b21217014 . . _:b21217053 . . _:b21217054 . . . _:b21217055 . _:b517018796 . _:b21217048 . _:b517018691 . . _:b21217049 . _:b517018919 . _:b517019040 . _:b21217050 . _:b517018786 . _:b21217051 . . _:b517018802 . _:b517018668 . _:b517018762 . _:b517018768 . _:b21217043 "However, the overall median survival of all registered patients was 12\u00B77 months (95% 11\u00B70\u201314\u00B75), which is better than previous outcomes in chemotherapy-only studies (roughly 10 months).>>4<<," . _:b517018891 . . . _:b517018955 . _:b517018832 . . _:b517019050 . _:b517018817 . . _:b517019000 . . . . . _:b517018876 . _:b517018660 . . _:b517018888 . _:b517018872 . _:b517019016 . _:b21217009 . _:b21217004 . "10.1016%2FS1470-2045%2813%2970021-4" . _:b21217039 . _:b517018885 . _:b517018950 . . _:b517018884 . _:b517018887 . _:b21217049 "Of the previous studies that compared gemcitabine-based and fluorouracil-based chemoradiotherapy,19, 20, 21 at least one study19 and a meta-analysis>>22<< suggested better survival outcomes with gemcitabine. However these studies used chemoradiotherapy without induction chemotherapy and were done in unselected patients." . _:b517018679 . _:b517018886 . _:b517018913 . . _:b517018881 . . _:b517018880 . . _:b517018883 . _:b21217020 . _:b517018864 . _:b517018882 . . _:b517018893 . _:b517018990 . _:b517018892 . . _:b517018862 . _:b517018895 . _:b517018894 . _:b517018889 . _:b517018698 . _:b517018888 . _:b517019045 . . _:b517018891 . . _:b517018926 . _:b517018890 . . _:b517019035 . _:b517018901 . _:b517018900 . . _:b517018903 . . . _:b517018902 . _:b517018873 . . _:b517018947 . _:b517018897 . _:b21217027 "We identified two randomised trials19, >>21<< that compared gemcitabine-based with fluorouracil-based chemoradiotherapy and one25 that compared gemcitabine-based with paclitaxel-based chemoradiotherapy." . _:b517018896 . _:b21217033 "with locally advanced pancreatic cancer who are treated with chemotherapy alone, extracted from studies that combine patients with locally advanced pancreatic cancer and those with metastatic disease, ranges from 9\u00B79 to 10\u00B73 months.5, >>23<< Chemoradiotherapy for inoperable adenocarcinoma of the pancreas has been a standard treatment in the USA since a series of seminal studies from the Gastrointestinal Studies Group in 1981.6 The relative benefit attributed to" . _:b517018899 . _:b21217028 . _:b21217007 . _:b517018889 . _:b517018746 . _:b517018898 . . _:b517018909 . _:b21217053 "group (11\u00B71 vs 9\u00B72 months, p=0\u00B7017), but at the expense of increased grade 4\u20135 toxic effects (41% vs 9%). Phase 1\u20132 studies that used full-dose gemcitabine in combination with radical doses of radiotherapy have also been reported.27, >>28<< Although outcomes from these studies are promising and the toxicities are acceptable, the trials were done in a small number of experienced centres, and the results might not be reproducible in a large multicentre setting." . . _:b517018800 . . _:b517018908 . _:b517018898 . _:b517018911 . _:b517018910 . _:b517018964 . _:b517018905 . _:b517018928 . _:b21217001 "3, 4, 5, 6 Randomised trials7, >>8<< that compared the two strategies have had conflicting results and therefore have not been able to define a preferred standard of care." . _:b517018904 . _:b517019005 . _:b517018702 . _:b517018907 . _:b21217035 "Non-randomised trials that have used this approach have reported survival outcomes of 14\u201319 months in this select group of patients,>>9<<, 13, 14, 15, 16, 17, 20 and the results of one non-randomised study suggest that in patients with responding disease, this approach of switching to chemoradiotherapy could have better outcome than continuation of chemotherapy alone" . _:b517018949 . _:b517018906 . _:b517018917 . _:b517019044 . _:b517018916 . . _:b517018948 . _:b517018919 . _:b517018909 . _:b517018918 . _:b517019025 . . . _:b517018913 . _:b517018912 . _:b517018954 . _:b21217023 "Quality-of-life questionnaires (EORTC QLQ-C>>3024<< and PAN26) were done at registration, week 17 (after induction chemotherapy), week 23 (immediately after chemoradiotherapy), and at weeks 26, 39, and 52." . _:b517018915 . . . _:b517018914 . _:b517018925 . . . _:b517019010 . _:b517018924 . _:b517018934 . _:b517019009 . _:b517018927 . . _:b517018926 . _:b517018998 . _:b517018921 . _:b517018747 . . _:b517018920 . _:b517018852 . _:b517018923 . _:b517018844 . _:b517018922 . . _:b517018946 . . _:b517018933 . _:b21217021 "methods" . _:b517018932 . _:b21217011 . . _:b517018935 . _:b517018770 . . _:b517018794 . _:b517018820 . _:b517018934 . _:b21217036 . _:b517018929 . . _:b517018928 . _:b517019030 . _:b517018931 . . _:b517018930 . _:b517018782 . _:b517019006 . . _:b517018941 . _:b517018719 . _:b517018940 . . . . _:b517019011 . _:b517018723 . _:b517018943 . . _:b517018942 . _:b517018683 . _:b517018937 . _:b517018793 . _:b517018905 . _:b517018936 . _:b517018857 . . _:b517018939 . _:b21216995 . _:b517018938 . . _:b517019001 . . . _:b517018945 . . _:b517018949 . . . _:b517018948 . _:b21217048 . . _:b517018843 . _:b21217026 "We identified two randomised trials>>19<<, 21 that compared gemcitabine-based with fluorouracil-based chemoradiotherapy and one25 that compared gemcitabine-based with paclitaxel-based chemoradiotherapy." . . _:b517018903 . . _:b517018951 . _:b517018885 . . _:b517018950 . _:b517018945 . _:b517018944 . _:b21217052 "group (11\u00B71 vs 9\u00B72 months, p=0\u00B7017), but at the expense of increased grade 4\u20135 toxic effects (41% vs 9%). Phase 1\u20132 studies that used full-dose gemcitabine in combination with radical doses of radiotherapy have also been reported.>>27<<, 28 Although outcomes from these studies are promising and the toxicities are acceptable, the trials were done in a small number of experienced centres, and the results might not be reproducible in a large multicentre setting." . _:b517018920 . _:b21217045 . _:b517018947 . _:b517018946 . . . _:b517018957 . _:b517018956 . . _:b517018959 . _:b517018763 . _:b517018958 . _:b517018716 . _:b517018953 . _:b517018952 . _:b21216996 "diagnosed in the UK and 7901 people died of the disease.1 At diagnosis, 30% of patients have locally advanced, inoperable disease.2 For these patients, chemotherapy alone or chemoradiotherapy are regarded as acceptable treatment options.>>3<<, 4, 5, 6 Randomised trials7, 8 that compared the two strategies have had conflicting results and therefore have not been able to define a preferred standard of care." . . _:b517018955 . _:b517018760 . . _:b517018791 . _:b517018954 . . _:b21217000 "3, 4, 5, 6 Randomised trials>>7<<, 8 that compared the two strategies have had conflicting results and therefore have not been able to define a preferred standard of care." . _:b517018965 . . _:b517018964 . _:b517018687 . _:b517018967 . . . _:b517018966 . _:b517018961 . . _:b517018960 . . _:b517018963 . . _:b517018962 . _:b517018973 . _:b517018972 . _:b517018975 . . . _:b517018974 . _:b21217026 . _:b517018969 . _:b517018959 . _:b517018968 . . . _:b517018971 . _:b517018971 . _:b517018970 . _:b517018991 . . _:b517018981 . . _:b517018980 . _:b517018914 . . _:b517018983 . _:b517018878 . _:b517018982 . _:b517019041 . .