5、消化系统肿瘤消化系统肿瘤 (6).pdf
《5、消化系统肿瘤消化系统肿瘤 (6).pdf》由会员分享,可在线阅读,更多相关《5、消化系统肿瘤消化系统肿瘤 (6).pdf(9页珍藏版)》请在得力文库 - 分享文档赚钱的网站上搜索。
1、The new england journal of medicinen engl j med 362;14 nejm.org april 8,20101273original articleCisplatin plus Gemcitabine versus Gemcitabine for Biliary Tract CancerJuan Valle,M.D.,Harpreet Wasan,M.D.,Daniel H.Palmer,M.D.,Ph.D.,David Cunningham,M.D.,Alan Anthoney,M.D.,Anthony Maraveyas,M.D.,Ph.D.,S
2、rinivasan Madhusudan,M.D.,Ph.D.,Tim Iveson,M.D.,Sharon Hughes,B.Sc.,Stephen P.Pereira,M.D.,Ph.D.,Michael Roughton,M.Sc.,and John Bridgewater,M.D.,Ph.D.,for the ABC-02 Trial Investigators*From Christie Hospital,Manchester(J.V.);Hammersmith Hospital,Imperial College Health Care Trust(H.W.),Royal Marsd
3、en Hospital(D.C.),Cancer Research United Kingdom and University College London Cancer Trials Centre(S.H.,M.R.),Institute of Hepatology,University College London(S.P.P.),and University College London Can-cer Institute(J.B.)all in London;Univer-sity Hospital Birmingham,Birmingham(D.H.P.);St.Jamess Hos
4、pital,Leeds(A.A.);Castle Hill Hospital,Hull(A.M.);Notting-ham University Hospitals,Nottingham(S.M.);and Southampton University Hos-pitals,Southampton(T.I.)all in the United Kingdom.Address reprint requests to Dr.Bridgewater at the University Col-lege London Cancer Institute,72 Huntley St.,London WC1
5、E 6AA,United Kingdom,or at j.bridgewaterucl.ac.uk.*The investigators in the Advanced Bil-iary Cancer(ABC)-02 Trial are listed in the Appendix.Drs.Valle,Wasan,and Bridgewater contributed equally to this article.This article(10.1056/NEJMoa0908721)was updated on July 7,2010,at NEJM.org.N Engl J Med 201
6、0;362:1273-81.Copyright 2010 Massachusetts Medical Society.AbstractBackgroundThere is no established standard chemotherapy for patients with locally advanced or metastatic biliary tract cancer.We initially conducted a randomized,phase 2 study involving 86 patients to compare cisplatin plus gemcitabi
7、ne with gemcitabine alone.After we found an improvement in progression-free survival,the trial was extended to the phase 3 trial reported here.MethodsWe randomly assigned 410 patients with locally advanced or metastatic cholangio-carcinoma,gallbladder cancer,or ampullary cancer to receive either cis
8、platin(25 mg per square meter of body-surface area)followed by gemcitabine(1000 mg per square meter),each administered on days 1 and 8,every 3 weeks for eight cycles,or gemcit-abine alone(1000 mg per square meter on days 1,8,and 15,every 4 weeks for six cycles)for up to 24 weeks.The primary end poin
9、t was overall survival.ResultsAfter a median follow-up of 8.2 months and 327 deaths,the median overall survival was 11.7 months among the 204 patients in the cisplatingemcitabine group and 8.1 months among the 206 patients in the gemcitabine group(hazard ratio,0.64;95%confidence interval,0.52 to 0.8
10、0;P0.001).The median progression-free sur-vival was 8.0 months in the cisplatingemcitabine group and 5.0 months in the gemcitabine-only group(P0.001).In addition,the rate of tumor control among pa-tients in the cisplatingemcitabine group was significantly increased(81.4%vs.71.8%,P=0.049).Adverse eve
11、nts were similar in the two groups,with the exception of more neutropenia in the cisplatingemcitabine group;the number of neutrope-nia-associated infections was similar in the two groups.ConclusionsAs compared with gemcitabine alone,cisplatin plus gemcitabine was associated with a significant surviv
12、al advantage without the addition of substantial toxicity.Cisplatin plus gemcitabine is an appropriate option for the treatment of patients with advanced biliary cancer.(ClinicalTrials.gov number,NCT00262769.)The new england journal of medicinen engl j med 362;14 nejm.org april 8,20101274Biliary tra
13、ct cancer is an uncom-mon cancer in developed countries.There are approximately 1200 new cases in the United Kingdom1 and 9000 new cases in the Unit-ed States per year,although the incidence is in-creasing,perhaps related to gallstone disease.2 Most patients have advanced disease at presenta-tion an
14、d relapse despite surgery.3 Although ad-vanced biliary tract cancer can have a response to chemotherapy,there is no recognized standard palliative regimen because no single randomized study has ever been sufficiently robust to define a schedule;fluoropyrimidines,4,5 cisplatin,6 and gemcitabine7,8 ha
15、ve shown activity.Gemcitabine(Gemzar,Eli Lilly)treatment for biliary tract cancer has been increasingly pre-scribed by oncologists who specialize in hepato-biliary disease because of its use in pancreatic cancer.Cisplatin is known to have an additive or synergistic effect in combination with gemcita
16、bine in a number of different tumor types(e.g.,lung,9 bladder,10 and head and neck11 cancers).We pre-viously found an improvement in 6-month pro-gression-free survival from 47.7%to 57.1%in a randomized,phase 2 trial(the Advanced Biliary Cancer ABC-01 trial)comparing cisplatin plus gemcitabine with g
17、emcitabine alone;that trial in-volved 86 patients.12 That study was extended to become a phase 3 trial(the ABC-02 trial)with a planned recruitment total of 400 patients and a primary end point of overall survival.Methodsstudy DesignThis randomized,controlled,phase 3 trial was de-signed and developed
18、 by the ABC-02 Trial Man-agement Group under the auspices of the Upper Gastrointestinal Cancer Clinical Studies Group of the United Kingdom National Cancer Research Institute.The study was conducted by investiga-tors at 37 centers in the United Kingdom,and data were collected and analyzed at the Can
19、cer Research United Kingdom and University College London Cancer Trials Centre,London.The trial was initially designed as a randomized,phase 2 study involving 86 patients(the ABC-01 trial),conducted between February 2002 and June 2004.The trial was extended into a phase 3 trial(the ABC-02 trial)beca
20、use of an apparent benefit in progression-free survival;this extension used a similar approach to that described previously.13 The same treatment regimens and eligibility cri-teria were used in both phases.Investigators were unaware of the overall survival analysis in the ABC-01 trial,as mandated by
21、 the independent data and safety monitoring committee.This trial was approved by a research ethics committee,and all necessary regulatory approv-als were obtained.All patients were required to give written informed consent before random assignment,and the trial was conducted in ac-cordance with the
22、Declaration of Helsinki.An independent data and safety monitoring board regularly reviewed the data on safety.Lilly Oncology provided the investigators with gemcitabine at no cost but was not involved in the accrual or analysis of the data,the interpre-tation of the results,or the preparation of the
23、 manuscript.PatientsPatients were eligible for the study if they were 18 years of age or older and had received a histopatho-logical or cytologic diagnosis of nonresectable,recurrent,or metastatic biliary tract carcinoma(intrahepatic or extrahepatic cholangiocarcinoma,gallbladder cancer,or ampullary
24、 carcinoma);an Eastern Cooperative Oncology Group(ECOG)per-formance status of 0,1,or 2(on a scale ranging from 0 to 5,with lower scores indicating a high-er level of functioning);and an estimated life ex-pectancy of more than 3 months.Other eligibility criteria were adequate hematologic and biochem-
25、ical function,in particular a total bilirubin level of 1.5 times the upper limit of the normal range or less,liver-enzyme levels that were five times the upper limit of the normal range or less,renal func-tion with levels of serum urea and serum creati-nine that were less than 1.5 times the upper li
- 配套讲稿:
如PPT文件的首页显示word图标,表示该PPT已包含配套word讲稿。双击word图标可打开word文档。
- 特殊限制:
部分文档作品中含有的国旗、国徽等图片,仅作为作品整体效果示例展示,禁止商用。设计者仅对作品中独创性部分享有著作权。
- 关 键 词:
- 5、消化系统肿瘤消化系统肿瘤 6 消化系统 肿瘤
限制150内