胃癌课件英文最全.ppt

1、胃癌课件英文GASTRIC CANCERWorldwide incidence*Incidence per 100,000 population.Parkin DM,et al.CA Cancer J Clin.1999;49:33-64.China2nd most common cancer in the world,558400new cases and 405200 deaths.Almost 40%of cases occur in China.Pazdur R et al.Cancer management:A multidisciplinary approach.6th editi

2、on,2002 Countries in which the incidence of gastric carcinoma isextremely high include Japan,Costa Rica,Peru,Brazil,China,Korea,Chile,Taiwan,and the countries of the former Soviet Union.At diagnosis,approximately 50%of patients have gastric carcinoma that extends beyond the locoregional confines.App

3、roximately 50%of patients with locoregional gastric carcinoma cannot undergo a curativeresection(R0).In countries in the Western Hemisphere,gastriccarcinoma has migrated proximally,occurring most frequently along the proximal lesser curvature,in the cardia,and involving the gastroesophageal junction

4、.It is possible that in the coming decades these changing trends will also occur in South America and Asia.Nearly 70%to 80%of resected gastric carcinoma specimens have metastases in the regional lymph nodes.Thus,it is common to encounter patients with advanced gastric carcinoma at the outset.In the

5、Western Hemisphere,R0 resection is possible in approximately 50%to 80%of patients.The median survival of patients who undergo an R0 resection is approximately 25 months,and 5-year survival rates range from 30%to 37%.NCNN GuidelinesThe workup permits classification of patients into 1 of 2 groups:(1)p

6、atients with apparent locoregional carcinoma(stages I to III or M0),and(2)those with obvious metastatic carcinoma(stage IV or M1).Patients with apparent locoregional disease can be further classified:(1)those who are medically fit and whose cancer is resectable,(2)those who are medically fit but who

7、se cancer is unresectable,and(3)those who are inoperable(medically unfit).Global ConsensusGood local control is essential to cure gastric carcinomaThe only potentially curative treatment for localized gastric cancer is surgery.Most gastric cancers are diagnosed at an advanced stage.The 5-year surviv

8、al rate after“curative resection”for gastric cancer is only between 30%and 40%.The efficacy of chemotherapy with palliative intent is now widely accepted.Chemotherapy of Gastric CancerKohne CH,Wils JA,Wilke HJ:Developments in the treatment of gastric cancer in Europe.Oncology(Huntingt)14:22-25,2000

9、Chemotherapy of Gastric CancerFluorouracil(5-FU)is one of the most effective and widely used drugs in the treatment of advanced gastric cancer(AGC),producing a response rate of approximately 20%,with manageable toxicity.Overall survival of between 5 and 7 months has been reported for 5-FU monotherap

10、y in phase III randomized studies.Coombes R,Chilvers CE,Amadori D,et al:An International Collaborative Cancer Group(ICCG)study.Ann Oncol 5:33-36,1994 6.Chemotherapy of Gastric Cancer5-FU modulation by folinic acid(FA)has generally resulted in enhanced antitumor efficacy(22%to 48%overall response rat

11、e)and has led to some complete responses(5%to 9%).All current reference combination regimens in AGC contain 5-FU.Louvet C,De Gramont A,Demuynck B,et al:.Ann Oncol 2:229-230,1991 Chemotherapy of Gastric Cancer5-FU,doxorubicin,and mitomycin(FAM);5-FU,doxorubicin,and high-dose methotrexate(FAMTX);etopo

12、side,doxorubicin,and cisplatin(EAP);etoposide,leucovorin,and 5-FU(ELF);epirubicin,cisplatin,and 5-FU continuous infusion(ECF);cisplatin,epirubicin,leucovorin,and 5-FU(PELF);cisplatin and 5-FU.Chemotherapy of Gastric CancerSeveral randomized studies comparing FAM versus FAMTX(5-FU,adriamycin,and meth

13、otrexate with leucovorin rescue),FAMTX versus ECF(epirubicin,cisplatin,and 5-FU),and FAMTX versus ELF(etoposide,leucovorin,and 5-FU)versus 5-FU plus cisplatin have been reported in the past several years.No one standard therapy has emerged from these trials.Outside of clinical trials,the recommended

14、 chemotherapy for advanced gastric carcinoma is either cisplatin-based or 5-FU-based combination chemotherapy.Chemotherapy of Gastric CancerThe new agents include paclitaxel,docetaxel,irinotecan,UFT,oral etoposide,and S-1.Several reports of newer combination chemotherapy regimens have also appeared.

15、A number of newer oral agents also hold promise in the treatment of gastric carcinoma.Agents that have not been extensively studied include capecitabine,oxaliplatin.In addition,a number of new categories of agents are of interest.These include vaccines,antireceptor agents,and antiangiogenic agents.A

16、 number of chemotherapy combinations are currently in phase III trials,and we anticipate that a widely accepted front-line standard for patients with advanced gastric carcinoma might emerge in the near future.NCNN GuidelinesThe landmark trial is the Intergroup trial INT-0116.Eligibilityincluded pati

17、ents with T3 and or N+adenocarcinoma of the stomachor gastroesophageal junction.After a resection with negativemargins,603 patients were randomly assigned to either observationalone or postoperative combined modality therapy consisting of 5monthly cycles of bolus chemotherapy with 45 Gy concurrent w

18、ithcycles 2 and 3.There was a significant decrease in local failure asthe first site of failure(19%versus 29%)as well as an increase inmedian survival(36 versus 27 months),3-year relapse-free survival(48%versus 31%),and overall survival(50%versus 41%,=.005)with combined modality therapy.NCNN Guideli

19、nesA patient whose surgical pathologic stage is T1,N0,M0 may be observed and not treated with adjuvant therapy.All patients with an R0 resection who have T2,N0 along with adverse features(ie,poorly differentiated or higher grade cancer,lymphovascular invasion,neural invasion,or age younger than 50 y

20、ears)should receive adjuvant chemoradiotherapy;those patients without adverse features may be observed.NCNN GuidelinesPatients with R1 resections should be offered radiotherapy(45 to 50.4 Gy)with concurrent 5-FU-based radiosensitization plus 5-FU with or without leucovorin.NCNN GuidelinesAll patient

21、s with an R0 resection who have T3,T4 or any T,N+cancer should be offered adjuvant chemoradiotherapy(ie,radiotherapy 45 Gy with concurrent 5-FU/leucovorin).It should also be noted that 20%of patients in the Intergroup-0116 trial had cancers that involved the gastroesophageal junction;therefore,adjuv

22、ant chemoradiotherapy should also be recommended for patients with similar cancers (again,patients with T1,N0,M0 tumors may be observed as can patients with T2,N0 without adverse features).margins,603 patients were randomly assigned to either observationOver all response rate was 22.There were no tr

23、eatmwnt-related deaths.63 patients were evaluated for response.These include vaccines,antireceptor agents,and antiangiogenic agents.Best responses in the 49 assessable patients were two complete responses and 20 partial responses,giving an overall best response rate of 44.Neutropenic fever was not o

24、bserved.6%,respectivelyThe median patient age was 44 years(range,28 to 72 years);21 patients were male(46.558400new cases and 405200 deaths.72 patients received 267 courses of chemotherapy(4 courses).Baba;Kyushu University,Fukuoka,Japan;Hiroshima Red Cross Hospital,Hiroshima,JapanAs previously discu

25、ssed,it is recommended that patients with negative margins(R0 resection)and no evidence of metastatic carcinoma after gastrectomy may be considered for adjuvant chemoradiation based on the results of the Intergroup trial(INT-0116).2%and median survival time of 263 days.In view of the favorable respo

26、nse rate and toxicity profile,this protocol will be further assessed in a multicenter phase II trial.Corticosteroids were administered from day-1 to day 4,and GCSF recommended from day 3 to day 9.In addition,a number of new categories of agents are of interest.Phase II Study of Oxaliplatin,Fluoroura

27、cil,and Folinic Acid in Locally Advanced or Metastatic Gastric Cancer Patients.NCNN GuidelinesAs previously discussed,it is recommended that patients with negative margins(R0 resection)and no evidence of metastatic carcinoma after gastrectomy may be considered for adjuvant chemoradiation based on th

28、e results of the Intergroup trial(INT-0116).NCNN GuidelinesIn the absence of M1 carcinoma,patients with R2 resections may be offered(1)radiation therapy(45 to 50.4Gy)with concurrent 5-FU-based radiosensitization;(2)5-FU-based,cisplatin-or oxaliplatin-based,taxane-based,or irinotecan-based chemothera

29、py;(3)best supportive care,if performance status is poor;(4)enrollment in a clinical trial.Inoperable patientsshould undergo restaging after completion of chemoradiotherapy.If a complete response of the carcinoma is determined,these patients should be observed or have surgery if it is deemed appropr

30、iate.If there is evidence of residual or M1 disease,patients may be offered salvage therapyDocetaxel,cisplatin,UFT and leucovorin combination chemotherapy in advanced gastric cancer.Abstract No:4231S.C.Oh,Korea University,Seoul,Republic of KoreaMethods:Without considering previous treatment,Seventy-

31、two patients were enrolled in this study at Korea University Hospital from September 2001 to April 2003.Docetaxel 60 mg/m2 was given as intravenous infusion for 1 hour at day 1 and cisplatin 75 mg/m2 was intravenous infusion after docetaxel infusion at day 1.Oral UFT 360 mg/m2 and leucovorin 45 mg/d

32、ay were administered for 21 consecutive days followed by a 7-day drug free interval.This schedule was repeated every 4 weeks.Results72 patients received 267 courses of chemotherapy(4 courses).63 patients were evaluated for response.6 patients achieved CR(9.5%)and 25 patients PR(39.7%),ORR was observ

33、ed in 49.2%(95%confidence interval,36.9-61.5%).The major toxicity was neutropenia which reached grade 3-4 in 65.2%.However,most of the patients except three patients who died due to sepsis,recovered from neutropenia without complication with support of granulocyte or granulocyte-macrophage colony st

34、imulating factor.Non-hematologic toxicities were usually mild.Grad 3-4 nausea and vomiting were observed in 17.9%.The median time to progression was 27 weeks(range,1 to 88 weeks),Median response duration was 26 weeks(range,2 to 72 weeks).ConclusionsThese results suggests that the combination of doce

35、taxel,cisplatin,oral UFT and leucovorin is effective and tolerable regimen for the treatment of advanced gastric cancer with supported of a granulocyte or granulocyte-macrophage colony stimulating factor.Oxaliplatin-based regimen as neoadjuvant chemotherapy for Chinese patients with advanced gastric

36、 cancer:Preliminary results of a phase II study.Abstract No:4184J.-F.Ji;University School of Oncology,Beijing Cancer Hospital,Beijing,China;Beijing Cancer Hospital,Beijing,ChinaMethods:15 pts(Stage IIIb or IV)have been enrolled by now.All pts had histologically proven gastric adenocarcinoma and no p

37、revious palliative chemotherapy.Median age:59 years(33-69 years),male/female ratio:10/5,performance status:0-2.Pts received OXA 130 mg/m2 3H-infusion day 1,leucovorin(LV)200 mg/m2(2H-infusion)followed by 5FU 400mg/m2(bolus)and 5FU 2.5g/m(22h-continuous infusion)day 1,repeated every 3 weeks.Efficacy

38、was evaluated after 2 cycles.ResultsAll pts are evaluable for response with a more than 50%tumor reduction in 7 of 15(46.7%)pts,SD was observed in 6 pts(40.0%)and PD in 2(13.3%).14 of 15 pts received a total 6 cycles(pre-op+or-post-op)of chemotherapy and all 15 pts came to surgery after receiving 2-

39、6 cycles.OXA-5FU/LV was general well tolerated.The most common toxicity was Grade(Gr)2 or 3 neutropenia and diarrhea or Gr 2 nausea/vomiting,No patients experienced Gr 4 toxicity.Neutropenic fever was not observed.An R0 curative resection was possible in 7 pts.There were no postoperative mortalities

40、 and no treatment related deaths;14 of 15 pts are surviving(2 to 24 months)and one PD pt died of disease 2 months after surgery.Pathologic examinations of operative samples showed significant chemotherapy-induced changes in 6 pts.The trial is still open and more mature data will be available at the

41、meeting.Conclusions:In view of the favorable response rate and toxicity profile,this protocol will be further assessed in a multicenter phase II trial.Phase II study of weekly paclitaxel in patients with advanced gastric cancer in Japan.Abstract No:4226:H.Baba;Kyushu University,Fukuoka,Japan;Hiroshi

42、ma Red Cross Hospital,Hiroshima,JapanMethods:The eligibility criteria were as follows;1)histologically proven gastric cancer with measurable lesion,2)PS 0-2,3)age75,4)adequate bone marrow,liver,renal functions,5)life expectancy of more than 3 months.Fifty-nine patients were treated with weekly 1h-in

43、fusion paclitaxel of 80mg/m2 with a short premedication for consecutive 3 weeks with one week rest as one course.ResultsPatients characteristics were as follows:male/female;44/15,mean age of 64,PS 0/1/2;27/20/12,previous treatment(-)/(+);11/48.Median treatment cycle was 3.Over all response rate was

44、22.2%and median survival time of 263 days.There were no treatmwnt-related deaths.Hematologic and nonhematologic toxicities more than grade 3 included leucopenia(15.3%),neutopenia(20.3%),fatigue(1.7%),and arthralgia(1.7%).An improvement in PS,food intake,pain,and ascites accumulation was recognized i

45、n 17.3%,16.4%,23.1%,and 47.6%,respectively ConclusionsWeekly paclitaxel was active for both previously untreated and treated patients with advanced gastric cancer with a minimum toxicity profile,and can be useful to improve QOL and prolong survival time of patients.Docetaxel-cisplatin-5FU(TCF)versus

46、 docetaxel-cisplatin(TC)versus epirubicin-cisplatin-5FU(ECF)as systemic treatment for advanced gastric carcinoma(AGC):A randomized phase II trial of the Swiss Group for Clinical Cancer Research(SAKK).Abstract No:4020:A.D.Roth,Oncosurgery,Geneva University Hospital,Geneva,Switzerland;Methods:Patients

47、(pts)with AGC,without prior palliative chemotherapy,with bidimentionally measurable disease,PS 1,normal blood counts,hepatic and renal functions,were randomized to receive up to 8 cycles q3w of TC(docetaxel 85mg/m2,ciplatine 75mg/m2),TCF(like TC+5-FU continuous infusion(CI)300mg/m2/d for 2w)or ECF(e

48、pirubicin 50mg/m2,cisplatin 60mg/m2,5-FU CI 200mg/m2/d for 3w).Results:Among 121pts enrolled,119 were treated and included in the analysis.5 pts are still on treatment(3 ECF and 2 TCF).Preliminary results are summarized below.A total of 554 treatment cycles are documented up to now.A median of 5,4.5

49、 and 4 cycles of ECF,TC and TCF were given,respectively.Hematotoxicity was the main toxicity in all 3 arms with grade 3 granulopenia in 73%,76%and 58%of the pts for TC,TCF and ECF,respectively.Febrile neutropenia(FN)occurence in 10 of the first 21 pts enrolled in docetaxel based regimens led to decr

50、ease docetaxel from 85 to 75mg/m2 in TC and TCF,resulting in lesser FN occurence.Grade 3 non-hematologic toxicity was infrequent(=12 weeks;adequate hepatic,renal,and bone marrow function.not received chemotherapy or radiotherapy in recent 4 weeks;signed informed consent was obtained from all patient