胃癌英文Gastric-Cancer课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,二级,三级,四级,五级,*,Chemotherapy in Gastric Cancer,Chemotherapy in Gastric Canc,1,GASTRIC CANCER,Worldwide incidence*,*,Incidence per 100,000 population.,Parkin DM, et al.,CA Cancer J Clin.,1999;49:33-64.,Male16.4,Female8.2,Male36.3,Female16.9,Male77.9,Female33.3,Male10.8,Female4.9,Male43.6,Female19.0,Male5.9,Female2.6,Male11.5,Female 4.3,Male18.6,Female13.3,Male8.4,Female4.0,Eastern,Europe,Japan,Australia/,New Zealand,China,Northern,Africa,Southern,Africa,Central,America,Western,Europe,North,America,2nd 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 edition,2002,GASTRIC CANCERWorldwide incid,2,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. Approximately 50% of patients with locoregional gastric carcinoma cannot undergo a curativeresection (R0).,Countries in which the inciden,3,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.,It is possible that in the coming decades these changing trends will also occur in South America and Asia.,In countries in the Western He,4,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 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%.,Nearly 70% to 80% of resected,5,NCNN Guidelines,The workup permits classification of patients into 1 of 2 groups: (1)patients 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 whose cancer is unresectable, and (3) those who are inoperable (medically unfit).,NCNN GuidelinesThe workup perm,6,Global Consensus,Good local control is essential to cure gastric carcinoma,The only potentially curative treatment for localized gastric cancer is surgery.,Global ConsensusGood local con,7,Most gastric cancers are diagnosed at an advanced stage.,The 5-year survival 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 Cancer,Kohne CH, Wils JA, Wilke HJ: Developments in the treatment of,gastric cancer in Europe.Oncology (Huntingt) 14: 22-25, 2000,Most gastric cancers are diagn,8,Chemotherapy of Gastric Cancer,Fluorouracil (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 monotherapy 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 Cancer,9,Chemotherapy of Gastric Cancer,5-FU modulation by folinic acid (FA) has generally resulted in enhanced antitumor efficacy (22% to 48% overall response rate) 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 Cancer,10,Chemotherapy of Gastric Cancer,5-FU, doxorubicin, and mitomycin (FAM);,5-FU, doxorubicin, and high-dose methotrexate (FAMTX);,etoposide, 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 Cancer,11,Chemotherapy of Gastric Cancer,Several randomized studies comparing FAM versus FAMTX (5- FU, adriamycin, and methotrexate 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 chemotherapy for advanced gastric carcinoma is either cisplatin- based or 5- FU- based combination chemotherapy.,Chemotherapy of Gastric Cancer,12,Chemotherapy of Gastric Cancer,The new agents include paclitaxel,docetaxel, irinotecan, UFT ,oral etoposide, and S- 1.,Several reports of newer combination chemotherapy regimens have also appeared. 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 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.,Chemotherapy of Gastric Cancer,13,NCNN Guidelines,The landmark trial is the Intergroup trial INT- 0116. Eligibility,included patients with T3 and or N+ adenocarcinoma of the stomach,or gastroesophageal junction. After a resection with negative,margins, 603 patients were randomly assigned to either observation,alone or postoperative combined modality therapy consisting of 5,monthly cycles of bolus chemotherapy with 45 Gy concurrent with,cycles 2 and 3. There was a significant decrease in local failure as,the first site of failure (19% versus 29%) as well as an increase in,median 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 GuidelinesThe landmark tr,14,NCNN Guidelines,A 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 years) should receive adjuvant chemoradiotherapy; those patients without adverse features may be observed.,NCNN GuidelinesA patient whose,15,NCNN Guidelines,Patients 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 GuidelinesPatients with R,16,NCNN Guidelines,All patients 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, adjuvant 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).,NCNN GuidelinesAll patients wi,17,NCNN Guidelines,As 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 the results of the Intergroup trial (INT-0116).,NCNN GuidelinesAs previously d,18,NCNN Guidelines,In 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 chemotherapy;,(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 appropriate. If there is evidence of residual or M1 disease, patients may be offered salvage therapy,NCNN GuidelinesIn the absence,19,Docetaxel, cisplatin, UFT and leucovorin combination chemotherapy in advanced gastric cancer.,AbstractNo:4231,S. C. Oh, Korea University, Seoul, Republic of Korea,Methods:,Without considering previous treatment, Seventy-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/day were administered for 21 consecutive days followed by a 7-day drug free interval. This schedule was repeated every 4 weeks.,Docetaxel, cisplatin, UFT and,20,Results,72 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 observed 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 stimulating 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).,Results72 patients received 26,21,Conclusions,These results suggests that the combination of docetaxel, 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.,ConclusionsThese results sugge,22,Oxaliplatin-based regimen as neoadjuvant chemotherapy for Chinese patients with advanced gastric cancer: Preliminary results of a phase II study.,AbstractNo:4184,J.-F. Ji,; University School of Oncology, Beijing Cancer Hospital, Beijing, China; Beijing Cancer Hospital, Beijing, China,Methods:,15 pts (Stage IIIb or IV) have been enrolled by now. All pts had histologically proven gastric adenocarcinoma and no previous 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 was evaluated after 2 cycles.,Oxaliplatin-based regimen as n,23,Results,All 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 2-6 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 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 meeting.,ResultsAll pts are evaluable f,24,Conclusions:,In view of the favorable response rate and toxicity profile, this protocol will be further assessed in a multicenter phase II trial.,Conclusions:In view of the fav,25,Phase II study of weekly paclitaxel in patients with advanced gastric cancer in Japan.,AbstractNo:4226:,H. Baba,; Kyushu University, Fukuoka, Japan; Hiroshima Red Cross Hospital, Hiroshima, Japan,Methods:,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-infusion paclitaxel of 80mg/m2 with a short premedication for consecutive 3 weeks with one week rest as one course.,Phase II study of weekly pacli,26,Results,Patients 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 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 in 17.3%, 16.4%, 23.1%, and 47.6%, respectively,ResultsPatients characteristic,27,Conclusions,Weekly 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.,ConclusionsWeekly paclitaxel w,28,Docetaxel-cisplatin-5FU (TCF) versus 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).,AbstractNo:4020:,A. D. Roth, Oncosurgery, Geneva University Hospital, Geneva, Switzerland;,Methods:,Patients (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 (epirubicin 50mg/m2, cisplatin 60mg/m2, 5-FU CI 200mg/m2/d for 3w).,Docetaxel-cisplatin-5FU (TCF),29,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 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 decrease docetaxel from 85 to 75mg/m2 in TC and TCF, resulting in lesser FN occurence. Grade 3 non-hematologic toxicity was infrequent (10% of pts) apart from alopecia (3 arms), nausea (18% in TC and TCF pts) and diarrhea (15% in TCF pts).,Results:Among 121pts enrolled,30,Conclusions:,Despite an increased toxicity, docetaxel based regimens seem to be more efficacious than ECF. In terms of RR and TTP, TCF is the more promising regimen and should be chosen for formal comparison with ECF. This trial is supported in part by Aventis,Conclusions:Despite an increa,31,Multicentric phase II study of epirubicin and docetaxel as first line treatment for patients with advanced gastric cancer: A GERCOR study.,AbstractNo:4062:,S. Nguyen,Centre Hospitalier de Beauvais, Beauvais, France,;,Methods:,36 patients (7 females,29 males; performance status PS 0/1/2: 12/8/6, LA/M: 7/29; mean weight: 69,6 kg) were treated with epirubicin 60 mg/m2 in 30 minutes, followed 1 h later by docetaxel 75 mg/m2 in 60 minutes, every 21 days, in an outpatient basis . Corticosteroids were administered from day-1 to day 4, and GCSF recommended from day 3 to day 9. All patients were assessable for toxicity (NCI-CTC criteria) and efficacy (Recist evalution criteria). Patients were evaluated every 3 cycles (2 months), and 5FU + platinium-based second-line treatment was recommended at progression,Multicentric phase II study of,32,Results:,174 cycles were administered (median 5, range 1-9). No toxic death was reported. Grade 3-4 toxicities were: neutropenia in 41,7% of patients,thrombocytopenia in 5,6%, anemia in 11,1%, nausea-vomiting in 13,9% and diarrhea in 5,6%. Median PS and mean weight remained unchanged at first evaluation. Symptoms (including pain,anorexia and dysphagia ) were improved at first evaluation in one-third of patients with initial symptoms. 1 complete response (CR) (2,7%) and 6 partial response (PR) (16.7%) were obtained , for an overall response (OR) rate of 19,4% (95% CI: 0,07-0,32). 10 patients (27,8%) had stable disease, and 19 patients (52,8%) progressed. Two-third of patients received second-line therapy. With a median follow-up time of 100 weeks, the median PFS and OS times were 18 and 52 weeks , respectively.,Results:174 cycles were admini,33,Conclusions:,First-line efficacy of EPITAX combination is in the same range as that observed in second-line, with an acceptable toxicity. 1-yr overall survival may be related to the therapeutic strategy including early evaluation and active second-line therapy.,Conclusions:First-line efficac,34,A phase II study of Oxaliplatin with ELF regimen in patients with advanced gastric cancer,AbstractNo:4206,Hong-Ming Pan,1, Nong Xu,2, Fang Lou,1,Yong Guo,3,Wei Jin,1, Hai-Zhou Lou,1, Yu Zheng,1,Wei-jia Fang,2,1.Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University;,2.Chemotherapy Department, the 1st hospital affliated to Zhejiang University;,3. Oncology department, Zhejiang traditional Chinese Hospital;,Hangzhou,310016, Zhejiang Province, China,A phase II study of Oxaliplati,35,Louvet, C.; Andr, T.; Tigaud, J.M ,et al,.Phase II Study of Oxaliplatin, Fluorouracil, and Folinic Acid in Locally Advanced or Metastatic Gastric Cancer Patients.,Journal of Clinical Oncology,20(23):4543-4548 ,2002,Best responses in the 49 assessable patients were two complete responses and 20 partial responses, giving,an overall best response rate of 44.9%.,Eight patients underwent complementary treatment with curative intent (six with surgery and two with chemoradiotherapy).,Median follow-up 18.6 months,TTP 6.2 months, and overall survival 8.6 months.,Louvet, C.; Andr, T.; Tigaud,36,Kim DY , Kim JH , Lee SH et al.,Phase II study of oxaliplatin, 5-fluorouracil and leucovorin in previously platinum-treated patients with advanced gastric cancer.,Annals of Oncology,14:383-387, 2003,Of the 23,evaluable,patients, there were six partial responses,(response rate 26%).,All responding patients were among those who,entered,into this trial immediately after failure of previous chemotherapy with,5-FU and cisplatin,.,The median TTP was 4.3 months and the median overall survival was 7.3 months,.,Grade 12 anemia in 39 cycles (39%). No grade 4 leukopenia or thrombocytopenia were observed. nausea/vomiting (33%). Peripheral neuropathy of grade 1 or 2 was noted (27%), but there was no grade 3 or 4 neurotoxicity.,Kim DY , Kim JH , Lee SH et al,37,Our Study Design,A phase II studywas conducted to evaluate the efficacy and safety of the combination of Oxaliplatin and ELF regimen in the treatment of patients with advanced gastr