胃癌课件英文Gastric Cancer.ppt
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Chemotherapy in Gastric Cancer
GASTRIC CANCER
Worldwide incidence*
? 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).
? 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.
? Nearly 70% to 80% of resected gastric carcinoma specimens have metastases inthe regional lymph nodes. Thus, it is common to encounter patientswith advanced gastric carcinoma at the outset.
? In the Western Hemisphere, R0resection 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 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 furtherclassified: (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).
Global Consensus
? Good local control is essential to cure gastric carcinoma
? The only potentially curative treatment for localized gastric cancer is surgery.
Chemotherapy of Gastric Cancer
? 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
? 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.
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.
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
? Several randomized studies comparing FAM versus FAMTX (5- FU, adriamycin, and methotrexate [with leucovorin rescue), FAMTXversus 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
? 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.
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 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 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.......（后略) ......
Chemotherapy in Gastric Cancer
GASTRIC CANCER
Worldwide incidence*
? 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).
? 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.
? Nearly 70% to 80% of resected gastric carcinoma specimens have metastases inthe regional lymph nodes. Thus, it is common to encounter patientswith advanced gastric carcinoma at the outset.
? In the Western Hemisphere, R0resection 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 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 furtherclassified: (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).
Global Consensus
? Good local control is essential to cure gastric carcinoma
? The only potentially curative treatment for localized gastric cancer is surgery.
Chemotherapy of Gastric Cancer
? 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
? 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.
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.
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
? Several randomized studies comparing FAM versus FAMTX (5- FU, adriamycin, and methotrexate [with leucovorin rescue), FAMTXversus 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
? 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.
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 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 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.......（后略) ......
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