title: Prospective randomized trial of combined oncological therapy for gastric carcinoma Adjuvant chemotherapy for resectable gastric cancer: a preliminary report. A follow-up study on chemoimmunotherapy (5-fluorouracil and BCG) in advanced gastric cancer A randomized trial comparing adjuvant fluorouracil, epirubicin, and mitomycin with no treatment in operable gastric cancer. Preoperative immunostimulation with propionibacterium avidum KP-40 in patients with gastric carcinoma: a prospective randomized study. Randomly controlled study of chemotherapy versus chemoimmunotherapy in postoperative gastric cancer patients. Postoperative morbidity and mortality after D1 and D2 resections for gastric cancer: preliminary results of the MRC randomised controlled surgical trial Postoperative adjuvant 5‐fluorouracil plus methyl‐CCNU therapy for gastric cancer patients. Eastern cooperative oncology group study (EST 3275) Prospective randomized trial of early postoperative intraperitoneal chemotherapy as an adjuvant to resectable gastric cancer. Combined 5-fluorouracil and radiation therapy as a surgical adjuvant for poor prognosis gastric carcinoma. Positive results of adjuvant mitomycin-C in resected gastric cancer: a randomised trial on 134 patients. Clinical evaluation of schizophyllan adjuvant immunochemotherapy for patients with resectable gastric cancer —A randomized controlled trial— Use of 5‐fluorodeoxyuridine (FUDR) as an adjuvant to the surgical management of carcinoma of the stomach Prospective, double-blind, placebo-controlled randomized trial of cimetidine in gastric cancer Levamisole in postoperative adjuvant immunochemotherapy for gastric cancer Efficacy of prolonged intermittent therapy with combined 5‐FU and methyl‐CCNU following resection for gastric carcinoma. A veterans administration surgical oncology group report Adjuvant chemotherapy after gastric resection in node-positive cancer patients: a multicentre randomised study. Postoperative adjuvant immunotherapy of gastric cancer with BCG-cell wall skeleton Randomized clinical trial on the combination of preoperative irradiation and surgery in the treatment of adenocarcinoma of gastric cardia (AGC)--report on 370 patients. The effect of adjuvant chemotherapy in gastric carcinoma is dependent on tumor histology: 5-year results of a prospective randomized trial. Adjuvant intraperitoneal chemotherapy with carbon-adsorbed mitomycin in patients with gastric cancer: results of a randomized multicenter trial of the Austrian Working Group for Surgical Oncology. Adjuvant chemotherapy with 5-FU, adriamycin, and mitomycin-C (FAM) versus surgery alone for patients with locally advanced gastric adenocarcinoma: A southwest oncology group study [Evaluation of postoperative immunotherapy of gastric cancer]. Comparison of 5-fluorouracil with ftorafur in adjuvant chemotherapies with combined inductive and maintenance therapies for gastric cancer. Adjuvant intraperitoneal cisplatin therapy in patients with operated gastric carcinoma: results of a randomized trial. [A randomized controlled trial of surgical adjuvant therapy with mitomycin C, 5-fluorouracil and OK-432 in patients with gastric cancer]. Controlled trial of adjuvant chemotherapy following curative resection for gastric cancer Chemotherapy for operable gastric cancer: results of the Dutch randomised FAMTX trial. The Dutch Gastric Cancer Group (DGCG). A randomized clinical trial of adjuvant chemotherapy after resection in patients with stomach cancer. The second British Stomach Cancer Group trial of adjuvant radiotherapy or chemotherapy in resectable gastric cancer: five-year follow-up Gastric carcinoma treated by chemotherapy after resection: a controlled study. [Adjuvant intraoperative radiotherapy of stomach carcinoma]. A randomized trial comparing adjuvant fluorouracil, doxorubicin, and mitomycin with no treatment in operable gastric cancer. International Collaborative Cancer Group. Adjuvant 5-fluorouracil and BCNU chemotherapy in gastric cancer: 3-year results. Upper abdominal stop-flow perfusion as a neo and adjuvant hypoxic regional chemotherapy for resectable gastric carcinoma. A prospective randomized clinical trial. A prospective, randomized evaluation of intensive‐course 5‐fluorouracil plus doxorubicin as surgical adjuvant chemotherapy for resected gastric cancer Adjuvant intraperitoneal cisplatin chemotherapy does not improve long-term survival after surgery for advanced gastric cancer. Intraperitoneal thermochemotherapy for prevention of peritoneal recurrence of gastric cancer. Final results of a randomized controlled study Long-term follow-up study of gastric cancer patients treated with surgery and adjuvant chemotherapy with mitomycin C. Adjuvant treatments following curative resection for gastric cancer Adjuvant mitomycin and fluorouracil followed by oral uracil plus tegafur in serosa-negative gastric cancer: a randomised trial Mitomycin C as an Adjuvant in Resected Gastric Cancer [Cooperative study on surgical adjuvant immunochemotherapy for prevention of postoperative recurrence of gastric cancer (II). Cooperative study group on surgical adjuvant immunochemotherapy for prevention of postoperative recurrence of gastric cancer supported by the Ministry of Health and Welfare ( Final results of a phase III clinical trial of adjuvant chemotherapy with the modified fluorouracil, doxorubicin, and mitomycin regimen in resectable gastric cancer. Randomized clinical trial of adjuvant mitomycin plus tegafur in patients with resected stage III gastric cancer. ADJUVANT CHEMOTHERAPY IN OPERABLE GASTRIC CANCER: 5 Year Follow-up of First British Stomach Cancer Group Trial Prophylaxis with carbon-adsorbed mitomycin against peritoneal recurrence of gastric cancer Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer.
abstract: One hundred forty‐two patients with all stages of gastric carcinoma were prospect ively stratified into two divisions according to T.N.M. stage following , but irrespective of the type of surgical procedure . Division I ( T 1‐3 , N 1‐2 , M O ) was r and omized into a control group , and a treatment group who received 2000 rad in 8 fractions over 10 days with intravenous 5 Fluorouracil ( 5 F.U. ) at a dose of 500 mg daily × 4 days preirradiation and then 12.5 mg/kg daily for 5 days every 28 days for six courses . Division II ( T4 or M1 ) was r and omized into three groups ; a control group , a group who received radiotherapy and 5 F.U. in the same schedule as division one and a group who received Thiotepa 45 mg intravenously daily for three days and then every 28 days for 6 months . Four and one‐half years after commencement of the trial 86 % of the patients had died . There was no difference in survival rate between the treatment and control groups , ( p > 0.5 ) in Division I or II . Survival appeared to correlate with the T.N.M. stage of disease and not therapy . Blind assessment of the quality of life showed no difference between the treatment groups and the controls . In the dose schedules used , this form of oncological therapy had no efect on survival or quality of life in patients with gastric carcinoma . Cancer 44:385‐391 , 1979 In this prospect ively r and om study , the effect of oral Ftorafur as an adjuvant chemotherapy was compared with that of oral placebo in patients with Stage II and Stage III gastric cancer . Patients had undergone a subtotal gastrectomy with a resection margin that should have been free of tumors .  Ftorafur ( 10 mg/kg ) was given daily to 59 Group A patients .  Multiple vitamins were given twice a week to 56 Group B patients . We found that there was no statistical significance in Stage II patients with regard to survival . In Stage III patients , those treated with oral Ftorafur had better 3-year and 5-year survival rates than those receiving oral placebo . This preliminary report on this ongoing study seems to indicate that long-term postoperative Ftorafur treatment may be beneficial to Stage III gastric cancer patients Summary Two hundred and seventeen patients with advanced gastric cancer were classified according to the resectability of the tumour into two groups : I , resectable ( non-radical surgery ) , 99 patients , and II , non-resectable carcinoma , 118 patients . Within each group patients were r and omly assigned to receive 5-fluorouracil ( 5-FU ) + BCG , 5-FU , or no further treatment ( surgery only ) . BCG was given by scarification . A 2-year follow-up is reported . The group of patients with resectable tumours and receiving chemoimmunotherapy had a statistically significant prolongation of survival compared with the 5-FU and surgery only groups . No differences in survival were observed between these treatment modalities in patients with non-resectable tumour . These observations indicate that chemoimmunotherapy may be of benefit for a selected group of patients with gastric cancer Combination chemotherapy ( CT ) has , in some groups of patients with gastric cancer ( GC ) , who are at a high risk for relapse , result ed in a small but measurable improvement in palliation and patient survival not reaching statistical significance and therefore remaining applicable in an investigational setting . Based on the above data , we studied adjuvant CT with FEM ( 5-fluorouracil ( 5-FU ) , epirubicin , mitomycin C ) in a r and omized study of patients with completely resected stage III GC and patients with stages T1 - 3 with a low histologic grade .  CT was started 2 - 3 weeks after surgery . From August 1988 until February 1994 , 84 patients with completely resected tumors and lymph nodes were r and omized to either group A  ( FEM ) or group B ( no treatment ) .  Patients were eligible for r and omization if they had a Karnofsky score > 60 , no postoperative evidence of residual tumor , and normal cardiac , hepatic and renal functions . Forty-two patients were r and omized to each group , with no significant differences regarding : age distribution , group A 53 years ( 41 - 65 ) , group B 57 years ( 35 - 66 ) ; sex , group A 32/10 , group B 25/17 ( men/women ) ; site of primary tumor , group A 22/20 , group B 25/17 ( pylorus/antrum ) ; histologic grade , group A 0/19/23 , group B 0/25/17 ( grade s I/II/III ) ; lymph node metastases , group A 30 , group B 32 , and surgical procedure , group A 33/9/6 , group B 35/7/9 ( total gastrectomy/partial gastrectomy/splenectomy ) . Group A received 5-FU 600 mg/m2/day i.v . on days 1 , 8 , 29 and 36 , epirubicin 45 mg/m2/day i.v . on days 1 and 29 , and mitomycin C 10 mg/m2 i.v . on day 1 . The schedule was repeated every 56 days for 3 cycles . Group B received no treatment odd was only subjected to the regular follow-up . At the last follow-up at 66 months , 27/42 patients in group A ( 64 % ) had relapsed or died , compared to 34/42 patients in group B ( 81 % ) . The differences in the relapse and the disease-free and the overall survival rates were not statistically significant . Only the subgroup of patients with histologic grade III tumors receiving adjuvant FEM  demonstrated a trend towards improved survival ( p = 0.085 ) . Main therapy-related toxicities for the treatment group were grade I-II anemia , neutropenia , and throbocytopenia in 16 , 45 , and 22 % of patients , respectively , and grade I-II nausea and vomiting in 29 % of patients . Based on the present findings and those of previous studies , even if one considers the difference reaching statistical significance in the latter for histologic grade III tumors , it becomes evident that with current therapeutic modalities adjuvant therapy has no established role in the management of resectable GC . Studies of new-generation regimens , such as FAMTX ( 5-FU , Adriamycin and methotrexate ) as well as ELF ( etoposide , Leucoverin , and 5-FU ) , should be conducted in the adjuvant therapy setting with a nontherapy control group , in order to clarify the issue of adjuvant CT in resectable GC Sixty-eight patients admitted for resection of gastric carcinoma entered a prospect ively r and omized trial . Patients in the therapy group ( n = 34 ) received a preoperative controlled infusion of 10 mg Propionibacterium avidum KP-40 . The therapy and control group did not differ with regard to postoperative complications , tumor recurrence rates ( therapy group : 41 % , control group : 38 % ) , and patient survival rates ( survival rate in the therapy group after 25 months : 53 % , in the control group after 25 months : 50 % ) From September 1979 through March 1981 , a total of 302 patients with gastric cancer and undergoing gastrectomy at the Department of Surgery at Chiba University Hospital and its 14 affiliated hospitals was studied for clinical effectiveness of immunotherapy with Nocardia rubra cell wall skeleton . The patients were stratified by gross stage of cancer and degree of operative curability . They were then assigned r and omly to either chemotherapy group or chemotherapy plus immunotherapy group . Immunotherapy used was intradermal injection of 400 micrograms of N. rubra cell wall skeleton which was given weekly for the first month and monthly thereafter . After the specimen was examined microscopically , the patients were classified by histological stage of cancer and radicality of surgical intervention into curative or noncurative groups . The patients were surveyed for survival period in December 1981 . The postoperative survival rate was compared in patients of histologically curative or noncurative resection cases between the two treatment groups . No statistical difference was detected between the groups in age , sex , or operative procedures that might influence the patient 's survival . As a result , statistical intergroup difference in survival rates was not seen in patients of the curative group , probably due to a short observation period . However , the intergroup difference in survival rates was statistically significant in patients of the noncurative group ( p less than 0.01 ) . These results indicate the adjunctive effect of N. rubra cell wall skeleton as an immunotherapeutic agent in patients undergoing gastrectomy for gastric cancer BACKGROUND In Japan the surgical approach to treatment of potentially curable gastric cancer , including extended lymphadenectomy , seems in retrospective surveys to give better results than the less radical procedures favoured in Western countries . There has , however , been no evidence from r and omised trials that extended lymphadenectomy ( D2 gastric resection ) confers a survival advantage . This question was addressed in a trial involving thirty-two surgeons in Europe . METHODS In a prospect i ve r and omised controlled trial , D1 resection ( level 1 lymphadenectomy ) was compared with D2 resection ( levels 1 and 2 lymphadenectomy ) . Central r and omisation ( 200 patients in each arm ) followed a staging laparotomy . FINDINGS The D2 group had greater postoperative hospital mortality ( 13 % vs 6.5 % ; p=0.04 [ 95 % Cl 9 - 18 % for D2 , 4 - 11 % for D1 ] and higher overall postoperative morbidity ( 46 % vs 28 % ; p<0.001 ) ; their postoperative stay was also longer . The excess postoperative morbidity and mortality in the D2 group was accounted for by distal pancreaticosplenectomy and splenectomy . In the whole group ( 400 patients ) , survival beyond three years was 30 % in patients whose gastrectomy included en-bloc pancreatico-splenic resection versus 50 % in the remainder . INTERPRETATION D2 gastric resections are followed by higher morbidity and mortality than D1 resections . These disadvantages are consequent upon additional pancreatectomies and distal splenectomies , and in long-term follow-up the higher mortality when the pancreas and spleen are resected may prove to nullify any survival benefit from D2 procedures After en bloc resection of gastric adenocarcinoma , 180 patients were r and omized to 2 years of 5‐fluorouracil ( 5‐FU ) + semustine ( MeCCNU ) chemotherapy or to observation only . After a median follow‐up time of 64 months , 48 of 89 control patients and 51/91 treated patients recurred ( P < 0.71 ) . The sites of recurrent cancer were similar for both groups : liver , 32 % ; local esophagus or stomach , 51 % ; abdominal nodes and peritoneum , 38 % ; and extra‐abdominal nodes , 14 % . The survival curves overlap ; 51/89 controls and 57/91 treated patients died with a median survival of 32.7 and 36.6 months , respectively ( P < 0.73 ) . Treated patients experienced clinical ly important hematologic toxicity and two treated patients died of marrow failure with leukemia . Because of the toxicity and the lack of effectiveness , adjuvant 5‐FU + MeCCNU is not recommended for patients with resectable gastric cancer OBJECTIVE Surgeons have postulated on numerous occasions that cancer resection may participate in the dissemination of a malignancy . This r and omized trial sought to determine whether a large volume of chemotherapy solution used perioperatively to flood the peritoneal cavity could eliminate microscopic residual disease and thereby improve survival of patients with gastric cancer . SUMMARY BACKGROUND DATA Surgical treatment failures in patients with gastric cancer are confined to the abdomen in most patients . Resection site and peritoneal surface spread , along with liver metastases , are the most common areas of recurrence . Survival and quality of life of patients with gastric cancer would be improved if disease progression at these anatomic sites was reduced . METHODS In a prospect i ve r and omized trial of 248 patients , intraperitoneal mitomycin C on day 1 and intraperitoneal 5-fluorouracil on days 2 through 5 were administered after gastric cancer resection .  Patients who were thought to have stage II or stage III disease were r and omized after resection to surgery alone versus surgery plus early postoperative intraperitoneal chemotherapy . After final pathologic examinations , there were 39 patients with stage I , 50 with stage II 95 with stage III , and 64 with resected stage IV cancer . RESULTS The 5-year survival of the surgery-only group was 29.3 % , and the surgery-plus-intraperitoneal chemotherapy group was 38.7 % ( p = 0.219 ) . In a subset analysis , the patients with stage I , stage II , and stage IV disease showed no statistically significant difference in survival . The 5-year survival rate of patients with stage III disease who underwent surgery only was 18.4 % versus a survival rate of 49.1 % for patients who underwent surgery plus intraperitoneal chemotherapy ( p = 0.011 ) . CONCLUSIONS In a subset analysis , patients with stage III gastric cancer have shown a statistically significant improvement in survival when treated with perioperative intraperitoneal chemotherapy . Further studies in patients with gastric cancer with surgically directed chemotherapy are suggested Sixty-two patients with resectable but poor-prognosis gastric carcinoma were r and omized to either no surgical adjuvant therapy or treatment with 5-fluorouracil ( 15 mg/kg by rapid intravenous injection X 3 ) plus radiation ( 3,750 rad in 24 fractions ) initiated 3 1/2 to six weeks postoperatively . Informed consent was obtained after r and omization and only from the 39 r and omized to treatment . Ten patients refused their treatment assignment . The five-year survival rate for patients r and omized to treatment was 23 % , and for those r and omized to no treatment , 4 % ( P less than .05 ) . Both the survival distributions and the alive-without-recurrence distributions were significantly different for the two groups ( P = .024 ) and favored treatment assignment . When the treatment assignment group was broken down to those patients actually receiving treatment and those refusing , five-year survival rates were : treated , 20 % ; treatment refusal , 30 % ; controls , 4 % ; the three survival distributions were not significantly different . Thirty-nine percent of patients actually treated had a local-regional component of first clinical recurrence compared with 54 % of those who received no treatment . This study does not establish 5-fluorouracil plus radiation  as effective surgical adjuvant therapy  for gastric cancer but suggests this approach as a possible fruitful area for continued research . This study also illustrates the potential problems that may be encountered in interpreting results when patients are r and omized to a study before consent is obtained In order to evaluate the results on successful adjuvant chemotherapy in resected gastric cancer we performed a r and omised trial on 134 patients in two arms : a control one with no further treatment after surgery versus a treatment arm given mitomycin-C ( MMC ) , 20 mg/m2 intravenously one day every 6 weeks for four courses , starting before the sixth week after surgery . The median follow-up was 105 months . In the control arm , 49 out of 66 patients died due to recurrence , versus 40 out of 68 patients in treatment arm .  Actuarial survival curve was statistically significant ( P < 0.025 ) in favour of the treatment group . Liver metastases were lower in adjuvant group than in the control group ( 8/68 versus 19/66 ) . Toxicity was mild . Main toxic effects were thrombocytopenia , leukopenia , nausea and vomiting . A pelvis renal cancer as a second malignancy 8 years after gastric cancer was observed . In that particular case MMC was given after surgery . We conclude that adjuvant chemotherapy based on MMC given in the early period after surgery , improves survival rate in gastric cancer resected patients Adjuvant immunochemotherapy using schizophyllan ( SPG ) , an extract from the culture broth ofSchizophyllum commune Fries , was prescribed at r and om for 326 Japanese patients with resectable gastric cancer . The overall survival rates for 3 years did not differ between the SPG and control groups . In 62 patients with stage I gastric cancer and 67 with stage II , there was little difference in the 3-year survival rates . The survival rates for 100 patients with stage III were enhanced at p=0.0811 in the SPG group , as compared to the controls . The survival rates in 97 patients with stage IV cancer were much the same . These results warrant further application of this immunopotentiating drug for treating patients with resectable gastric cancer 5‐Fluorodeoxyuridine was administered to 185 patients r and omized to the treated group following gastric resection for carcinoma of the stomach . Two hundred twelve patients were r and omized to control groups . There are no significant differences in operative mortality , complications , or 3‐year survival rates Summary Cimetidine is thought to inhibit suppressor T-lymphocyte function and preliminary evidence from a r and omized trial indicated that it might prolong survival for patients with operable and inoperable gastric cancer . The British Stomach Cancer Group conducted a r and omized , double-blind , placebo-controlled trial examining the effects of cimetidine ( 400 mg or 800 mg twice a day ) on the survival of patients with early ( stages I , II and III : n = 229 ) and advanced ( stages IVa and IVb : n = 201 ) gastric cancer . The primary end point was death . A total of 442 patients were r and omized by 59 consultants in 39 hospitals between February 1990 and March 1995 .  Log-rank survival analysis was used to assess differences between the groups . Three hundred and forty patients  died during the study : 166 ( 49 % ) in the cimetidine treatment groups and 174 ( 51 % ) in the placebo groups . Median survival for patients receiving cimetidine was 13 months ( 95 % confidence interval ( CI ) 9–16 months ) and 11 months in the placebo arm ( 95 % CI 9–14 months ) . There was no significant difference in survival between the two treatment groups ( P = 0.42 ) or between different doses of cimetidine tablets ( P = 0.46 ) . Five-year survival of those patients r and omized to cimetidine was 21 % compared to 18 % for those patients r and omized to placebo . Cimetidine at a dose of 400 mg or 800 mg twice a day does not have a significant influence on the survival of patients with gastric cancer compared to placebo Summary The usefulness of LMS in postoperative immunochemotherapy of gastric cancer was investigated . In compliance with the protocol , MMC was given at a dose of 20 mg on the day of gastrectomy , and an additional 10 mg on the next day IV . The patients receiving 600 mg Tegafur daily were then divided into two groups according to whether LMS was also given or not . LMS was administered for 3 days before the operation in a daily dose of 150 mg and for 1 year or more after operation according to a schedule of 3 days ' administration followed by an 11-day interval . The 2-year follow-up demonstrated that in stage III patients , the LMS ( + ) regimen was superior to the LMS ( − ) regimen , since the former prolonged the relapse-free interval significantly . The survival rate for stage III disease was also significantly higher in the LMS ( + ) than in the LMS ( − ) group . There was no significant difference in the incidence of subjective or objective side-effects between two groups . The incidence of agranulocytosis was comparable in the two groups This prospect i ve evaluation of 5‐fluorouracil ( 5‐FU ) and methyl‐CCNU administered in combination to patients with surgery for histologically proved gastric adenocarcinoma is based upon 312 patients r and omized between August 1974 and May 1980 . Patients were stratified into three categories of resectability , ( 1 ) complete , ( 2 ) proven incomplete , and ( 3 ) nonresectable , prior to r and om treatment assignment to  surgery alone  or surgery followed by adjuvant chemotherapy . Drug therapy consisted of discrete 5‐day courses administered at 7‐week intervals . Toxic reactions were reported in association with 42 % of the courses . Treatment was suspended or discontinued in 6 % of the courses because of hematologic toxicity . Treated patients with curative resections experienced a more favorable survival than did controls , but the early advantage was lost by the end of the second follow‐up year . However , no statistically significant improvements in survival or reductions in risks of recurrence were observed . Similar proportions of treated and control deaths were attributable to residual or recurrent disease After curative resection for gastric adenocarcinoma , 103 patients , all with positive nodes , were r and omised so that 48 received adjuvant chemotherapy of epidoxorubicin ( EPI ) 75 mg m-2 on day 1 , leucovorin ( LV ) 200 mg m-2 on days 1 - 3 and 5-fluorouracil ( 5-FU ) 450 mg m-2 on days 1 - 3 , every 21 days for 7 months , whereas the remaining 55 did not . During the first year of observation , 21 control patients ( 38 % ) and five treated patients had recurrences . After a follow-up period of 36 months , 12 of the treated patients ( 25 % ) and only seven controls ( 13 % ) were still alive . At that point , the median survival was 13.6 months for the 55 untreated patients and 20.4 months for the 48 treated patients , a significant difference . We found a survival advantage for patients treated with the EPI-LV-5-FU regimen and a consistent delay in the appearance of recurrent or metastatic cancer . Acute toxicity was mild and treatment was well accepted by all patients . There was no long-term toxicity or any cardiac toxicity . We conclude that this particular chemotherapy , administered shortly after gastric resection , improves survival rate in node-positive gastric cancer patients , even although final assessment of this particular adjuvant approach must await completion of the trial Summary The clinical effectiveness of immunotherapy with the cell wall skeleton of Bacillus Calmette-Guérin was assessed in a study involving 140 consecutive patients with gastric cancer , who were gastrectomized at a single institution from January 1976 through December 1978 . These patients were r and omized by an envelope method after operation and divided into three treatment groups : ‘ control ’ , ‘ chemotherapy ’ , and ‘ chemotherapy plus immunotherapy with BCG-CWS . ’ Only two patients who died during surgery were excluded , and a survey of survival periods was made on the remaining 138 patients in January 1982.As a result , statistically significant differences in the survival rate curve were observed between the control and chemotherapy plus immunotherapy groups ( P<0.01 ) , and between the chemotherapy and chemotherapy plus immunotherapy groups ( P<0.05 ) . These results emphasize effectiveness of BCG-CWS as an adjuvant immunotherapeutic agent in gastrectomized cancer patients PURPOSE An attempt was made to define the role of radiotherapy before operation for AGC . METHODS AND MATERIAL S From January 1978 to May 1989 , a prospect i ve r and omized trial on preoperative radiotherapy ( R+S ) vs. surgery alone ( S ) for AGC was carried out in 370 patients . Patients were r and omized into a combined group ( R+S , 171 patients ) or a surgery alone group ( S , 199 patients ) by the envelope method . 8-MV photon or telecobalt was used for the preoperative radiation therapy , using anterior-posterior opposing parallel fields to deliver 40 Gy to the cardia , lower segment of the esophagus , fundus , lesser curvature , and hepatogastric ligament . Surgery was performed after 2 to 4 weeks rest . RESULTS The 5- and 10-year survival rates of the R+S Group and the S Alone Group were 30.10 % and 19.75 % , 20.26 % and 13.30 % , respectively . The survival curves of these two groups diverged right from the beginning after the operation over the ninth year . Statistics by Kaplan-Meier log rank test proves that the difference is significant ( chi2 = 6.74 , p = 0.0094 ) . The immediate results were : resection rate 89.5 % and 79.4 % ( p < 0.01 ) ; pathologic stage after resection T2 12.9 % and 4.5 % ( p < 0.01 ) , T4 40.3 % and 51.3 % ( p < 0.05 ) , lymph node metastasis rates 64.3 % and 84.9 % ( p < 0.001 ) ; operative mortality rates 0.6 % and 2.5 % ; intrathoracic leak rates 1.8 % and 4.0 % , respectively . The causes of failure were : local uncontrol and recurrence 38.6 % vs. 51.7 % ( p < 0.025 ) , regional lymph node metastasis 38.6 % vs. 54.6 % ( p < 0.005 ) , distant metastasis 24.3 % vs. 24.7 % . CONCLUSION Preoperative radiation therapy is able to improve the results of surgery for adenocarcinoma of the gastric cardia Gastric carcinoma is decreasing in incidence in Western Europe and the United States . However , this disease is still a major cause of cancer death [ 1 ] . Extended surgical procedures over the past 20 years have not profoundly altered the poor outcome of patients with gastric carcinoma [ 2 ] . This fact indicates that surgery alone may not be enough to control the disease . In 1978 we began a prospect i ve r and omized , one-center trial to determine , whether postoperative treatment with mitomycin C ( MMC ) , 5-fluorouracil ( 5-FU ) , and cytosine-arabinoside ( Ara-C ) given for three courses could substantially improve the overall survival of patients treated by curative resection for gastric carcinoma . The regimen employed had been shown to be the most effective chemotherapy combination at the time the study started [ 3 ] . At a median follow-up of 5 years we found no significant effect of adjuvant chemotherapy on overall survival compared with an untreated control group . However , in a retrospective subgroup analysis we observed a significant improvement in the overall survival of patients with the intestinal tumor type , but no effect in patients with mucocellular carcinoma . We therefore believe that there is a selective effect of adjuvant chemotherapy in patients with gastric carcinoma with intestinal type of tumors PURPOSE Previous studies have demonstrated a beneficial effect of intraperitoneally applied mitomycin bound to activated carbon particles ( M-CH ) in preventing intraabdominal recurrence following curative surgery for gastric cancer . The Austrian Working Group for Stomach Cancer , a subgroup of the Austrian Working Group for Surgical Oncology , initiated a multicentric phase III trial to evaluate the safety and efficacy of this treatment regimen . PATIENTS AND METHODS A total of 91 patients with a radically resected gastric cancer infiltrating the serosal surface were r and omly assigned to receive either 50 mg mitomycin bound to a solution of 375 mg carbo adsorbens intraperitoneally before closure of the abdominal wound ( n = 46 ) or served as a surgical control group ( n = 45 ) . Postoperative complications and recurrence-free and overall survival were evaluated to analyze the risks and benefits of this treatment . RESULTS After a median observation period of 597 days ( range , 72 to 1,096 ) , a significantly higher postoperative complication rate was observed in the M-CH group ( 35 % ) compared with the control group ( 16 % ) ( P < .02 ) . In accordance with this finding , the postoperative ( 60 days ) mortality rate was also significantly elevated in the M-CH group ( 11 % v 2 % in the control group ) . Since analysis of overall and recurrence-free survival failed to show any beneficial effect of M-CH therapy , the protocol committee decided to stop further recruitment of patients onto this study . CONCLUSION Adjuvant intraperitoneal therapy of gastric cancer by mitomycin bound to activated carbon particles is associated with an increased rate of postoperative complications . However , no benefit for prognosis following radical resection of locally advanced tumors was observed in this multicenter phase III trial Abstract Purpose : To evaluate FAM [ 5-FU ( 5-fluorouracil ) , doxorubicin , mitomycin C ] chemotherapy as adjuvant therapy for patients with resected TNM stage I , II , or III gastric carcinoma . Patients and Methods : One hundred ninety-three eligible patients were accrued from 1978 to 1991 in a phase III trial comparing six cycles ( 1 year ) of postoperative FAM chemotherapy with observation only . Results : The median follow-up on this study was 9.5 years . For all patients , no differences ( log-rank analysis ) in disease-free survival ( p=0.45 ) and overall survival ( p=0.57 ) between FAM therapy ( 93 cases ) and surgery ( 100 cases ) were observed . Quality of surgical resection affected survival irrespective of FAM use . Cases with curative resection , defined in a retrospective review of pathology and surgical reports as cases having no evidence of residual disease in the abdomen and tumor-free margins > 1 cm , had superior survival compared to cases not meeting these requirements ( p<0.001 ) . FAM was well tolerated with 6 % ( five of 90 ) of cases demonstrating grade IV hematologic toxicity . There were two drug-related fatalities ( one cardiomyopathy , one hematolytic uremic syndrome ) . Conclusion : FAM is not effective adjuvant therapy for TNM stage I , II , and III patients with resected gastric cancer . Future adjuvant studies must emphasize prospect i ve surgical quality control to assure enrollment of appropriately staged and resected cases and wide participation to assure adequate case accrual over a reasonable period In order to evaluate the clinical effectiveness of immunotherapy on gastric cancer patients , we performed two controlled trials of immunotherapy with BCG-CWS and Nocardia rubra CWS respectively . A controlled trial of BCG-CWS was performed from 1976 to 1978 . The result showed an improved survival rate of the immunotherapy as compared with the chemotherapy group . From September 1979 through March 1981 , a total of 302 patients with gastric cancer undergoing gastrectomy at the Department of Surgery , Chiba University Hospital and its 14 affiliated hospitals were studied for clinical effectiveness of immunotherapy with N-CWS . The subjects were stratified by a gross stage of cancer and degree of operative curability . They were then r and omly assigned to either chemotherapy group or chemotherapy plus immunotherapy group . Immunotherapy used was intradermal injection of 400 micrograms of N-CWS which was given weekly for the first month and monthly thereafter . After the specimen was examined microscopically , the patients were classified by histological stage of cancer and radicality of surgical intervention into curative or non-curative groups . The patients were surveyed for survival period in December 1981 . No statistical difference was found between the two treatment groups in age , sex or operative procedures that might influence the patient 's survival . As a result , statistical intergroup difference in survival rates was not seen in patients of the curative group , probably due to short observation period . However , the intergroup difference in survival rates was statistically significant in patients of the non-curative group ( p less than 0.01 ) . These results indicate that the immunotherapy with BCG-CWS or with N-CWS is effective in patients undergoing gastrectomy for gastric cancer A group of 243 patients with gastric cancer was subjected to a prospect i ve r and omized trial of adjuvant chemotherapy after curative gastrectomy . One of the three arms ( regimen A ) is induction therapy with a three-drug combination of mitomycin C ( MMC ) , 5-fluorouracil ( 5-FU ) , and cytosine arabinoside ( ara-C ) followed by intermittent oral administration of 5-FU for two years ( MFC + F ) . In regimen B , 5-FU in regimen A is replaced by ftorafur , administered on the same schedule as regimen A ( MF'C + F ' ) . Regimen C is the control , in which patients are treated by surgery alone . Regimen A was proven effective for the suppression of relapse in the limited groups of moderately locally advanced cancer ; five-year survival rates of the subset of stages I , II , and III were 72.1 % with regimen A and 53.1 % with regimen C ( P less than .05 ) . Regimen B yielded a better survival than the control , although the difference did not reach statistical significance . The results seem to favor 5-FU as adjuvant chemotherapy for gastric cancer In a multicenter trial the efficacy of intraperitoneal administration of cisplatin after radical or palliative resection of gastric carcinoma with respect to overall survival was investigated . In 64 r and omised patients , patients treated with intraperitoneal perfusion did not show a benefit in the overall survival after a median follow-up of 18 months The effect of postoperative immunochemotherapy with mitomycin C ( MMC ) , 5-fluorouracil ( 5-FU ) and OK-432 was evaluated as an adjuvant therapy after curative resection for gastric cancer . Immediately after surgery , patients were r and omly allocated to the following three treatments : ( A ) chemotherapy with MMC and 5-FU ( 32 cases ) ; ( B ) chemoimmunotherapy with MMC , 5-FU and OK-432 ( 33 cases ) ; and ( C ) surgery alone as control ( 34 cases ) . There were no significant differences in the background factors influencing survival time among the groups , and there was no dose-distribution of chemotherapeutic agents between groups A and B. While the differences were not statistically significant , the survival rate and disease-free interval of group B were better than those of groups A or C. Side effects such as gastroenteric disorder , leukopenia ( less than 3,000/mm3 ) , thrombocytopenia ( less than 7 X 10(4)/mm3 ) and increase of serum transaminase level ( GPT greater than or equal to 100 units ) were less frequently observed in group B than in group A. The results of the present study seemed to indicate that chemoimmunotherapy with OK-432 may be effective for surgical adjuvant therapy Following curative resection for gastric adenocarcinoma , 142 patients were r and omized to receive adjuvant chemotherapy of methyl‐CCNU and 5‐FU or to be  closely followed without chemotherapy . The median patient has been followed for four years . At the present time , there have been 38 recurrences and 40 deaths among the 71 patients in the control arm and 28 recurrences with 29 deaths in the group of patients r and omized to chemotherapy .  Median survival for control patients is 33 months whereas it is estimated to be in excess of four years for the adjuvant therapy group . A survival advantage appears to be associated with adjuvant treatment , a test for treatment difference being significant ( P < 0.03 ) after adjustment for important covariates . Survival and disease‐free intervals are longer in the chemotherapy arm for patients in all prospect i ve stratification subgroups ( proximal and total vs distal subtotal gastrectomy , presence or absence of lymph node metastases , invasion of adjacent organs vs confined to stomach wall and location of tumor within the stomach ) . A final assessment of this surgical adjuvant approach must await complete results of this trial , as well as of others currently in progress evaluating this same concept The aim of this trial was to investigate whether pre-operative chemotherapy leads to a 15 % higher curative resectability rate in patients with operable gastric cancer . In this r and omised trial , patients were allocated to receive either four courses of chemotherapy using 5-fluorouracil , doxorubicin and methotrexate ( FAMTX ) prior to surgery or to undergo surgery only .  Patients younger than 75 years of age with a good physical and mental condition and a histologically proven adenocarcinoma of the stomach without clinical or radiographic ( computed tomography scan ) evidence of distant metastases were eligible for this trial . Early gastric cancer or cardia carcinoma were excluded . The response to chemotherapy was evaluated after two and four courses . In case of progressive disease ( PD ) after two courses , patients were operated upon as soon as possible . Otherwise complete response ( CR ) partial response ( PR ) or stable disease ( SD ) , two more courses were scheduled . The st and ard surgical procedure was a limited lymphadenectomy ( D1 ) with staging biopsy of the para-aortic lymph nodes . Between September 1993 and February 1996 , 56 eligible and evaluable patients were entered : 27 were r and omised to receive FAMTX before surgery and 29 to undergo surgery only . In the FAMTX + surgery treatment group , 15/27 ( 56 % ) had curative resections versus 18/29 ( 62 % ) in the surgery only arm . There was no difference in the frequency of TNM stages I + II in both treatment arms : 15/27 versus 15/29 . Due to PD and /or toxicity , 12 patients ( 44 % ) could not complete the planned four courses of FAMTX . Response evaluation after chemotherapy was possible in 25 patients : 2 CR , 6 PR , 8 SD and 9 PD . The difference in curative resectability rate was 6.5 % ( 95 % confidence interval -32 to + 19 % ) in favour of surgery only . Downstaging for stages I + II did not occur . PD was more often the reason for not completing the planned four courses than toxicity . More active regimens than FAMTX are required for future r and omised trials A study group including 55 institutions in Japan evaluated the effect of adjuvant cyclophosphamide therapy on 461 patients who had undergone curative resection for stomach cancer . Patients , who were followed up for over three years , were r and omly divided into three groups : curative resection and long-term drug therapy ; curative resection and short-term drug therapy ; and curative resection and no drug therapy . Long-term therapy consisted of ( a ) twice-weekly intravenous doses of 500 mg of cyclophosphamide for four weeks and , after five weeks with no medication , ( b ) 100 mg/day , given orally , for 40 days and , after ten weeks with no medication , ( c ) 100 mg/day , given orally , for 40 days . Short-term therapy consisted of only the first course of therapy ( ie , twice-weekly intravenous doses of 500 mg for four weeks ) . The effect of cyclophosphamide  differed , depending on the patients ' levels of serosal and lymph node invasion : Short-term therapy was more effective in patients with lymph node involvement , and long-term therapy was more effective in patients with serosal involvement The overall survival in patients with gastric cancer is low , even among those undergoing resection . It has been hoped that the development of adjuvant therapy might improve survival in patients following surgery when tumour burden was minimal and both chemotherapy and radiotherapy have been proposed as suitable for use in gastric cancer . Their value has been evaluated by the British Stomach Cancer Group Second adjuvant therapy trial . 436 patients entered a prospect i ve , r and omised , controlled trial of adjuvant radiotherapy or cytotoxic chemotherapy with mitomycin , doxorubicin , and fluorouracil  after gastrectomy for adenocarcinoma . After at least 5 years , there have been 372 deaths of which 7 were due to surgical complications and 327 from recurrent cancer . Following stratified r and omisation , 145 patients were allocated to  surgery alone  , 153 to receive adjuvant radiotherapy , and 138 to adjuvant combination chemotherapy . The overall 2-year and 5-year survival were 33 % ( 95 % confidence interval 31 - 35 % ) and 17 % ( 13 - 21 % ) . No survival advantage has been shown for those patients receiving either adjuvant therapy compared to those undergoing surgery alone . The 5-year survival for surgery alone was 20 % , for surgery plus radiotherapy 12 % , and for surgery plus chemotherapy 19 % . Surgery , therefore , remains the st and ard treatment for this condition and the use of adjuvant treatments should be restricted to controlled trials A prospect i ve controlled study of combined chemotherapy with 5-fluorouracil , vinblastine and cyclophosphamide was conducted in 53 patients with radical resection for gastric carcinoma . The patients were divided into two groups , a  control group of 26 patients and a chemotherapy group of 27 patients , that were similar in regard to age , sex , location of carcinoma , type of resection and pathologic findings . No significant differences in survival rate were observed between the control group and the chemotherapy groups In order to evaluate the role of adjuvant IORT in the treatment of resectable gastric carcinoma , we carried out a r and omized trial comparing surgery and surgery+adjuvant IORT . The study included 115 patients within a 74-month period , 51 of them received a single application of 28 Gy to the celiac axis . Patients were comparable with regard to age , sex , tumor stage and operative morbidity . The difference in mean survival time  ( IORT : 26.9 months vs. non-IORT , 30.8 months ) and tumor-related death in the long-term course ( mean follow-up period 29.2 months ) with 29.4 % ( 15/51 ) in the IORT-treated patients vs. 31.2 % ( 20/64 ) in non-irradiated patients did not reach significance Three hundred fifteen patients with operable gastric cancer were r and omized to receive fluorouracil , Adriamycin ( doxorubicin ; Adria Laboratories , Columbus , OH ) , and mitomycin ( FAM ) or no adjuvant treatment between September 1981 and July 1984 . After excluding ineligible patients , 281 patients are included in this analysis . Treatment was moderately well tolerated by the majority of patients , the common side effects being nausea and vomiting ( 58 % ) and alopecia ( 57 % ) . Three possible treatment-related deaths were seen , all due to cardiac failure . At median follow-up of 68 months , 164 patients have died , 73 in the treated arm and 91 in the control arm . There was no significant difference in disease-free or overall survival between the two arms of the study ( P = 0.21 ) . There is some evidence that patients with more advanced carcinoma ( T3-T4 ) derived some benefit from treatment ( P = 0.04 ) . The interpretation of this finding must take into account that all subgroups were defined retrospectively , and this could , therefore , be a chance finding . We conclude that adjuvant chemotherapy as given in this trial is not indicated as routine treatment in operable gastric cancer , but that further evaluation in stage T3-T4 patients is warranted One hundred-three patients with a potentially curative operation of a histologically proven gastric cancer were r and omly assigned to a control and chemotherapy group after stratification according to tumor stage II and III . Chemotherapy courses with 5-fluorouracil ( 10 mg/kg/day ) and BCNU ( 40 mg/m2/day ) for 5 days were administered eight times in 6 - 8 week intervals . Age , sex , and tumor location were matched in the chemotherapy and control groups . Five patients declined treatment after r and omization . Three years after initiating the study , the tumor has recurred in 38 of the 103 patients . There were 21 recurrences of 54 controls and 14 recurrences of 44 patients who received chemotherapy , and 17 and ten deaths , respectively , due to tumor relapse . The results of our study to data show a high degree of statistical probability that adjuvant chemotherapy with the regime used has no influence on the recurrence-free interval and survival time in gastric cancer BACKGROUND / AIMS Gastric cancer remains a disease with a poor and dismal prognosis even after radical surgical resection . The present study attempts to clarify whether neo and adjuvant hypoxic upper abdominal chemotherapy can improve the survival of patients with gastric cancer undergoing radical surgical resection . Patterns of failure after surgery for gastric cancer include peritoneal seeding , resection margin recurrence , and liver metastasis . METHODOLOGY From October 1995 to February 1999 , 58 patients with resectable gastric cancer were r and omly assigned to three groups . Hypoxic upper abdominal chemotherapy was carried out using Mitomycin-C , 5-Fluorouracil , Leucovorin , and Farmorubicin , 10 days before surgery , and 20 days following surgery , in Group A ( n=20 ) with or without in Group B ( n=19 ) systemic chemotherapy ; the remaining patients ( Group C : n=19 ) had neither neo nor adjuvant treatment . RESULTS The 4-year survival of Group C patients was 29.2 % . Group A patients ( surgery plus hypoxic neo and adjuvant chemotherapy and systemic chemotherapy ) had a 4-year survival of 45.5 % versus a 4-year survival of 39.2 % of Group B patients ( surgery and hypoxic neo and adjuvant abdominal perfusion ) . Patients of all stages , histologically confirmed , were included in this study . CONCLUSIONS Patients suffering from gastric carcinoma have demonstrated statistically improved survival by combining resectional surgery with neo and adjuvant hypoxic upper abdominal perfusion and adjuvant systemic chemotherapy This study evaluated combined 5‐fluorouracil ( 5FU ) and doxorubicin as postoperative adjuvant chemotherapy for patients who had undergone potentially curative resection of a primary gastric adenocarcinoma . One hundred twenty‐five eligible and evaluable patients were stratified according to extent of surgical resection , location of the primary tumor within the stomach , and lymph node status . They were then r and omized to either receive three cycles of chemotherapy or be observed . The median time from patient entry was 7 years . Results showed no significant difference in time to recurrence . The 5‐year survival rate was 33 % for the observation arm and 32 % for the adjuvant therapy arm . The data excluded a 16 % improvement in the 5‐year survival rate for patients receiving chemotherapy with a P value less than 0.05 . There were two drug‐related fatalities due to sepsis . These results demonstrate no substantive benefit for this chemotherapy regimen as postoperative adjuvant treatment of resected gastric cancer PURPOSE The long-term survival probability of patients who undergo surgery for stage 3 and 4 gastric cancer is poor , predominantly due to metastatic spread of the tumor . Depending on the type of tumor histology , the pathway of metastases is mainly peritoneal or hepatic dissemination . Interruption of this mechanism may be possible by intraperitoneal chemotherapy ( IPT ) . PATIENTS AND METHODS In a prospect i ve r and omized trial of 67 patients undergoing surgery for stage 3 and 4 gastric cancer , 33 patients underwent adjuvant postoperative IPT with cisplatin , while 34 control subjects remained untreated .  RESULTS Patients in the treatment group received a median of four IPT perfusions . Apart from frequent nausea , no adverse reactions or complications were noted . The median disease-free survival duration s were 12.7 months and 9.7 months in treated patients and controls , respectively ( P = .8 ) . After a median follow-up duration of 72 months , 54 patients ( 80 % ) had died of primary disease or related complications . The median survival duration for IPT patients was 17.3 months as compared with 16.0 months for controls ( P = .6 ) . Autopsies were performed on 12 ( 18 % ) of 54 patients who died , and showed tumor spread to the peritoneal cavity and /or to the liver , irrespective of the application of IPT . CONCLUSION IPT with cisplatin monotherapy does not improve survival probability after surgery for stage 3 and 4 gastric cancer . The reasons for ineffectiveness of IPT may be the choice of an unsuitable chemotherapeutic agent , an inefficient modus of application , or a lack of sufficient drug penetration into the serosa or peritoneal metastasis Background . Continuous hyperthermic peritoneal perfusion ( CHPP ) with a solution that contained 10 μg/ml mitomycin C was devised initially as a method for intraperitoneal thermochemotherapy . The authors conducted a r and omized clinical trial to evaluate the efficacy of  CHPP  as a prophylactic treatment for prevention of peritoneal recurrence of gastric cancer with serosal invasion A group of 496 cases was used in a controlled trial to study the possible value of mitomycin C as an adjuvant to curative surgery for gastric cancer . Patients assigned to receive the drug were given mitomycin C , 0.8 mg/kg body weight intravenously , twice a week for 5 weeks immediately after surgery . The control group was treated with surgery alone .  Sixty-six patients were excluded from the study because of non-curative surgery . There was no over-all difference in survival and cancer death rates at 5 and 10 years between treated and control groups . However , a survival rate 18.6 % higher at 5 years was observed in the subset of patients who had moderately advanced lymphatic metastases , and a survival rate 26.4 % higher at 5 years was observed in the subset of patients who had involved serosa . The difference in cancer death rate was 14.5 and 24.0 % in each subset , respectively . These significant differences persisted at 10 years . The effect of chemotherapy seemed to result from the successful inhibition of peritoneal dissemination and local recurrence . An adverse effect was observed in patients in the early stages cancer . These results suggest that mitomycin C could be useful as an adjuvant to curative surgery for moderately advanced stages of gastric cancer The results of a prospect i ve r and omized trial of adjuvant treatment after curative resection for gastric cancer are reported . The study consisted of three arms : ( 1 ) surgery only ; ( 2 ) chemotherapy ( 5‐fluoro‐uracil ( FU ) and 1‐(2‐chloroethyl)‐3‐(4‐methylcyclohexil)‐1‐nitrosourea ( Me‐CCNU ) ) after surgery ; ( 3 ) chemo‐immunotherapy ( FU , Me‐CCNU and levamisole ) after surgery .  Between March 1977 and June 1981 , 235 patients were included in the study by 18 co‐operating institutions . Thirteen per cent of patients in arm 2 and thirteen per cent in arm 3 suffered major toxicity , necessitating interruption of treatment . Two of these patients died of marrow aplasia . Statistical analysis of survival showed that prognosis was influenced by the well‐known prognostic variables , invasion of the wall , nodal status and site of tumour . The different treatments in the three arms , however , did not show any impact on prognosis , even when adjustments were made for the most relevant prognostic variables . Given the lack of effect on survival and the presence of clinical ly important toxicity , FU and Me‐CCNU ± levamisole can not be recommended as adjuvant therapy for resected gastric cancer BACKGROUND To study the survival benefit of adjuvant chemotherapy in gastric cancer , seven cancer centres in Japan carried out a phase III clinical trial of adjuvant chemotherapy after curative gastrectomy for macroscopically serosa-negative gastric cancer . METHODS 579 patients were enrolled in the study , stratified by disease stage ( T1 , n=188 ; T2 , n=323 ) , and allocated r and omly adjuvant chemotherapy or no further treatment .  285 of 288 cases in the treatment group and 288 of 291 in the control group were eligible . Six cases were excluded because they did not fulfill the entry criteria . The treatment group had intravenous mitomycin ( 1.4 mg/m2 ) and fluorouracil ( 166.7 mg/m2 ) twice weekly for 3 weeks after surgery , and oral UFT ( uracil plus tegafur , 300 mg daily ) for 18 months . Analyses were by intention to treat . FINDINGS No serious toxic effects were observed in the treatment group . At median follow-up of 72 months , 59 patients in the control group and 47 in the treatment group had died . There was no significant difference in survival between the groups ( 5-year survival 82.9 % control vs 85.8 % treated ; hazard ratio 0.738 [ 95 % CI 0.498 - 1.093 ] ) . 5-year survival of patients with T1 ( mucosal or submucosal ) cancer in the control and treatment groups was 94.9 % versus 92.0 % , and that of patients with T2 ( muscularis propria or subserosa ) cancer was 76.9 % versus 83.0 % . However , a test for heterogeneity and interaction over T1 and T2 subgroups revealed no significant difference in terms of drug response . INTERPRETATION There was no survival benefit with this adjuvant therapy regimen for patients with macroscopically serosa-negative gastric cancer ( T1 and T2 ) after curative gastrectomy . Patients with T1 cancer can be excluded from future trials , because curative surgery alone yielded a very good survival rate and there seemed no need for adjuvant therapy As a result of their previous experience with mitomycin C at high discontinuous doses in advanced gastric cancer , the authors studied its role as an adjuvant for locally advanced cases after surgical complete resection . Results from 70 evaluable patients are presented . Patients were allocated r and omly to receive mitomycin C , 20 mg/m2 I.V. direct once every 6 weeks , four courses , or a placebo . After a follow-up period of 250 weeks , seven patients of treatment arm and 23 controls have already relapsed ( p < 0.001 ) . Toxicity was moderate and controllable by symptomatic measures . The authors consider this investigation a positive contribution in the field of adjuvant therapy of gastric cancer A cooperative study on surgical adjuvant immunochemotherapy for prevention of postoperative recurrence of gastric cancer was carried out by Kondo 's group from July 1974 to December 1977 . A total of 848 patients with gastric cancer underwent curative resection were eligible . Of 848 patients , 819 cases with complete description of patient 's background were evaluable : Group A ( surgery + MMC + 5-FU : chemotherapy ) 253 cases , group B ( surgery + MMC + 5-FU + OK-432 or PSK : immunochemotherapy ) 282 and group C ( surgery alone ) 284 . The 5-year corrected survival rates of total cases using Cox 's proportional hazard model were 76.2 % with group A , 73.6 % with group B and 73.3 % with group C. And the 10-year survival rates were 67.6 % with group A , 64.3 % with group B and 63.9 % with group C. The difference in survival rate among groups A , B and C was not statistically significant . In the evaluation of prognostic factors by Cox 's proportional hazard model , level of curative resection , extent of resection , histological stage and Kajitani 's classification had an influence upon survival rates , in which degrees of metastasis in lymph node and serous infiltration were also involved . The significance of postoperative adjuvant immunochemotherapy has not been clarified PURPOSE In a r and omized clinical trial ( European Organization for the Research and Treatment of Cancer [ EORTC ] no. 40813 ) on adjuvant chemotherapy in gastric cancer , results obtained after administration of the FAM2 regimen ( fluorouracil [ 5-FU ] , doxorubicin , and mitomycin ) were compared with results obtained after surgery alone to assess the effect of this regimen on overall survival , time to progression , and disease-free interval . PATIENTS AND METHODS Three hundred fourteen patients who had undergone curative resection for stage II or stage III ( International Union Against Cancer [ UICC ] 1978 ) gastric adenocarcinoma were r and omized to receive chemotherapy ( treatment arm ) or no further treatment ( control arm ) . The chemotherapy schedule was repeated every 43 days for seven cycles . The log-rank test and the Cox model were used for statistical analysis . RESULTS Of 314 patients , 159 comprised the control group and 155 the FAM2 group . Nineteen FAM2 patients never received chemotherapy . The median number of cycles was five . Of the patients started on adjuvant treatment , severe hematologic and nonhematologic toxicity ( grade s 3 or 4 , World Health Organization [ WHO ] scale ) occurred , respectively , in 6 % to 9 % and in 1 % to 29 % of cases . The overall 5-year survival rate was 70 % for stage II and 32 % for stage III patients . No statistically significant difference was found between overall survival of the two treatment arms ( P = .295 ) . However , time to progression was significantly delayed in the FAM2 arm ( P = .020 ) and disease-free survival showed borderline significance ( P = .068 ) . CONCLUSION FAM2 , in view of its high toxicity , can not be advocated as st and ard adjuvant treatment for gastric cancer . Large-scale clinical trials using more active , less toxic regimens are required to demonstrate whether adjuvant chemotherapy provides any real benefit PURPOSE The efficacy of adjuvant chemotherapy in gastric cancer is controversial . We conducted a phase III , r and omized , multicentric clinical trial with the goal of assessing the efficacy of the combination of mitomycin plus tegafur in prolonging the disease-free survival and overall survival of patients with resected stage III gastric cancer . PATIENTS AND METHODS Patients with resected stage III gastric adenocarcinoma were r and omly assigned , using sealed envelopes , to receive either chemotherapy or no further treatment . Chemotherapy was started within 28 days after surgery according to the following schedule : mitomycin 20 mg/m(2 ) intravenously ( bolus ) at day 1 of chemotherapy ; 30 days later , oral tegafur at 400 mg bid daily for 3 months . Disease-free survival and overall survival were estimated using the Kaplan-Meier analysis and the Cox proportional hazards model . RESULTS Between January 1988 and September 1994 , 148 patients from 10 hospitals in Catalonia , Spain , were included in the study . The median follow-up period was 37 months . The tolerability of the treatment was excellent . The overall survival and disease-free survival were higher in the group of patients treated with chemotherapy ( P = .04 for survival and P = .01 for disease-free survival in the log-rank test ) . The overall 5-year survival rate and the 5-year disease-free survival rate were , respectively , 56 % and 51 % in the treatment group and 36 % and 31 % in the control group . CONCLUSION Our positive results are consistent with the results of recent studies ; which conclude that there is a potential benefit from adjuvant chemotherapy in resected gastric cancer 411 patients were entered into a prospect i ve , r and omised controlled trial of adjuvant chemotherapy after gastrectomy for adenocarcinoma . After a follow-up of at least 5 1/2 years there has been no survival advantage for those receiving adjuvant 5-fluorouracil and mitomycin C with or without an induction course of 5-fluorouracil , vincristine , cyclophosphamide , and methotrexate compared with those undergoing surgery only . There have been 366  deaths , including 22 from treatment-related conditions . A multivariate analysis of prognostic factors demonstrated that stage of disease , nodal and resection margin involvement , and the presence of residual disease are significant determinants of survival . Weight loss before surgery had a significant independent influence on survival . The combination of preoperative symptoms and intraoperative findings may be used to select patients for radical or palliative procedures Attempts to prevent peritoneal carcinomatosis after surgery for gastric cancer by intraperitoneal administration of anticancer drugs have not been successful , largely because the drugs are not retained in the peritoneal cavity . We have assessed the prophylactic efficacy of a delayed-release preparation -- mitomycin adsorbed onto activated charcoal ( M-CH ) . 50 patients with gastric cancer and serosal infiltration were r and omly assigned intraperitoneal treatment with M-CH ( 50 mg mitomycin intraoperatively ) or no anticancer prophylaxis ( control ) . Survival rates for the 3 years of follow-up were significantly higher among the 24 M-CH recipients ( 1 was lost to follow-up ) than among the 25 controls ( p less than 0.01 ) . There were significant differences in survival between the groups at 1.5 years after r and omisation ( difference 34.6 % [ 95 % confidence interval 8.5 - 60.8 % ] ; p less than 0.01 ) and at 2.0 , 2.5 , and 3.0 years ( 41.7 % [ 14.2 - 69.1 % ] ; p less than 0.005 ) . The concentration of mitomycin was significantly higher in peritoneal exu date than in plasma for 24 h after drug administration . Side-effects were slight and well tolerated . Thus , peroperative intraperitoneal treatment with M-CH seems to improve survival after gastrectomy for gastric cancer , presumably by a prophylactic effect on peritoneal recurrence BACKGROUND The extent to which chemotherapy may relieve tumour-related symptoms , improve quality of life and prolong survival in patients with gastric cancer is not known in spite of the extensive use of this treatment modality . The aim of this study was to estimate any gain in the quantity and quality of life produced by chemotherapy in these patients . PATIENTS AND METHODS Between January 1991 and February 1995 , 61 patients with gastric cancer were r and omized to either chemotherapy in addition to best supportive care or to best supportive care . Chemotherapy was allowed in the latter group if the supportive measures did not lead to palliation . Chemotherapy was the ELF-regimen consisting of 5-fluorouracil , leucovorin and etoposide , or , in elderly patients with poor performance , a 5-fluorouracil/leucovorin regimen ( FLv ) .  Quality of life was evaluated with the EORTC-QLQ-C30 instrument . RESULTS More patients in the chemotherapy group ( 45 % , 14/31 ) had an improved or prolonged high quality of life for a minimum period of 4 months compared to those in the best supportive care group ( 20 % , 6/30 , P < 0.05 ) . A similar difference was seen in the treating physician 's evaluation of whether the patient was subjectively improved or continued to do well for at least 4 months ( 17/31 , 55 % versus 6/30 , 20 % , P < 0.01 ) . Overall survival was longer in the chemotherapy group ( median 8 vs. 5 months ) although the difference was not statistically significant ( P = 0.12 ) . After corrections for imbalances in pretreatment characteristics , chemotherapy treatment was , however , associated with a survival benefit ( P = 0.003 ) . Also , the quality -adjusted survival time and time to disease progression were longer for patients r and omized to chemotherapy ( median 5 vs. 2 months , P = 0.03 ) . CONCLUSIONS The results show that chemotherapy can add to both quantity and quality of life in advanced gastric cancer . The number of patients who benefit from treatment is , however , still rather limited
target: Furthermore , this therapy could increase the dem and on radiation re sources .
  There is no evidence on which to make a recommendation for patients with node-negative tumours that have not penetrated the muscularis propria .
  For patients unable to undergo radiation , adjuvant chemotherapy alone may be of benefit , particularly for those with lymph-node metastases .
  There is insufficient evidence from r and omized trials to recommend neoadjuvant chemotherapy , or neoadjuvant or adjuvant radiotherapy or immunotherapy , either alone or in combination , outside a clinical trial .
background: OBJECTIVE To make recommendations on the use of neoadjuvant or adjuvant therapy in addition to surgery in patients with resectable gastric cancer ( T1 - 4 , N1 - 2 , M0 ) .
  OPTIONS Neoadjuvant or adjuvant treatments compared with " curative " surgery alone .
  OUTCOMES Overall survival , disease-free survival , and adverse effects .
  The radiation fields used can possibly damage the left kidney , result ing in hypertension and other renal problems .