A randomized trial comparing adjuvant fluorouracil, epirubicin, and mitomycin with no treatment in operable gastric cancer. Efficiency of adjuvant immunochemotherapy following curative resection in patients with locally advanced gastric cancer [Adjuvant chemotherapy in patients with radical resection of stomach cancer: 5-year results of a prospective randomized study]. Multicentre randomised study of adjuvant chemotherapy with mitomycin C and tegafur or tegafur-uracil in gastric cancer. Adjuvant chemotherapy with 5-fluorouracil and cisplatin compared with surgery alone for gastric cancer: 7-year results of the FFCD randomized phase III trial (8801). Surgical treatment variation in a prospective, randomized trial of chemoradiotherapy in gastric cancer: The effect of undertreatment Randomized crossover trial of intravenous 5-FU versus oral UFT both modulated by leucovorin: a one-centre experience. Postoperative adjuvant 5‐fluorouracil plus methyl‐CCNU therapy for gastric cancer patients. Eastern cooperative oncology group study (EST 3275) Differences in toxicity across gender in patients treated with chemoradiation for rectal cancer. Long term (five-year) survival following radical surgical treatment plus adjuvant chemotherapy (FAM) in advanced gastric cancer: a controlled study. Weekly 5-fluorouracil and leucovorin: achieving lower toxicity with higher dose-intensity in adjuvant chemotherapy after colorectal cancer resection. Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1,864 patients. Evaluation of adjuvant UFT for gastric cancer. A controlled, prospective, randomised trial of adjuvant chemotherapy or radiotherapy in resectable gastric cancer: interim report. British Stomach Cancer Group. 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 immunochemotherapy combined with OK-432 following surgery of stomach cancer]. The effect of adjuvant chemotherapy in gastric carcinoma is dependent on tumor histology: 5-year results of a prospective randomized trial. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. 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 Randomized trial of adjuvant chemotherapy with mitomycin, Fluorouracil, and Cytosine arabinoside followed by oral Fluorouracil in serosa-negative gastric cancer: Japan Clinical Oncology Group 9206-1. A phase i study of bolus 5-fluorouracil and leucovorin combined with weekly paclitaxel (FLTAX) as first-line therapy for advanced gastric cancer. [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 [Efficacy of intraoperative hypotonic peritoneal chemo-hyperthermia combined with early postoperative intraperitoneal chemotherapy on gastric cancer]. Randomized trial of adjuvant chemotherapy after curative resection for gastric cancer. Prognostic factors in resectable gastric cancer: Results of EORTC study no. 40813 on FAM adjuvant chemotherapy Randomized trial of adjuvant chemotherapy versus control after curative resection for gastric cancer: 5-year follow-up Adjuvant 5‐fluorouracil plus doxorubicin in D2‐3 resected gastric carcinoma Second-line treatment with oxaliplatin, leucovorin and 5-fluorouracil in gemcitabine-pretreated advanced pancreatic cancer: A phase II study A phase II and pharmacologic study of fluorouracil given by a 1-hour infusion daily for 5 days with leucovorin and interferon alpha-2a in adenocarcinoma of the large bowel. Gastric carcinoma treated by chemotherapy after resection: a controlled study. A combination chemotherapy of 5-fluorouracil and cisplatin against advanced gastric cancer. A randomised phase III trial of adjuvant radio-chemotherapy comparing Irinotecan, 5FU and Leucovorin to 5FU and Leucovorin in patients with rectal cancer: a Hellenic Cooperative Oncology Group Study. Gemcitabine, 5‐fluorouracil, and leucovorin in advanced biliary tract and gallbladder carcinoma A prospective, randomized evaluation of intensive‐course 5‐fluorouracil plus doxorubicin as surgical adjuvant chemotherapy for resected gastric cancer Results of surgery on 6589 gastric cancer patients and immunochemosurgery as the best treatment of advanced gastric cancer. Phase I/II study of oxaliplatin with weekly bolus fluorouracil and high-dose leucovorin (ROX) as first-line therapy for patients with colorectal cancer. Adjuvant mitomycin and fluorouracil followed by oral uracil plus tegafur in serosa-negative gastric cancer: a randomised trial Final results of a phase III clinical trial of adjuvant chemotherapy with the modified fluorouracil, doxorubicin, and mitomycin regimen in resectable gastric cancer. ADJUVANT CHEMOTHERAPY IN OPERABLE GASTRIC CANCER: 5 Year Follow-up of First British Stomach Cancer Group Trial
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 Background Despite curative resection , 50%–90 % of gastric cancer patients die of disease relapse . Although some clinical trials have indicated that chemotherapy and immunochemotherapy may be effective modalities , more recent studies have not been able to define the st and ard treatment for advanced gastric cancer . The present study evaluated the effect of adjuvant immunochemotherapy with the use of BCG ( bacille Calmette-Guérin ) and FAM ( 5-fluorouracil , adriamycin , mitomycin C ) chemotherapy on the survival of  patients with locally advanced resectable gastric cancer . Methods A total of 156 patients with stage III or IV gastric cancer who had undergone curative resection were r and omly assigned to three treatment groups : BCG + FAM ( immunochemotherapy ) , FAM ( chemotherapy ) , and control ( surgery only ) . Treatment was continued for 2 years or until death . Further postsurgical follow up was carried on for up to 10 years . Results Overall 10-year survival was 47.1 % for the immunochemotherapy group ( P < 0.037 vs FAM and P < 0.0006 vs control ) , 30 % for the chemotherapy group ( vs control , NS ) , and 15.2 % for the control group . In patients with pT2/T3 primary tumors , 10-year survival was 55.3 % for BCG + FAM vs 28.2 % for FAM ( P < 0.01 ) and 14.6 % for the control group ( P < 0.00018 ) . BCG + FAM signifi-cantly improved the survival of patients with intestinal-type but not diffuse-type cancer . Immunochemotherapy was well tolerated . Conclusion This study , based on a limited number of patients , indicates that adjuvant immunochemotherapy ( BCG + FAM ) may prolong the survival of gastric cancer patients after curative gastrectomy ; in particular , in patients with pT2/T3 tumors and intestinal-type primary tumors . There was no survival benefit from FAM adjuvant chemotherapy 102 patients with operable gastric carcinoma were r and omly allocated to untreated control , polychemotherapy , chemoimmunotherapy . At a median follow-up of 5 years , chemotherapy did not improve the overall survival rate . However , in certain subgroups , patients with lymphnode metastases and intestinal tumor type showed a significant survival benefit when treated with adjuvant chemotherapy . Furthermore , we found the site of first recurrence very closely related to the type of tumor histology . Regardless of the positive effect of chemotherapy in retrospective subset- analysis , we do not generally recommend the use of polychemotherapy in operable gastric carcinoma OBJECTIVE To compare therapeutic results and five year survival after two regimens of adjuvant chemotherapy after resections for gastric cancer . DESIGN Prospect i ve r and omised multicentre trial . SETTING S 21 departments of surgery . SUBJECTS 243 patients with stage II , III , or IV gastric cancer . INTERVENTIONS All patients received an intravenous bolus of mitomycin C 20 mg on the day of operation , and 10 mg on the first postoperative day . They were then r and omised to receive either tegafur 600 mg or tegafur-uracil 600 mg orally daily beginning two weeks after operation and continuing for two years . Patients with histological confirmed stage IV disease also received mitomycin C 10 mg every three months starting one month after operation . MAIN OUTCOME MEASURES Survival and side effects . RESULTS 13 patients ( 5 % ) were withdrawn from the study , leaving 230 for analysis . There were no serious side effects and both drugs were safe when given continuously for two years . There were no significant differences in 5 year survival ( though patients who were given tegafur-uracil tended to live longer ) , except when patients who had histological curative resections were compared with and those with poorly differentiated adenocarcinoma ( p = 0.04 ) BACKGROUND The aim of this study was to evaluate the efficacy of adjuvant chemotherapy after resection for gastric cancer in a r and omized controlled trial . PATIENTS AND METHODS After curative resection , stage II-III-IVM0 gastric cancer patients were r and omly assigned to postoperative chemotherapy or surgery alone . 5-Fluorouracil ( 5-FU ) 800 mg/m(2 ) daily ( 5-day continuous infusion ) was initiated before day 14 after resection . One month later , four 5-day cycles of 5-FU ( 1 g/m(2 ) per day ) plus cisplatin ( 100 mg/m(2 ) on day 2 ) were administered every 4 weeks . RESULTS The study was closed prematurely after enrollment of 260 patients ( 79.7 % N+ ) , owing to poor accrual . At 97.8 months median follow-up , 5- and 7-year overall survival were 41.9 % and 34.9 % in the control group versus 46.6 % and 44.6 % in the chemotherapy group ( P=0.22 ) . Cox model hazard ratios were 0.74 [ 95 % confidence interval ( CI ) 0.54 - 1.02 ; P=0.063 ] for death and 0.70 ( 95 % CI 0.51 - 0.97 ; P=0.032 ) for recurrence . An invaded/removed lymph nodes ratio > 0.3 was the main independent poor prognostic factor identified by multivariate analysis ( P=0.0001 ) . Because of toxicity , only 48.8 % of patients received more than 80 % of the planned dose . CONCLUSION There was no statistically significant survival benefit with this toxic cisplatin-based adjuvant chemotherapy , but a risk reduction in recurrence was observed Background Intergroup 0116 ( Southwest Oncology Group 9008 ) , a national , multicenter , two-armed , prospect i ve , r and omized trial of adjuvant postoperative chemoradiotherapy , has demonstrated significant benefit . Methods We prospect ively captured complete surgical information , including the treatment of various lymph node stations , for 553 of the 556 eligible participants in this trial . Before any survival analysis , we coded D level by using the Japanese general rules and used the Maruyama program to estimate the likelihood of disease in undissected regional node stations , defining the sum of these estimates as the Maruyama Index of Unresected Disease ( MI ) . We analyzed survival with Cox multivariate regression  . Results Fifty-four percent of participating patients underwent D0 lymphadenectomy . The median MI was 70 ( range , 0–429 ) . In contrast to D level , MI proved to be an independent prognostic factor , even with adjustment for the potentially linked variables of T stage and number of positive nodes . We detected no significant interaction between surgical or pathologic variables and the favorable effect of adjuvant treatment , but the power to detect such interaction was generally low . Conclusions MI , a measure of unresected regional nodal disease in gastric cancer , proved an independent predictor of survival . Surgical undertreatment , as observed in this trial , clearly undermined survival Although intravenous ( IV ) 5-fluorouracil ( 5-FU ) and uracil/futraful ( UFT ) have comparable antitumour efficacy in the treatment of metastatic colorectal cancer ( MCC ) , we wanted to assess which of these two regimens would be preferred by our patients . We r and omized 20 previously untreated patients with MCC at our centre to receive oral UFT or bolus IV 5-FU both associated with leucovorin . After the first cycle patients were crossed over to the other arm . Before the third cycle we left patients to choose one of the regimens to continue their treatment until disease progression . Two patients chose 5-FU and 18 chose UFT ( P < 0.001 ) . Fewer side effects ( 50 % ) and convenience of home treatment ( 40 % ) were the main reasons for their choice for the oral regimen . UFT induced less mucositis ( P = 0 . 02 ) and diarrhoea ( P = 0 . 01 ) . We conclude that convenience and lower toxicity may explain the observed preference for oral UFT 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 The primary objective was to prospect ively investigate the efficacy and toxicity of bolus 5-fluorouracil ( 5-FU ) chemotherapy compared with the infusional 5-FU in combination with preoperative radiation in patients with locally advanced rectal cancer . Furthermore , in light of previous reports , toxicity profiles between men and women were also compared . Eighty-four consecutive patients with rectal adenocarcinoma were prospect ively treated . There were no differences in tumour response , local recurrence or survival between bolus versus infusional groups or gender groups . In locally advanced rectal cancer , preoperative infusional chemotherapy combined with radiation was found to be less toxic than bolus chemotherapy and radiotherapy . Both regimens produced more toxic effects in women compared with men Several drugs and their associations are being used for adjuvant or complementary chemotherapy with the aim of improving results of gastric cancer treatment . The objective of this study was to verify the impact of these drugs on nutrition and on survival rate after radical treatment of 53 patients with gastric cancer in stage III of the TNM classification . A control group including 28 patients who had only undergone radical resection was compared to a group of 25 patients who underwent the same operative technique followed by adjuvant polychemotherapy with FAM ( 5-fluorouracil , Adriamycin , and mitomycin C ) . In this latter group , chemotherapy toxicity in relation to hepatic , renal , cardiologic , neurological , hematologic , gastrointestinal , and dermatological functions was also studied . There was no significant difference on admission between both groups in relation to gender , race , macroscopic tumoral type of tumor according to the Borrmann classification , location of the tumor in the stomach , length of the gastric resection , or response to cutaneous tests on delayed sensitivity . Chemotherapy was started on average , 2.3 months following surgical treatment . Clinical and laboratory follow-up of all patients continued for 5 years . The following conclusions were reached : 1 ) The nutritional status and incidence of gastrointestinal manifestation were similar in both groups ; 2 ) There was no occurrence of cardiac , renal , neurological , or hepatic toxicity or death due to the chemotherapeutic method per se ; 3 ) Dermatological alterations and hematological toxicity occurred exclusively in patients who underwent polychemotherapy ; 4 ) There was no significant difference between the rate and site of tumoral recurrence , the disease-free interval , or the survival rate of both study groups ; 5 ) Therefore , we concluded , after a 5-year follow-up , chemotherapy with the FAM regimen did not increase the survival rate BACKGROUND Current st and ard therapy following resection of high-risk colon cancer is intravenous bolus 5-fluorouracil ( 5-FU ) with leucovorin ( LV ) , but there is no consensus on the optimum regimen of these drugs : practice ranges from the high toxicity Mayo Clinic schedule to the very low toxicity weekly QUASAR schedule . We present data for a weekly schedule that aims to provide moderately dose-intense treatment with low toxicity . PATIENTS AND METHODS One hundred and sixty-two patients were studied : 60 % male ; median age 65 years ( 36 % over 70 years ) ; 94 % colorectal primary . Treatment was intravenous bolus ( 5 min ) 5-FU 425 mg/m(2 ) plus D , L-LV 45 mg flat rate once weekly , for a planned 24 weeks . Data for toxicity , dose-reductions , delays and stoppages were collected . RESULTS Overall , 20 % of patients experienced any grade > or = 3 toxicity , most commonly diarrhoea ( 14 % patients ) . Dose reductions were made in 35 % of patients ( although only 21 % required 20 % or more reduction ) ; toxicity contributed to a decision to stop treatment before 24 weeks in 16 % of patients . Median delivered dose intensity ( DI ) was 96 % of planned ( 407 mg/m(2)/week ) during treatment , and 91 % of planned ( 385 mg/m(2)/week ) over the full 24 week treatment plan . Female sex and age > 70 years were significantly associated with higher rates of toxicity and dose adjustment , and lower delivered DI . CONCLUSIONS Weekly treatment at these doses is convenient and well-tolerated for the large majority of patients , and achieves DI comparable with the 5 days a month QUASAR schedule and other more toxic st and ard regimens PURPOSE To report the results of a planned safety analysis from a phase III trial comparing capecitabine plus oxaliplatin ( XELOX ) with bolus fluorouracil/leucovorin ( FU/LV ) as adjuvant therapy for stage III colon cancer . PATIENTS AND METHODS Patients with stage III colon carcinoma were r and omly assigned to receive either XELOX ( intravenous oxaliplatin plus oral capecitabine ; 3-week cycle for eight cycles ) or st and ard intravenous bolus FU/LV administered as the Mayo Clinic ( Mayo ; Rochester , MN ) or Roswell Park ( RP ; Buffalo , NY ) regimen for a similar length of time . A total of 1,886 patients were r and omly assigned . RESULTS The safety population comprised 1,864 patients , of whom 938 received XELOX and 926 received FU/LV . Most treatment-related adverse events ( AEs ) occurred at similar rates in both treatment arms . However , patients receiving XELOX experienced less all- grade diarrhea , alopecia , and more neurosensory toxicity , vomiting , and h and -foot syndrome than those patients receiving FU/LV . Compared with Mayo , XELOX showed fewer grade 3/4 hematologic AE and more grade 3/4 gastrointestinal AE . Compared with RP , XELOX showed less grade 3/4 gastrointestinal AE and more grade 3/4 hematologic AE . As expected grade 3/4 neurosensory toxicity and grade 3 h and -foot syndrome were higher with XELOX . Treatment-related mortality within 28 days from the last study dose was 0.6 % in the XELOX group and 0.6 % in the FU/LV group . CONCLUSION XELOX has a manageable tolerability profile in the adjuvant setting . Efficacy data will be available within the next 24 months In a trial of adjuvant chemotherapy with mitomycin and 5-FU followed by oral UFT for T1 and T2 gastric cancer after curative gastrectomy , there was no significant difference in survival between the treated and control ( surgery alone ) groups ( 5-year survival rate , 82.9 % control vs 85.8 % treated ) . Although not significantly different , 5-year survival for patients with T2 cancer was slightly higher in the treated group than in the control group ( 76.9 % control vs 83.0 % treated ) . This finding suggests that T2 cancer should remain the target of further trials of adjuvant chemotherapy A prospect i ve , r and omised controlled trial of surgery , surgery with adjuvant radiotherapy and surgery with adjuvant chemotherapy ( 5-fluorouracil , adriamycin and mitomycin C ) in operable gastric cancer is described . Four hundred and thirty-six patients were r and omly allocated to one of three treatment groups . With 12 months ' minimum follow-up , 334 patients have died , 292 from recurrent cancer . The median survival for all patients was 15 months . Neither form of adjuvant therapy provides any survival advantage . Surgery remains the principal treatment for operable gastric cancer . Care should be taken to st and ardise surgical treatment and any adjuvant treatments must be compared within the confines of controlled , r and omised trials 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 Postoperative immunochemotherapy with mitomycin C ( MMC ) , 5-fluorouracil ( 5-FU ) and OK-432 was evaluated as adjuvant therapy for curative resection in the cases of gastric cancer . One hundred and twenty-two patients ( 28 were excluded ) were r and omly assigned to 3 groups : Group A-MMC and 5-FU ( 28 cases ) ; Group B-MMC , 5-FU and OK-432 ( 33 cases ) ; Group C-control ( 33 cases ) . There were no differences in the back ground factors influencing survival time among each group . Group B showed better results in survival rate and disease free interval as compared with Group A or C. Minor and reversible side effects such as enterogastric disorder , leukopenia ( less than 3000/mm3 ) , thrombo cytopenia ( less than 7 X 10(4)/mm3 ) and elevation of serum transaminase ( S-GPT greater than or equal to 100 unit ) were equivalently observed in frequency in each Group A and B , but they were milder in Group B than Group 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 This phase III clinical trial evaluated the impact on disease-free survival ( DFS ) of adding oxaliplatin to bolus weekly fluorouracil ( FU ) combined with leucovorin as surgical adjuvant therapy for stage II and III colon cancer . PATIENTS AND METHODS Patients who had undergone a potentially curative resection were r and omly assigned to either FU 500 mg/m2 intravenous ( IV ) bolus weekly for 6 weeks plus leucovorin 500 mg/m2 IV weekly for 6 weeks during each 8-week cycle for three cycles ( FULV ) , or the same FULV regimen with oxaliplatin 85 mg/m2 IV administered on weeks 1 , 3 , and 5 of each 8-week cycle for three cycles ( FLOX ) . RESULTS A total of 2,407 patients ( 96.6 % ) of the 2,492 patients r and omly assigned were eligible . Median follow-up for patients still alive is 42.5 months . The hazard ratio ( FLOX v FULV ) is 0.80 ( 95 % CI , 0.69 to 0.93 ) , a 20 % risk reduction in favor of FLOX ( P < .004 ) . The 3- and 4-year disease-free survival ( DFS ) rates were 71.8 % and 67.0 % for FULV and 76.1 % and 73.2 % for FLOX , respectively . Grade 3 neurosensory toxicity was noted in 8.2 % of patients receiving FLOX and in 0.7 % of those receiving FULV ( P < .001 ) . Hospitalization for diarrhea associated with bowel wall thickening occurred in 5.5 % of the patients receiving FLOX and in 3.0 % of the patients receiving FULV ( P < .01 ) . A total of 1.2 % of patients died as a result of any cause within 60 days of receiving chemotherapy , with no significant difference between regimens . CONCLUSION The addition of oxaliplatin to weekly FULV significantly improved DFS in patients with stage II and III colon cancer .  FLOX can be recommended as an effective option in clinical practice 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 PURPOSE To evaluate the survival benefit of adjuvant chemotherapy after curative resection in serosa-negative gastric cancer patients ( excluding patients who were T1N0 ) , we conducted a multicenter phase III clinical trial in which 13 cancer centers in Japan participated . PATIENTS AND METHODS From January 1993 to December 1994 , 252 patients were enrolled into the study and allocated r and omly to adjuvant chemotherapy or surgery alone . The chemotherapy comprised intravenous mitomycin 1.33 mg/m2 , fluorouracil ( FU ) 166.7 mg/m2 , and cytarabine 13.3 mg/m2 twice weekly for the first 3 weeks after surgery , and oral FU 134 mg/m2 daily for the next 18 months for a total dose of 67 g/m2 . The primary end point was relapse-free survival . Overall survival and the site of recurrence were secondary end points . RESULTS Ninety-eight percent of patients underwent gastrectomy with D2 or greater lymph node dissection . There were no treatment-related deaths and few serious adverse events . There was no significant difference in relapse-free and overall survival between the arms ( 5-year relapse-free survival 88.8 % chemotherapy v 83.7 % surgery alone ; P = .14 and 5-year survival 91.2 % chemotherapy v 86.1 % surgery alone ; P = .13 , respectively ) . Nine patients ( 7.1 % ) in the chemotherapy arm and 17 patients ( 13.8 % ) in the surgery-alone arm had cancer recurrence . CONCLUSION There was no statistically significant relapse-free or overall survival benefit with this adjuvant chemotherapy for patients with macroscopically serosa-negative gastric cancer after curative resection , and there was no statistical difference between the two arms relating to the types of cancer recurrence . We do not recommend adjuvant chemotherapy with this regimen for this population in clinical practice OBJECTIVE To determine the dose-limiting toxicity ( DLT ) and the maximum-tolerated dose ( MTD ) of combination chemotherapy with leucovorin-modulated weekly bolus 5-fluorouracil ( 5-FU ) and weekly paclitaxel in patients with advanced gastric cancer ( GC ) . METHODS Chemotherapy-naive patients with histologically proven metastatic or recurrent GC were enrolled .  Paclitaxel was administered as a 1-h intravenous ( i.v . ) infusion followed by 5-FU as a bolus i.v . infusion on Days 1 , 8 and 15 . A 2-h i.v . infusion of l-leucovorin was started at the same time as the paclitaxel infusion on Days 1 , 8 and 15 . Treatment cycles were repeated every 28 days until disease progression or unacceptable toxicity occurred . Patients were scheduled to receive 5-FU , l-leucovorin and paclitaxel at four dose levels ( mg/m(2)/week ) : 500/250/60 ( level 1 ) , 500/250/80 ( level 2 ) , 600/250/80 ( level 3 ) and 600/250/100 ( level 4 ) , respectively . RESULTS Eighteen patients were enrolled . During the first cycle of the highest dose level ( level 4 ) , two of the six patients had DLT involving Grade 3 diarrhea and Grade 3 skin rash . Furthermore , three of the four patients who received the second consecutive cycle of treatment at dose level 4 had Grade 4 neutropenia . Dose level 3 was thus determined to be the MTD . Eleven ( 61 % ) of the 18 patients had partial responses , and the median progression-free survival time was 6.8 months . CONCLUSIONS The MTD and the recommended dose for phase II studies of this regimen were determined to be 5-FU 600 mg/m(2)/week , l-leucovorin 250 mg/m(2)/week and paclitaxel 80 mg/m(2)/week 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 BACKGROUND & OBJECTIVE Abdominal recurrence from exfoliated cancer cells contributes a lot to treatment failure of advanced gastric cancer .  Intraperitoneal chemotherapy , which has been proved effective in eliminating exfoliated cancer cells in abdominal cavity , is a hot topic on treatment of gastric cancer . This study was to explore application of combined therapy of intraoperative hypotonic peritoneal chemo-hyperthermia and early postoperative intraperitoneal chemotherapy to gastric cancer . METHODS A total of 156 gastric cancer patients were r and omized into 3 groups , and underwent the combined therapy ( treatment group 1 ) , intraoperative chemotherapy ( treatment group 2 ) , and peritoneal lavage with distilled water ( control group ) , respectively . RESULTS The 2-year survival rate of treatment group 1 was significantly higher than that of control group ( 88.4 % vs. 65.2 % , P < 0.05 ) . The 3-year survival rate of treatment group 1 was significantly higher than those of treatment group 2 , and control group ( 71.1 % vs. 50.0 % , and 45.6 % , P < 0.05 ) . Occurrence of liver metastasis was significantly lower in treatment groups 1 and 2 than in control group ( 7.7 % , and 10.2 % vs. 27.3 % , P < 0.05 ) . CONCLUSIONS Combined therapy of intraoperative hypotonic chemo-hyperthermia and early postoperative intraperitoneal chemotherapy is effective for gastric cancer . Intraperitoneal chemotherapy can be used to prevent postoperative liver metastasis of gastric cancer BACKGROUND The aim of the study was to evaluate the efficacy of adjuvant chemotherapy on survival after resection for gastric cancer . METHODS Patients were enrolled if they underwent resection of gastric cancer but had lymph node or serosal involvement or both . Surgical resection was either total or partial gastrectomy according to the site of the tumor , and surgeons were allowed to perform either D1 or D2 gastrectomy . The subjects were r and om assigned in two treatment groups as follows : surgery alone as the control group , or surgery and adjuvant chemotherapy . Nine cycles of 5 days protocol every 4 weeks was proposed to the patients of the chemotherapy group . The protocol included a daily administration of 200 mg/m(2 ) of folinic acid , 5-fluorouracil ( 375 mg/m(2 ) during the first session increasing 25 mg by session until reaching 500 mg/m(2 ) ) and CDDP 15 mg/m(2 ) . Two hundred patients were required .  Kaplan-Meier survival curves were compared according to the log-rank and the Mantel-Haenszel methods . RESULTS In all , 205 patients were enrolled in the study ; 104 had surgery alone and 101 had surgery and adjuvant chemotherapy .  The patients ' characteristics were similar except for the mean age , which was 4 years less in the control group . Because of toxicity , 54 % of the patients stopped the protocol before the end of the nine courses , and 46 % of the patients received the nine courses including 32 % with a decreased dose and 14 % with a full dose . The 5-year survival rate was 39 % in the control group and 39 % in the chemotherapy group . CONCLUSIONS This protocol of adjuvant chemotherapy failed to improve the 5-year survival after resection for gastric cancer Abstract Background : The high incidence of locoregional recurrences and distant metastases after curative surgery for gastric cancer calls for improved locoregional control and systemic adjuvant treatment . Methods : In a r and omized clinical trial on adjuvant FAM2 chemotherapy , quality of surgery was evaluated by comparing surgical and pathology data . Univariate and multivariate analysis was made to evaluate the effect of prognostic factors on survival and time of recurrence in relation to patients , tumor , and therapy . Results : Of 314 patients r and omized from 28 European institutions , 159 comprised the control and 155 the FAM2 group .  After a median follow-up of 80 months , no statistically significant difference was found between survivals . However , for recurrence time , treated patients had a significant advantage over controls ( p=0.02 ) . At univariate analysis , statistically significant differences in survival and time to progression emerged for T , N , disease stage , and “ adequacy ” of surgery . The multivariate analysis retained preoperative Hb level , T , N , and “ adequacy ” of surgery for time of survival ; and T , N , “ adequacy ” of surgery and adjuvant chemotherapy  for recurrence time . Conclusions : Disease stage is the most important prognostic factor . “ Adequate ” surgery has an important effect . Adjuvant FAM2 delayed time of recurrence , but did not influence overall survival Adjuvant chemotherapy of gastric cancer after curative resection is still subject to discussion . In this study 137 patients with gastric adenocarcinoma , all with positive nodes , were r and omized after curative resection so that 69 received epidoxorubicin ( EPI ) , leucovorin ( LV ) and 5-fluorouracil ( 5-FU ) on days 1–3 every 3 weeks for 7 months , whereas the remaining 68 did not . After a follow-up period of 5 years , 21 of the 69 treated patients ( 30 % ) and nine controls ( 13 % ) were still alive ; median survival time was 18 months for the controls and 31 months for the patients treated with adjuvant chemotherapy ( P < 0.01 ) . © 2001 Cancer Research The authors evaluated the efficacy of adjuvant chemotherapy with 5‐fluorouracil ( 5‐FU ) plus doxorubicin in gastric carcinoma after D2‐3 curative resection . They also evaluated the effect of dose‐related factors ( delivered total dose/m2 , actual dose intensity [ ADI ] , relative dose intensity [ RDI ] ) of this regimen on patient survival Study objectives : The present study was conducted to evaluate the efficacy and safety of the combination of Oxaliplatin , Leucovorin and 5-FU as second line therapy , following relapse to Gemcitabine , in patients with advanced adenocarcinoma of the pancreas . Patients and methods : Patients with advanced pancreatic cancer previously treated with Gemcitabine were included in the study . All patients had histologically or cytologically confirmed adenocarcinoma of the pancreas that was unresectable , locally advanced or metastatic . Treatment consisted of Oxaliplatin 50 mg/m2 ( 2-hour iv infusion ) , followed by Leucovorin 50 mg/m2 ( i.v . bolus ) and 500 mg/m2 5-FU ( 1-hour iv infusion ) , administered weekly , until unacceptable toxicity or disease progression . Objective tumour response and toxicity were evaluated according to World Health Organisation ( WHO ) criteria . Results : A total of 30 patients , 20 men and 10 women , median age 63 years ( range 52–71 years ) and Karnofsky Performance Status ( PS ) of ≥50 entered the study . The majority of patients ( 96 % ) had locally advanced disease . A total of 380 doses of chemotherapy were delivered , a median of 12 doses per patient . Partial responses were observed in 7 patients ( PR 23.3 % ) , stable disease in 9 ( SD 30.0 % ) , while 14 patients progressed ( PD 46.7 % ) . Improved PS was observed in 18 ( 42.8 % ) patients . Patients that had responded to first-line Gemcitabine treatment were found more likely to respond or stabilize their disease with second-line treatment . The median duration of response was 22 weeks , and median overall survival was 25 weeks , Grade 3/4 toxicity expressed per chemotherapy dose included leukopenia 16 % , anemia 3.2 % , thrombocytopenia 3.2 % , diarrhea 14.2 % , fatigue 16.1 % and neurotoxicity 4.2 % . Eight patients ( 27 % ) suffered a febrile neutropenic event managed successfully with oral antibiotic home therapy , while 17 patients required G-CSF support . There were no treatment related deaths . Conclusions : The combination of Oxaliplatin , Leucovorin and 5-FU was tolerated with manageable toxicity , offering encouraging activity as second-line treatment of patients with advanced or metastatic pancreatic adenocarcinoma , previously treated with Gemcitabine . Additional studies are warranted with this regimen in Gemcitabine relapsed pancreatic cancer patients We have reported that increasing the length of infusion from 5 min to 1 h appeared to substantially reduce the toxicity associated with fluorouracil ( 5-FU ) modulated by leucovorin ( LV ) and interferon alpha-2a ( IFN-alpha ) . This phase II study assessed the antitumor efficacy of this regimen . Patients ( n=38 ) with colorectal cancer received IFN-alpha 5 MU/m(2 ) SC on days 1 - 6 ; on days 2 - 6 , LV 200 mg/m(2 ) IV was given with 5-FU at initial doses of 370 - 425 mg/m(2)/h . The regimen was well-tolerated with no grade 4 toxicity . At 425 mg/m(2 ) 5-FU , grade 3 toxicities included diarrhea ( 8.6 % ) , anorexia , fever and fatigue ( 5.7 % each ) , neutropenia and nausea/vomiting ( 2.9 % each ) . Individuals tolerated 5-FU doses up to 644 mg/m(2 ) . Objective responses occurred in 27 % of 37 patients ; median time to progression and survival were 6.1 and 12.9 months . Only 1 of 25 informative tumor sample s had high-frequency microsatellite instability ( MSI ) , while 7 of 23 assessable patients ( 30 % ) with MSI-negative tumors had an objective response . With 425 mg/m(2 ) , the average 5-FU Cp and AUC(0 - 1 h ) were 37.4 microM and 1161 microM/h . Some 6 patients had extended sampling , and the half-lives of 5-FU and FBAL ( apparent ) were 8.6 and 100.0 min , respectively . A 1-h infusion of 5-FU is well tolerated ; individual dose escalation of 5-FU allows each patient to receive the maximum tolerable dose 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 BACKGROUND / AIMS This study was design ed to clarify the effects of treatment and toxicity between 5-fluorouracil ( 5-FU ) plus bolus infusion of Cisplatin ( CDDP ) and 5-FU plus continuous infusion of low-dose CDDP in advanced gastric cancer . METHODOLOGY Seventy-three patients with advanced gastric cancer were enrolled in this study to compare the antitumor effect and toxicity between the bolus infusion of CDDP and the continuous infusion of low-dose CDDP in combination with the continuous infusion of 5-FU .  Sixty-five eligible patients were divided into two groups : group A : curative resection cases ; and , group B : non-curative , recurrent or inoperable cases . Patients were classified into two arms in each group . One arm of treatment regimen is 5-FU and bolus infusion of CDDP ( A-1 , B-1 ) and the other arm is 5-FU and continuous infusion of low-dose CDDP ( A-2 , B-2 ) . RESULTS Response rates were 9.1 % and 38.5 % in arm B-1 and arm B-2 , respectively , although the difference between the two was not at a significant level . Frequently observed toxicities during the treatment were gastrointestinal symptoms such as nausea , vomiting , and anorexia . The incidence of side effects in arm A-2 and arm B-2 was almost the same as that in arm A-1 and arm B-1 . CONCLUSIONS These results revealed that there was no advantage of low-dose continuous infusion of CDDP with 5-FU in terms of response rate and clinical toxicity in our present study The primary objective was to compare the 3-year survival of rectal cancer patients r and omised postoperatively to  irinotecan ( IRI ) , Leucovorin ( LV ) and bolus 5-fluorouracil ( 5FU ) or LV-bolus 5FU with radiotherapy . Secondary objectives included disease-free survival , local relapse and toxicity .  The study included 321 eligible patients . The treatment consisted of weekly administration of IRI 80 mg/m(2 ) intravenously ( IV ) , LV 200 mg/m(2 ) and 5FU 450 mg/m(2 ) bolus ( arm A ) versus LV 200 mg/m(2 ) and 5FU 450 mg/m(2 ) IV bolus ( arm B ) . One cycle included four infusions and treatment was continued for a total of six cycles . The first cycle was followed by pelvic irradiation plus 5FU . There were no differences between the arms in 3-year overall , disease-free and local relapse-free survival . Grade s 3 and 4 toxicity was similar in both the arms with the exception of leucopaenia , neutropaenia and alopecia , which were higher in the IRI arm . IRI added to adjuvant radiochemotherapy with LV and bolus 5FU was not shown to improve survival , whereas the incidence of severe leucopaenia was significantly higher in the IRI arm Gemcitabine has broad activity in a variety of solid tumors including biliary tract carcinomas . The authors evaluated 6‐month survival , response , and toxicity associated with a combination of gemcitabine , 5‐fluorouracil ( 5‐FU ) , and leucovorin ( LV ) in patients with unresectable or metastatic biliary tract or gallbladder adenocarcinoma ( ACA ) 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 Results of 6589 gastric cancer operations at the Department of Surgery , Seoul National University Hospital , from 1970 to 1990 were reported . About two thirds ( 76.6 % ) were advanced gastric cancer ( stages III and IV ) . The 5-year survival rate of operated stage III gastric cancer was only 30.6 % , with frequent recurrence . Conversely , cell-mediated immunities of advanced gastric cancer patients were significantly decreased . Therefore , to improve the cure rate and to prevent or delay recurrence , curative surgery with confirmation of free resection margins and systematic lymph node dissection of perigastric vessels were performed and followed by early postoperative immunotherapy and chemotherapy ( immunochemosurgery ) in stage III patients . To evaluate the effect of immunochemosurgery , two r and omized trials were studied in 1976 and 1981 . In first trial , 5-fluorouracil , mitomycin C , and cytosine arabinoside for chemotherapy and OK 432 for immunotherapy were used . The 5-year survival rates for surgery alone ( n = 64 ) and immunochemosurgery ( n = 73 ) were 23.4 % and 44.6 % , respectively , a significant difference . In the second trial , there were three groups : group I , immunochemosurgery ( n = 159 ) ; group II , surgery and chemotherapy ( n = 77 ) ; and group III , surgery alone ( n = 94 ) . 5-Fluorouracil and mitomycin C for chemotherapy and OK-432 for immunotherapy were administered for 2 years . The 5-year survival rate of group I was 45.3 % , significantly higher than the 29.8 % of group II and than the 24.4 % of group III . The postoperative 1-chloro-2.4-dinitrobenzene test , T-lymphocyte percentage , phytohemagglutinin- and con-A-stimulated lymphoblastogenesis and the antibody-dependent cell-mediated cytotoxicity test showed more favorable values in the immunochemosurgery group . Therefore , immunochemosurgery is the best multimodality treatment for advanced gastric cancer BACKGROUND Infusional fluorouracil ( 5-FU ) and leucovorin ( LV ) with oxaliplatin is one of the current st and ard regimens for the treatment of patients with metastatic colorectal cancer . Weekly bolus 5-FU with high-dose LV ( Roswell Park Memorial Institute Regimen : RPMI ) is the most commonly used regimen in Japan . The objectives of this study were to determine the recommended dose ( RD ) of RPMI combined with oxaliplatin and to evaluate the toxicity and efficacy at the RD . METHODS The subjects were 18 patients with metastatic colorectal cancer .  Oxaliplatin ( 85 mg/m2 ) was given intravenously over 2 h on days 1 and 15 with l-LV ( 250 mg/m2 ) given intravenously over 2 h and 5-FU as an intravenous bolus on days 1 , 8 , and 15 . This treatment was repeated every 4 weeks . The dose of 5-FU was escalated from 400 mg/m2 ( level 1 ) to 500 mg/m2 ( level 2 ) . RESULTS A total of 14 patients received level 1 , and 4 received level 2 . Three of the patients had dose-limiting toxicity ( DLT ) in cycle 1 of level 2 ( grade 3 thrombocytopenia , grade 4 neutropenia and grade 2 neutropenia in one patient each ) , requiring that treatment was delayed for longer than 7 days . None of the 14 patients given level 1 had DLT or grade 3 or 4 gastrointestinal toxicity . Sensory neuropathy occurred in all patients . Objective response rates were 61 % in the 18 patients studied and 64 % at level 1 . The median time to progression was 171 days , and the median overall survival time was 603 days in the 18 patients studied . CONCLUSIONS Oxaliplatin ( 85 mg/m2 ) with weekly bolus 5-FU ( 400 mg/m2 ) and high-dose l-LV ( 250 mg/m2 ) is recommended for further phase III studies in patients with metastatic colorectal 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 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 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
Abstract This is a review of r and omized controlled trials of intravenous 5-flurorouracil ( 5- FU)-containing chemotherapy after curative resection versus surgery alone in patients with gastric carcinoma to determine the impact on survival rate , safety and economics .