Neoadjuvant chemotherapy for high-grade advanced gastric cancer The effects of neoadjuvant chemotherapy on resectability of locally-advanced gastric adenocarcinoma: a clinical trial. [A clinical study of paclitaxel combined with FOLFOX4 regimen as neoadjuvant chemotherapy for advanced gastric cancer]. A favorable impact of preoperative FPLC chemotherapy on patients with gastric cardia cancer. [Long-term outcome of preoperative chemotherapy with 5'-deoxy-5-fluorouridine (5'-DFUR) for gastric cancer]. Upper abdominal stop-flow perfusion as a neo and adjuvant hypoxic regional chemotherapy for resectable gastric carcinoma. A prospective randomized clinical trial. Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European Organisation for Research and Treatment of Cancer randomized trial 40954. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial.
Fifty-five patients with high- grade advanced gastric cancer in whom the presence of stage IV was confirmed by preoperative diagnostic imaging were treated with PMUE therapy by a combined use of cisplatin ( CDDP ) 75 mg/m2 , mitomycin C ( MMC ) 10 mg/body , etoposide 150 mg/body , and UFT ( a combination of 1-(2-tetrahydrofuryl)-5-fluorouracil and uracil in a molar ratio of 1∶4 ) 400 mg/day . CDDP and MMC was administered intravenously on the first day , followed by etoposide 50 mg/day on the 3rd , 4th , and 5th days . All the patients had measurable lesions that were evaluated by computed tomography scanning before and after the treatments . These patients were allocated r and omly to two groups . Of these cases , 29 belonged to the neoadjuvant chemotherapy ( NAC ) group to whom PMUE therapy was given preoperatively ; the remaining 26 patients underwent operation first and received PMUE thereafter ( control group ) . Background factors did not differ significantly between the two groups . The response rate was higher in the NAC group than in the control group ( 62 % in the former versus 35 % in the latter ) . The resectability rates were 79 % and 88 % in the NAC and control groups , respectively . However , the rate of potentially curable cases was higher in the NAC group than in the control group ( 38 % in the former versus 15 % in the latter ) . Among the nonresection cases , the prognosis was highly unfavorable in both groups . In the resection cases , however , the survival rate was significantly better in the NAC group than in the control group . These results may indicate that in patients with high- grade , advanced gastric cancer initial chemotherapy ( neoadjuvant chemotherapy ) and then surgery should be considered . RésuméCinquante-cinq cas de cancer gastrique avancé , à potentiel très malin ( stade IV à l'imagerie préopératoire ) , ont été traités par une chimiothérapie PMUE comprenant une combinaison de CDDP , 75 mg/m2 , MMC , 10 mg/Kg poids corporel , d'etopocide , 150 mg/Kg poids corporel et d'UFT , 400 mg/jour . Le CDDP et le MMC ont été donnés par voie intraveineuse à Jl , suivis d'etoposide , 50 mg/jour aux jours 3 , 4 et 5 . Tous les patients avaient des lésions qui ont pu être évaluées par la tomodensitométrie avant et après le traitement . Ces patients ont été r and omisés en deux groupes : 29 ont eu une chimiothérapie néoadjuvante ( CNA ) par le PMUE en préopératoire , alors que les 26 autres ont d'abord été opérés , et ensuite ont reçu une chimiothérapie PMUE ( groupe contrôle ) . Les caractéristiques des deux groupes ne différaient pas de façon significative . Le taux de réponse était plus haut dans le groupe CNA par rapport au groupe contrôle ( 62 % contre 35 % ) . Le taux de résecabilité était respectivement , de 79 et 88 % dans les deux groupes . Le taux de cas potentiellement curables , cependant , était plus élevé dans le groupe CNA par rapport au groupe contrôle ( 38 % contre 15 % ) . Dans les cas de cancer gastrique non réséqués , le pronostic était extrêmement mauvais , quel que soit le groupe . Dans les cancers réséqués , la survie était significativement plus élevée dans le groupe CNA comparé au groupe contrôle . Ces résultats indiquent que chez les patients ayant un cancer gastrique avancé à potentiel très malin , une chimiothérapie néoadjuvante ( d'emblée ) , suivie de chirurgie , peut être le meilleur choix thérapeutique . ResumenCincuenta y cinco casos de cáncer gástrico avanzado , en los cuales se había confirmado el Estado IV mediante imágenes diagnósticas preoperatorias , recibieron quimioterapia PMVE con el uso combinado de cisplatino ( CDDP ) 75 mg/m2 , MMC 10 mg/cuerpo , Ectoposide 150 mg/cuerpo y VHF 400 mg/día . El CDDP y el MMC fueron administrados por vía intravenosa en el primer día , seguidos de Ectoposide 50 mg/día en los días 3 , 4 y 5 . Todos los pacientes exhibían lesiones medibles , las cuales fueron valoradas por escanografía computadorizada antes y después del tratamiento . Los pacientes fueron ubicados al azar en dos grupos ; 29 quedaron en el grupo de la quimioterapia neoadyuvante ( QNA ) en el cual la quimioterapia PMVE fue practicada preoperatoriamente , y los 26 pacientes restantes fueron sometidos primero a operación y luego a quimioterapia PMVE , constituyendose en el grupo de control . Los antecedentes médicos no eran significativamente diferentes en los dos grupos . La respuesta fue mayor en el grupo de QNA en comparación con el grupo control ( 62 % vs 35 % ) . La tasa de resecabilidad fue de 79 % y 88 % en el grupo QNA y en el grupo de control , respectivamente . Sin embargo , la rata de casos potencialmente curables fue más alta en el grupo de QNA , en comparación con el grupo control ( 38 % vs 15 % ) . En los casos no resecados , sin embargo , la tasa de sobrevida fue significativamente superior en el grupo de QNA en comparación con el grupo control . Tales resulados pueden significar que en pacientes con cáncer gástrico de alto grado y en estado avanzado se debe considerar primero la quimioterapia como paso inicial ( quimioterapia neodyuvante ) , y luego la cirugía INTRODUCTION Surgical resection is the only curative treatment for gastric cancer . However , the overall prognosis of gastric adenocarcinoma is poor and advanced disease may even make surgical treatment impossible . It has been theoretically proposed that administration of chemotherapy before surgical resection may down-stage the disease state and facilitate resectability especially in locally-advanced tumors . AIM We wanted to assess the effect of administration of neoadjuvant chemotherapy on tumor resectability in patients with locally-advances gastric adenocarcinoma . MATERIAL S AND METHODS During a r and omized-controlled trial , we divided 60 patients with locally-advanced gastric adenocarcinoma into two groups of neoadjuvant chemotherapy and surgery ( case ) versus surgery alone ( control ) . Because of patient dropouts , we analyzed the results for 22 and 29 patients in case and control groups respectively . The study period was March 21 , 2011 to March 20 , 2014 . A non-r and omized set of 23 patients were also added to the control group ( Multi-center analysis ) . The analysis was repeated for non-r and omized patients ( 22 case patients versus 52 control patients ) . RESULTS The mean age of patients in case and control groups was 58.3 ± 9.1 and 59.7 ± 8.7 years of age respectively ( p > 0.05 ) . Male to female ratio was 15/7 and 41/11 in case and control groups respectively ( p > 0.05 ) . In R and omized patients , 19 patients ( 86.4 % ) were resectable in case group ; while 16 patients ( 55.2 % ) were resectable in control group ( p < 0.05 ) . Multicenter analysis also revealed resectability in 19 patients ( 86.4 % ) and 31 patients ( 59.6 % ) of case and control groups respectively ( p < 0.05 ) . CONCLUSION We conclude that neoadjuvant chemotherapy could increase tumor resectability rate in patients with locally-advanced gastric adenocarcinoma . However , further studies are necessary to confirm the effect of this modality on patients ' overall survival OBJECTIVE To evaluate the clinical efficacy and the toxicity of neoadjuvant chemotherapy with paclitaxel and FOLFOX4 ( 5-fluorouracil/leucovorin combined and oxaliplatin ) regimen for advanced gastric cancer . METHODS Seventy-eight patients with cTNM stage III or IV ( M0 ) gastric cancer were enrolled and 39 were r and omized into the treatment arm ( n=39 , paclitaxel combined with FOLFOX4 regimen neoadjuvant chemotherapy every two weeks in each cycle ) and control group ( n=39 ) . Clinical response was evaluated with RECIST criteria after 3 cycles . Patients in experimental group received surgery after 2 - 4 weeks and postoperative chemotherapy of 3 cycles of the original regimen . When disease progressed , postoperative chemotherapy regimen was changed into ECF regimen . The control group of 39 patients received surgery within 2 weeks and postoperative chemotherapy of 6 cycles of paclitaxel combined with FOLFOX4 regimen . RESULTS The clinical response rate was 66.7 % in the treatment arm . The R0 resection rate ( 59.0 % ) was significantly higher than that in the control group ( P=0.025 ) and the number of lymph node metastasis in the treatment arm(3.23±2.80 ) was significantly lower than that in the control group ( 5.79±2.69 , P=0.001 ) . There were no significant differences in postoperative complication rate ( 5.1 % vs. 2.6 % ) and the number of lymph node dissection ( 19.69±2.95 vs. 20.59±3.22 ) between the two groups ( P>0.05 ) . The median survival time and 2-year survival rate in the treatment arm [ ( 27.10±2.32 ) months and 59.0 % ] was significantly higher than that in the control group[(18.20±1.30 ) months and 28.2 % ] ( P=0.001 , P=0.006 ) . Cox regression multivariable analysis showed that tumor differentiation , R0 resection , lymph node metastasis were independent prognostic factors . Adverse reaction of chemotherapy , mainly hematological adverse reactions , and peripheral nerve toxicity , were tolerable . No significant differences were noted between the two groups in adverse reactions ( P>0.05 ) . CONCLUSIONS The efficacy of paclitaxel combined with FOLFOX4 as neoadjuvant chemotherapy is high . Patients tolerance and compliance are satisfactory . It can improve in patients with advanced gastric cancer the R0 resection rate , reduce lymph node metastasis and improve survival The aim of this study is to evaluate the effects of preoperative chemotherapy with fluorouracili polyphase liposome composita pro orale ( FPLC ) on the tumour cells and the survival rate of the patients with gastric cardia cancer . Sixty patients with gastric cardia cancer were r and omly divided into two groups . Thirty patients were treated with FPLC prior to surgical resection , the other 30 , as controls , did not receive the preoperative chemotherapy . Pathological responses of the tumours to the FPLC chemotherapy were determined by gross and microscopic assessment s of tumour size , tumour emboli , cell degeneration and necrosis . Expressions of nm23 and CD44 were detected by flow cytometry . All patients were followed up to 5 years . In the FPLC-treated patients , the tumour size ( p<0 . 01 ) , the number of tumour emboli ( p=0.04 ) and the intensity of CD44 expression ( p<0.001 ) , were significantly reduced , while cell degeneration ( p<0.001 ) , necrosis ( p<0.01 ) and the expression of nm23 ( p<0.001 ) were increased , when compared with those observations seen in the controls . The postoperative 5-year survival rate was 40 % in the FPLC-treated group and 23 % in the controls ( p=0.17 ) . Preoperative FPLC chemotherapy might improve the survival rate of patients with gastric cardia cancer by inhibiting tumour proliferative , invasive and metastatic activities , and stimulating the patient 's immune system We performed a multicenter clinical trial of preoperative chemotherapy for gastric cancer . Patients aged 75 years or less with advanced gastric cancer were enrolled and r and omized into the following groups : Group I , which received oral 5'-DFUR ( 610 mg/m2/day x 10 days or over ) preoperatively , and Group II , which received no treatment preoperatively . Patients in both groups also received intravenous MMC 1 and 2 days after surgery and were orally administered 5'-DFUR for two years postoperatively . There were 171 patients ( Group I : 91 , Group II : 80 ) enrolled and analyzed , and the  5-year survival rate  was 63.4 % in Group I and 64.9 % in Group II ( p = 0.698 ) . Among patients classified as having curability B , the 5-year survival rate of each group was 51.8 % and 36.8 % , respectively ( p = 0.426 ) . However , the 5-year survival rate of patients showing good compliance with oral 5'-DFUR therapy was significantly higher than that of patients with poor compliance ( 53.3 % vs 22.0 % , p = 0.010 ) . The pyrimidine nucleoside phosphorylase ( PyNPase ) activity in gastric carcinoma tissue from Group I was lower than that from Group II , and Group II patients tended to die of hematogeneous metastases . In conclusion , although this clinical trial failed to demonstrate a significant benefit of preoperative chemotherapy because of the low dose of 5'-DFUR , we believe that good compliance with oral anticancer treatment contributes to long-term survival and that 5'-DFUR reduces hematogeneous metastasis of gastric carcinoma 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 PURPOSE Patients with locally advanced gastric cancer benefit from combined pre- and postoperative chemotherapy , although fewer than 50 % could receive postoperative chemotherapy . We examined the value of purely preoperative chemotherapy in a phase III trial with strict preoperative staging and surgical resection guidelines . PATIENTS AND METHODS Patients with locally advanced adenocarcinoma of the stomach or esophagogastric junction ( AEG II and III ) were r and omly assigned to  preoperative chemotherapy followed by surgery or to surgery alone . To detect with 80 % power an improvement in median survival from 17 months with surgery alone to 24 months with neoadjuvant , 282 events were required . RESULTS This trial was stopped for poor accrual after 144 patients were r and omly assigned ( 72:72 ) ; 52.8 % patients had tumors located in the proximal third of the stomach , including AEG type II and III . The International Union Against Cancer R0 resection rate was 81.9 % after neoadjuvant chemotherapy as compared with 66.7 % with surgery alone ( P = .036 ) . The surgery-only group had more lymph node metastases than the neoadjuvant group ( 76.5 % v 61.4 % ; P = .018 ) . Postoperative complications were more frequent in the neoadjuvant arm ( 27.1 % v 16.2 % ; P = .09 ) . After a median follow-up of 4.4 years and 67 deaths , a survival benefit could not be shown ( hazard ratio , 0.84 ; 95 % CI , 0.52 to 1.35 ; P = .466 ) . CONCLUSION This trial showed a significantly increased R0 resection rate but failed to demonstrate a survival benefit . Possible explanations are low statistical power , a high rate of proximal gastric cancer including AEG and /or a better outcome than expected after radical surgery alone due to the high quality of surgery with resections of regional lymph nodes outside the perigastic area ( celiac trunc , hepatic ligament , lymph node at a. lienalis ; D2 ) BACKGROUND A regimen of epirubicin , cisplatin , and infused fluorouracil ( ECF ) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma . We assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer . METHODS We r and omly assigned patients with resectable adenocarcinoma of the stomach , esophagogastric junction , or lower esophagus to either perioperative chemotherapy and surgery ( 250 patients ) or surgery alone ( 253 patients ) . Chemotherapy consisted of three preoperative and three postoperative cycles of intravenous epirubicin ( 50 mg per square meter of body-surface area ) and cisplatin ( 60 mg per square meter ) on day 1 , and a continuous intravenous infusion of fluorouracil ( 200 mg per square meter per day ) for 21 days . The primary end point was overall survival . RESULTS  ECF-related adverse effects were similar to those previously reported among patients with advanced gastric cancer .  Rates of postoperative complications were similar in the perioperative-chemotherapy group and the surgery group ( 46 percent and 45 percent , respectively ) , as were the numbers of deaths within 30 days after surgery . The resected tumors were significantly smaller and less advanced in the perioperative-chemotherapy group . With a median follow-up of four years , 149 patients in the perioperative-chemotherapy group and 170 in the surgery group had died . As compared with the surgery group , the perioperative-chemotherapy group had a higher likelihood of overall survival ( hazard ratio for death , 0.75 ; 95 percent confidence interval , 0.60 to 0.93 ; P=0.009 ; five-year survival rate , 36 percent vs. 23 percent ) and of progression-free survival ( hazard ratio for progression , 0.66 ; 95 percent confidence interval , 0.53 to 0.81 ; P<0.001 ) . CONCLUSIONS In patients with operable gastric or lower esophageal adenocarcinomas , a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival . ( Current Controlled Trials number , IS RCT N93793971 [ controlled-trials.com ] . ) PURPOSE After curative resection , the prognosis of gastroesophageal adenocarcinoma is poor . This phase III trial was design ed to evaluate the benefit in overall survival ( OS ) of perioperative fluorouracil plus cisplatin in resectable gastroesophageal adenocarcinoma . PATIENTS AND METHODS Overall , 224 patients with resectable adenocarcinoma of the lower esophagus , gastroesophageal junction ( GEJ ) , or stomach were r and omly assigned to either  perioperative chemotherapy and surgery ( CS group ; n = 113 ) or surgery alone ( S group ; n = 111 ) . Chemotherapy consisted of two or three preoperative cycles of intravenous cisplatin ( 100 mg/m(2 ) ) on day 1 , and a continuous intravenous infusion of fluorouracil ( 800 mg/m(2)/d ) for 5 consecutive days ( days 1 to 5 ) every 28 days and three or four postoperative cycles of the same regimen . The primary end point was OS . RESULTS Compared with the S group , the CS group had a better OS ( 5-year rate 38 % v 24 % ; hazard ratio [ HR ] for death : 0.69 ; 95 % CI , 0.50 to 0.95 ; P = .02 ) ; and a better disease-free survival ( 5-year rate : 34 % v 19 % ; HR , 0.65 ; 95 % CI , 0.48 to 0.89 ; P = .003 ) . In the multivariable analysis , the favorable prognostic factors for survival were perioperative chemotherapy ( P = .01 ) and stomach tumor localization ( P < .01 ) . Perioperative chemotherapy significantly improved the curative resection rate ( 84 % v 73 % ; P = .04 ) . Grade 3 to 4 toxicity occurred in 38 % of CS patients ( mainly neutropenia ) but postoperative morbidity was similar in the two groups . CONCLUSION In patients with resectable adenocarcinoma of the lower esophagus , GEJ , or stomach , perioperative chemotherapy using fluorouracil plus cisplatin significantly increased the curative resection rate , disease-free survival , and OS
Background Neoadjuvant chemotherapy ( NAC ) is extensively used in the treatment of patients with gastric cancer ( GC ) , particularly in high risk , advanced gastric cancer .
Previous trials testing the efficacy of NAC have reported inconsistent results .
Methods This study compares the combined use of NAC and surgery with surgery alone for GC by using a meta-analytic approach .