Pathological prognostic factors in the second British Stomach Cancer Group trial of adjuvant therapy in resectable gastric cancer. Effects of continuous hyperthermic peritoneal perfusion on prognosis of gastric cancer with serosal invasion. Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Improves Survival of Patients with Peritoneal Carcinomatosis from Gastric Cancer: Final Results of a Phase III Randomized Clinical Trial Type-oriented Intraoperative and Adjuvant Chemotherapy and Survival after Curative Resection of Advanced Gastric Cancer 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. Prophylaxis and treatment of peritoneal carcinomatosis: Intraperitoneal chemotherapy with mitomycin C bound to activated carbon particles Methods for combining randomized clinical trials: strengths and limitations. Indications for Early Postoperative Intraperitoneal Chemotherapy of Advanced Gastric Cancer: Results of a Prospective Randomized Trial [Clinical application of perioperative continuous hyperthermic peritoneal perfusion chemotherapy for gastric cancer]. [Efficacy of intraoperative hypotonic peritoneal chemo-hyperthermia combined with early postoperative intraperitoneal chemotherapy on gastric cancer]. Randomized clinical trial of adjuvant chemotherapy with intraperitoneal and intravenous cisplatin followed by oral fluorouracil (UFT) in serosa-positive gastric cancer versus curative resection alone: final results of the Japan Clinical Oncology Group trial JCOG9206-2 Capecitabine and oxaliplatin for advanced esophagogastric cancer. Phase II study with the combination etoposide, doxorubicin, and cisplatin in advanced measurable gastric cancer. Intraoperative chemohyperthermic peritoneal perfusion as an adjuvant to gastric cancer: final results of a randomized controlled study. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. Clinical efficacy of S-1 combined with cisplatin for advanced 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 Continuous hyperthermic peritoneal perfusion for the prevention of peritoneal recurrence of gastric cancer: Randomized controlled study Successful intraperitoneal hyperthermic chemoperfusion for the prevention of postoperative peritoneal recurrence in patients with advanced gastric carcinoma Extensive Intraoperative Peritoneal Lavage as a Standard Prophylactic Strategy for Peritoneal Recurrence in Patients with Gastric Carcinoma [Evaluation of TS-1 combined with cisplatin for neoadjuvant chemotherapy in patients with advanced gastric cancer]. Prophylactic therapy for peritoneal recurrence of gastric cancer by continuous hyperthermic peritoneal perfusion with mitomycin C Prophylaxis with carbon-adsorbed mitomycin against peritoneal recurrence of gastric cancer Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer.
The second British Stomach Cancer Group trial was a prospect i ve r and omised controlled trial of adjuvant radiotherapy or cytotoxic chemotherapy after gastrectomy for adenocarcinoma . It recruited between 1981 and 1986 . No survival advantage has been demonstrated for the patients receiving either type of adjuvant therapy compared with those undergoing surgery alone . We report on 436 patients r and omised into the trial together with 203 patients , who did not fulfil the trial criteria , referred to the trial . A univariate ( log-rank ) analysis of pathological factors obtained from the local referring centres showed that tumour size , macroscopic type , number os sites involved , depth of invasion , involvement of resection lines and lymph nodes and histological grade were significant determinants of survival . Histological review by two experienced histopathologists found that the Lauren classification and histological grade , but not the Ming classification , were significant prognostic factors . The degree of lymphocytic and eosinophilic infiltration and presence of dysplasia assessed by one of the pathologists showed a significant correlation with survival . However , inter-observer correlation for these histological parameters and grade was poor . Multivariate analysis identified only depth of invasion , resection line and nodal involvement as significant independent pathological variables influencing survival . This study confirms the need for expert preparation of the resected specimen to obtain the important information on depth of invasion and nodal status and also reveals some variation in histological assessment , particularly grading , in gastric carcinoma OBJECTIVE To evaluate the effects of continuous hyperthermic peritoneal perfusion ( CHPP ) together with st and ard chemotherapy on the prognosis of patients with gastric cancer invading the serosa . DESIGN Retrospective study . SETTING University hospital , Japan . SUBJECTS 174 patients who had undergone curative resection for gastric cancer invading the serosa ( T3 ) between 1980 and 1989 , 78 of whom had been r and omised to be treated with CHPP after operation and 96 who received st and ard chemotherapy .  INTERVENTIONS CHPP was done immediately after operation ; 8 - 10 l fluid containing 80 - 100 mg/m2 mitomycin C was perfused at a rate of 100 - 200 ml/minute , and inflow and out flow temperatures were maintained at 44 - 45 degrees C and 40 - 42 degrees C , respectively . This was followed by a st and ard regimen of mitomycin C and 1-(2-tetrahydrofuryl)-5-fluorouracil/uracil ( 1:4 ) ( UFT ) . The control group received the st and ard regimen only . MAIN OUTCOME MEASURES Five year survival and patterns of recurrence in three groups : no lymph node metastases , 1 - 9 , and 10 or more . RESULTS Only in the group with 1 - 9 lymph node metastases was there an appreciable but not significant difference in 5 year survival : 66 % compared with 44 % ( p = 0.084 ) . The mean disease free survival for patients with peritoneal metastases was 30 months in the CHPP group compared with 23 months among the controls . CONCLUSION CHPP improved prognosis in patients with T3 gastric cancer who had only 1 - 9 metastatic lymph nodes Background This r and omized phase III study was to evaluate the efficacy and safety of cytoreductive surgery ( CRS ) plus hyperthermic intraperitoneal chemotherapy ( HIPEC ) for the treatment of peritoneal carcinomatosis ( PC ) from gastric cancer . Methods Sixty-eight gastric PC patients were r and omized into CRS alone ( n = 34 ) or CRS + HIPEC ( n = 34 ) receiving cisplatin 120 mg and mitomycin C 30 mg each in 6000 ml of normal saline at 43 ± 0.5 ° C for 60–90 min . The primary end point was overall survival , and the secondary end points were safety profiles . Results Major clinicopathological characteristics were balanced between the 2 groups . The PC index was 2–36 ( median 15 ) in the CRS + HIPEC and 3–23 ( median 15 ) in the CRS groups ( P = 0.489 ) . The completeness of CRS score ( CC 0–1 ) was 58.8 % ( 20 of 34 ) in the CRS and 58.8 % ( 20 of 34 ) in the CRS + HIPEC groups ( P = 1.000 ) . At a median follow-up of 32 months ( 7.5–83.5 months ) , death occurred in 33 of 34 ( 97.1 % ) cases in the CRS group and 29 of 34 ( 85.3 % ) cases of the CRS + HIPEC group . The median survival was 6.5 months ( 95 % confidence interval 4.8–8.2 months ) in CRS and 11.0 months ( 95 % confidence interval 10.0–11.9 months ) in the CRS + HIPEC groups ( P = 0.046 ) . Four patients ( 11.7 % ) in the CRS group and 5 ( 14.7 % ) patients in the CRS + HIPEC group developed serious adverse events ( P = 0.839 ) . Multivariate analysis found CRS + HIPEC , synchronous PC , CC 0–1 , systemic chemotherapy ≥ 6 cycles , and no serious adverse events were independent predictors for better survival . Conclusions For synchronous gastric PC , CRS + HIPEC with mitomycin C 30 mg and cisplatin 120 mg may improve survival with acceptable morbidity n= 16 ) ; intraoperative chemotherapy and UFT 300 mg/day ( P1 group , n= 13 ) ; or UFT 600 mg/day ( P2 group , n= 17 ) . Patients with an intestinal type of cancer were r and omly assigned to one of three treatment groups : H0 ( n= 17 ) , H1 ( n= 12 ) , and H2 ( n= 12 ) ; each group was subjected to the same protocol s as the P0 , P1 , and P2 groups , respectively , except for the MMC administration route . MMC ( 10 mg/patient ) was administered intraoperatively into the intraperitoneal cavity ( P1 and P2 groups ) or the portal vein ( H1 and H2 groups ) . All patients underwent curative resection . Background factors did not differ significantly among the treatment groups . The overall survival rates were progressively worsened in the order of P2 , P1 , and P0 or H2 , H1 , and H0 , respectively . The survival rate of the P2 group was statistically higher than that of the P0 group ( p < 0.05 ) . The intermediate-term survival rate of the P2 group or H2 group was significantly higher than that of the P0 group ( p < 0.05 ) or H0 group ( p < 0.05 ) , respectively . These results suggest the effectiveness of this therapy and the possible eradication of potential micrometastatic foci outside the surgical field by the direct administration of chemotherapeutic agents to the predicted recurrence site 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 A novel method of prophylaxis and treatment for peritoneal carcinomatosis — mitomycin C bound to activated carbon particles (MMC-CH)—was tested in patients with advanced gastric cancer in a prospect i ve r and omized study . Activated carbon particles are taken up selectively by lymphatic tissues , which seem to be a primary site of peritoneal carcinomatosis in the peritoneal cavity , and adsorb a large amount of anticancer agent mitomycin C , which is subsequently released slowly and for a protracted period . A group of 113 patients who underwent radical resection for gastric cancer with definite serosal involvement were entered in this trial . Those in the control group received no intraperitoneal anticancer drugs . Patients in the MMC-CH group were given 50 mg mitomycin C as MMC-CH , which was dispersed throughout the peritoneal cavity just before surgical closure . No other anticancer drugs were given to these patients after surgery . The 2- and 3-year survival rates for the MMC-CH group were 42 % and 38 % , respectively ; and the rates for the control group were 28 % and 20 % , respectively . The difference in survival between the two groups was significant at 2 and 3 years ( p<0.05 ) . For the survival of patients with macroscopic peritoneal carcinomatosis , there was no difference between these two groups . For the survival of patients who underwent histologically curative resection , 2- and 3-year survivals for the MMC-CH group were 66 % and 66 % , respectively and for the control group 35 % and 20 % , respectively . The difference between the two groups was statistically significant ( p<0.01 ) at both 2 and 3 years . There was no difference in morbidity after surgery between these two groups , except a bowel ( colocutaneous ) fistula developed in two patients given MMC-CH . There were no operative deaths in this series . RésuméUne nouvelle méthode prophylactique et thérapeutique de la carcinose péritonéale , l'administration de la mitomycine C liée aux particules de carbone activé ( MMC-CH ) , a été testée chez les patients ayant un cancer gastrique au stade avancé dans une étude prospect i ve , r and omisée . Les particules de carbone activé sont absorbées sélectivement par le courant lymphatique qui semble être le premier site de l'atteinte carcinomateuse de la cavité péritonéale . Ceci permet la résorption d'une gr and e quantité de mitomycine C qui est ensuite relarguée lentement pendant une période de temps prolongé . Cent treize patients ayant eu une résection radicale pour cancer gastrique avec une atteinte séreuse sont rentrés dans cet essais . Ceux du groupe contrôle n'ont reçu aucune autre chimiothérapie . Les patients du groupe MMC-CH  ont reçu 50 mg de mitomycine C sous forme de MMC-CH , dispersée dans la cavité péritonéale juste avant la fermeture . Aucun autre médicament chimiothérapeutique a été administré à ces patients après la chimiothérapie intrapéritonéale : La survie à deux et à trois ans dans let groupe MMC-CH a été de 42 et de 38 pour-cent , respectivement , alors que les taux de survie du groupe contrôle étaient de 28 et de 20 pour-cent , respectivement . La différence de survie à 2 et à ans était statistiquement significantive ( p<0.05 ) . Chez les patients ayant une carcinose péritonéale macroscopique , les taux de survie ne présentaient aucune différence statistiquement significative entre les deux groupes . La survie à 2 et à 3 ans des patients ayant eu une résection histologiquement curative , étaient de 66 % et 66 % pour le groupe MMC-CH , et de 36 et de 20 pour-cent , respectivement . La différence entre les deux groupes était statistiquement significative ( p<0.01 ) à 2 et à 3 ans . II n'y avait aucune différence de morbidité après chirurgie dans les deux groupes excepté le développement de deux fistules intestinales ( colo-cutanée ) chez deux patients du group MMC-CH . II n'y avait aucune mortalité dans cette série . ResumenSe ensayó un novel método de profilaxis y tratamiento de la carinomatosis peritoneal , la mitomicina C ligada a partículas activadas de carbón ( MMC-CH ) , fue probado en pacientes con cáncer gástrico avanzado en un estudio prospect ivo y r and omizado . Las Partículas activadas de carbón son tomadas en forma selectiva por los tejidos linfáticos , los cuales parecen ser una ubicación primaria de la carcinomatosis peritoneal , y absorben una gran cantidad del agente anticancerígeno , la mitomicina C , la cual es subsiguientemente liberada en forma lenta y durante un periodo prolongado . 113 pacientes sometidos a resección radical por cáncer gástrico con clara afección de la serosa fueron ingresados al estudio . Los pcientes del grupo control no recibieron drogas anticancerígenas intraperitoneales . Los pacientes en el grupo MMC-CH recibieron 50 mg de mitomicina C como MMC-CH , que se dispersó a través de la cavidad peritoneal justo antes de iniciar el cierre de la herida . No se administró agente anticancerígeno diferente luego de la cirugía . Las tasas de sobrevida a 2 y 3 años para el grupo MMC-CH fueron 42 y 38 % respectivamente , y las del grupo control fueron 28 y 20 % respectivamente . La diferencia en sobrevida entre estos dos grupos fue significativa a los 2 y 3 años ( p<0.05 ) . No se encontró diferencia entre los dos grupos en los pacientes que sobrevivieron con carcinomatosis peritoneal macroscópica . En la supervivencia de pacientes que recibieron resección histológicamente curativa , las tasas de sobrevida a 2 y 3 años para el grupo MMC-CH fueron 66 y 66 % respectivamente y para el grupo control 35 y 20 % respectivamente . La diferencia entre los dos grupos fue estadísticamente significative ( p<0.01 ) a los 2 y 3 años . No se halló diferencia en cuanto a morbilidad postoperatoria entre estos dos grupos , excepto por fístula del colon ( fístula colo-cutánea ) que apareció en dos pacientes del grupo MMC-CH . No se registraron muertes operatorias en la serie Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . Previous analysis of this prospect i ve r and omized trial and meta- analysis of published r and omized trials of adjuvant intraperitoneal chemotherapy demonstrated improved survival in patients with advanced gastric cancer . Simple criteria applicable at the time of surgery for patient selection were sought in this analysis . From 1990 to 1995 a series of 248 patients with biopsy-proven gastric cancer were r and omized intraoperatively to receive early postoperative intraperitoneal mitomycin C and 5-fluorouracil ( 125 patients ) versus surgery only ( 123 patients ) . Gastric resection plus early postoperative intraperitoneal chemotherapy showed improved overall survival compared to surgery only ( 54 % and 38 % , respectively ; p= 0.0278 ) . There were statistically significant differences in patients with stage III ( 57 % and 23 % , respectively ; p= 0.0024 ) and in those with stage IV ( 28 % and 5 % , respectively ; p= 0.0098 ) gastric cancer . The improvement in survival rate was statistically significant for the subgroup of patients with gross serosal invasion ( 52 % and 25 % , respectively ; p= 0.0004 ) and patients with lymph node metastasis ( 46 % and 22 % , respectively ; p= 0.0027 ) . The surgeons ' impression about lymph node status was unreliable , but assessment of serosal invasion was accurate in 80 % of cases . Gross serosal invasion with or without frozen section evaluation of lymph nodes can be used as the major selection criteria for early postoperative intraperitoneal chemotherapy of advanced gastric cancer OBJECTIVE To evaluate the clinical effect of intraoperative and early postoperative continuous hyperthermic pertioneal perfusion chemotherapy ( CHPPC ) for gastric cancer . METHODS Eight-five patients with gastric cancer were r and omized into therapeutic group with perioperative CHPPC combined with intravenous chemotherapy ( n=44 ) and control group with intravenous chemotherapy only ( n=41 ) . The postoperative complications , adverse effects , local recurrence rates , distant metastasis rates , and 1- and 3-year survival rates were compared between two groups . RESULTS No significant differences were found in the postoperative complications and adverse effects between the two groups . The recurrence rate and distant metastasis rates in the therapeutic group were significantly lower than those in the control group ( 20.45 % vs 43.90 % , and 15.90 % vs 39.02 % , P<0.05 ) . The 1- and 3-year survival rates in the therapeutic group were significantly higher than those in the control group ( 90.90 % vs 78.05 % , and 59.09 % vs 34.15 % , P<0.05 ) . CONCLUSION Perioperative CHPPC for gastric cancer is safe and feasible , and can reduce the recurrence rate , distant metastasis rate and improve the survival for gastric cancer patient after operation 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 Purpose To evaluate the survival benefit of adjuvant chemotherapy after curative resection in serosa-positive gastric cancer , a multicenter phase III clinical trial was conducted in Japan . Patients and methods From January 1993 to March 1998 , 268 patients were r and omized to adjuvant chemotherapy ( 135 patients ) or surgery alone ( 133 patients ) . All patients underwent gastrectomy with D2 or greater lymph node dissection . The chemotherapy regimen consisted of intraperitoneal cisplatin soon after abdominal closure , postoperative intravenous cisplatin ( day 14 ) and 5-fluorouracil ( day 14–16 ) , and daily oral FU ( UFT ) starting 4 weeks after surgery for 12 months . The primary endpoint was overall survival . Relapse-free survival and site of recurrence were secondary endpoints . Results Fifty-two patients ( 38.5 % ) in the adjuvant chemotherapy arm completed the chemotherapy regimen . There were 4 ( 1.49 % ) treatment-related deaths , 1 in the surgery-alone and 3 in the adjuvant chemotherapy arm ( 2 did not receive chemotherapy ) . Grade 4 toxicity was observed in 3 patients in the surgery-alone and 2 patients in the adjuvant chemotherapy arm . There was no significant difference in 5-year overall survival ( 62.0 % adjuvant chemotherapy vs. 60.9 % surgery-alone , P = 0.482 ) and 5-year relapse-free survival rates ( 57.5 % adjuvant chemotherapy vs. 55.6 % surgery-alone ; P = 0.512 ) . Conclusion There was no benefit in overall and relapse-free survival with this adjuvant chemotherapy regimen for patients with macroscopically serosa-positive gastric cancer after curative resection BACKGROUND We evaluated capecitabine ( an oral fluoropyrimidine ) and oxaliplatin ( a platinum compound ) as alternatives to infused fluorouracil and cisplatin , respectively , for untreated advanced esophagogastric cancer . METHODS In a two-by-two design , we r and omly assigned 1002 patients to receive triplet therapy with epirubicin and cisplatin plus either fluorouracil ( ECF ) or capecitabine ( ECX ) or triplet therapy with epirubicin and oxaliplatin plus either fluorouracil ( EOF ) or capecitabine ( EOX ) . The primary end point was noninferiority in overall survival for the triplet therapies containing capecitabine as compared with fluorouracil and for those containing oxaliplatin as compared with cisplatin . RESULTS For the capecitabine-fluorouracil comparison , the hazard ratio for death in the capecitabine group was 0.86 ( 95 % confidence interval [ CI ] , 0.80 to 0.99 ) ; for the oxaliplatin-cisplatin comparison , the hazard ratio for the oxaliplatin group was 0.92 ( 95 % CI , 0.80 to 1.10 ) . The upper limit of the confidence intervals for both hazard ratios excluded the predefined noninferiority margin of 1.23 . Median survival times in the ECF , ECX , EOF , and EOX groups were 9.9 months , 9.9 months , 9.3 months , and 11.2 months , respectively ; survival rates at 1 year were 37.7 % , 40.8 % , 40.4 % , and 46.8 % , respectively . In the secondary analysis , overall survival was longer with EOX than with ECF , with a hazard ratio for death of 0.80 in the EOX group ( 95 % CI , 0.66 to 0.97 ; P=0.02 ) . Progression-free survival and response rates did not differ significantly among the regimens . Toxic effects of capecitabine and fluorouracil were similar . As compared with cisplatin , oxaliplatin was associated with lower incidences of grade 3 or 4 neutropenia , alopecia , renal toxicity , and thromboembolism but with slightly higher incidences of grade 3 or 4 diarrhea and neuropathy . CONCLUSIONS Capecitabine and oxaliplatin are as effective as fluorouracil and cisplatin , respectively , in patients with previously untreated esophagogastric cancer . ( Current Controlled Trials number , IS RCT N51678883 [ controlled-trials.com ] . ) In this phase II multicenter trial , 67 evaluable patients with advanced measurable gastric carcinoma were treated with a combination of etoposide , Adriamycin ( doxorubicin ; Adria Laboratories , Columbus , OH ) , and cisplatin ( EAP ) . The overall response rate was 64 % , including 21 % complete responses ( CRs ) . In 55 patients with metastatic disease , 31 responses ( 51 % ) including eight CRs ( 15 % ) were achieved . Responses were seen in all metastatic sites , but the response rate was lower in patients with peritoneal carcinomatosis . In 12 patients with locoregional disease , six CRs and six partial responses ( PRs ) were observed . Eight CRs ( three and five in patients with metastatic and locoregional disease , respectively ) were pathologically confirmed . The overall median response duration was 7 months ; it was 16 months for patients achieving CR ( 22 months for pathologically confirmed CR [ pCR ] ) , and 6 months for PR . The median survival time for all patients was 9 months , for the patients who achieved CR 17 months , for pCR 23 months , and for PR 9.5 months . Median survival time for all patients with metastatic disease was 8 months , and for locoregional disease 12.5 months . Six patients ( 9 % ) ( four local , two metastatic disease ) were alive at 2 years , and four patients are alive and disease free at 35 + to 56 + months . Main toxicities were leukopenia and thrombocytopenia , with 64 % of patients developing grade 3 to 4 myelosuppression and 12 % severe infections . Nonhematologic toxicities of World Health Organization ( WHO ) grade 4 were not observed BACKGROUND / AIMS Although the most frequent cause of death after curative resection of advanced gastric cancer is peritoneal recurrence , there was no effective therapy for the prevention of peritoneal recurrence . This r and omized trial sought to determine whether intraoperative chemohyperthermic peritoneal perfusion could eliminate microscopic residual disease and thereby improve survival of patients with advanced gastric cancer . METHODOLOGY One-hundred and thirty-nine patients with T2 - 4 gastric cancer underwent curative gastrectomy with extended lymphadenectomy .  These patients were r and omly allocated into the following three groups . Patients in the CHPP group received surgery + chemohyperthermic peritoneal perfusion , and those in the CNPP group underwent surgery + chemonormothermic peritoneal perfusion . The third group was surgery alone group . In the CHPP and CNPP groups , peritoneal cavity was perfused with 6 - 8 liters of heated saline at , respectively , 42 - 43 degrees C and 37 degrees C with 30 mg of mitomycin C and 300 mg of cisplatin by a extracorporeal circulation machine . RESULTS Major operative complication occurred in 19 % ( 9/48 ) , 14 % ( 6/44 ) and 19 % ( 9/47 ) of the CHPP , CNPP and surgery alone group , respectively . Complication which uniquely developed after chemohyperthermic peritoneal perfusion was bowel perforation . Mortality rates of each group were 4 % ( 2/48 ) , 0 % ( 0/44 ) and 4 % ( 2/47 ) in the CHPP , CNPP and surgery alone group , respectively . Overall 5-year survival rates of CHPP , CNPP and surgery alone groups were 61 % , 43 % and 42 % , respectively . In a subset analysis , patients with gastric cancer having serosal invasion or lymph node metastasis have shown a statistically significant improvement in survival when treated with chemohyperthermic peritoneal perfusion . However , chemonormothermic peritoneal perfusion had no survival benefit . By analyzing with Cox proportional hazard model , chemohyperthermic peritoneal perfusion emerged as an independent prognostic factor for good survival . Surgery alone had three-fold higher risk of death than chemohyperthermic peritoneal perfusion . CONCLUSIONS Chemohyperthermic peritoneal perfusion had an efficiency for the prophylaxis of recurrence after curative resection of advanced gastric cancer , and is indicated for patients with tumor infiltrating beyond serosal layer and node positive tumor PURPOSE This r and omized phase II trial evaluated two docetaxel-based regimens to see which would be most promising according to overall response rate ( ORR ) for comparison in a phase III trial with epirubicin-cisplatin-fluorouracil ( ECF ) as first-line advanced gastric cancer therapy . PATIENTS AND METHODS Chemotherapy-naïve patients with measurable unresectable and /or metastatic gastric carcinoma , a performance status < or= 1 , and adequate hematologic , hepatic , and renal function r and omly received < or= eight 3-weekly cycles of ECF ( epirubicin 50 mg/m(2 ) on day 1 , cisplatin 60 mg/m(2 ) on day 1 , and fluorouracil [ FU ] 200 mg/m(2)/d on days 1 to 21 ) , TC ( docetaxel initially 85 mg/m(2 ) on day 1 [ later reduced to 75 mg/m(2 ) as a result of toxicity ] and cisplatin 75 mg/m(2 ) on day 1 ) , or TCF ( TC plus FU 300 mg/m(2)/d on days 1 to 14 ) . Study objectives included response ( primary ) , survival , toxicity , and quality of life ( QOL ) . RESULTS ORR was 25.0 % ( 95 % CI , 13 % to 41 % ) for ECF , 18.5 % ( 95 % CI , 9 % to 34 % ) for TC , and 36.6 % ( 95 % CI , 23 % to 53 % ) for TCF ( n = 119 ) . Median overall survival times were 8.3 , 11.0 , and 10.4 months for ECF , TC , and TCF , respectively . Toxicity was acceptable , with one toxic death ( TC arm ) . Grade 3 or 4 neutropenia occurred in more treatment cycles with docetaxel ( TC , 49 % ; TCF , 57 % ; ECF , 34 % ) . Global health status/QOL substantially improved with ECF and remained similar to baseline with both docetaxel regimens . CONCLUSION Time to response and ORR favor TCF over TC for further evaluation , particularly in the neoadjuvant setting . A trend towards increased myelosuppression and infectious complications with TCF versus TC or ECF was observed Several chemotherapy regimens used against advanced gastric cancer have been studied extensively over the decades in an attempt to further improve the prognosis of patients . To date , no st and ard chemotherapeutic regimens have been established worldwide . S-1 ( TS-1 ® ) , a combination of ftorafur and two modulators , gimestat ( CDHP ) and oxonic acid , in a molar ratio of 1 : 0.4 : 1 , has been widely used in Japan for the treatment of advanced gastric cancer , and much attention has been paid to attempts to increase its antitumor effect by combining it with other chemotherapeutic drugs . We treated 12 patients with advanced gastric cancer with 80 mg/m2 of S-1 for 21 days and 60 mg/m2 of cisplatin ( CDDP ) on day 8 every 5 weeks . The treatment was continued until disease progression , unacceptable toxicity , or the patient 's refusal . Eight out of 12 evaluable patients achieved a partial response ( PR ) , with a response rate of 66.7 % . The incidence of grade 3 or 4 adverse effects , including myelosuppression and gastrointestinal toxicities , was 16.6 % . None of the patients treated with this regimen died of adverse effects and none required hospitalization for the toxicity . We conclude that the combination of S-1 and CDDP seems to have a high therapeutic index , enhancing the antitumor effect of S-1 while maintaining modest adverse effects , thus suggesting the possible use of this combination based at the outpatient clinic ( apart from a short stay in hospital during the infusion of CDDP with hydration ) . Further study with a large number of patients may be needed to confirm the combination of S-1 and CDDP to be an appropriate first-line chemotherapy for 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 We performed continuous hyperthermic peritoneal perfusion ( CHPP ) or continuous normothermic peritoneal perfusion ( CNPP ) combined with cisplatin ( CDDP ) 300 mg/kg and mitomycin C ( MMC ) 30 mg/kg in an attempt to prevent peritoneal recurrence after surgery for gastric cancer . Twenty-two patients were treated with perfusion  using about 10 liters of saline heated to 41 ° to 42 ° C ( CHPP group ) ;  18 patients were treated with saline heated to 37 ° to 38 ° C ( CNPP group ) ; and 18 patients underwent only gastric surgery without perfusion ( control group ) in a r and omized control study . There were two deaths ( 9 % ) due to peritoneal recurrence in the CHPP group , four ( 22 % ) in the CNPP group , and four ( 22 % ) in the control group . The 1- , 2- , and 3-year survival rates were 95 % , 89 % , and 68 % , in the CHPP group ; 81 % , 75 % , and 51 % , in the CNPP group ; and 43 % , 23 % , and 23 % , in the control group , respectively . There was a significant difference between the three survival curves by the log-rank test ( p<0.01 ) . This difference showed that CNPP and CHPP are both effective procedures for preventing peritoneal recurrence . The maximum concentrations in the perfusate of total and free CDDP with 300 mg administration were 12.2 and 10.1 μg/ml , respectively , at the end of the perfusion , and the maximum concentrations of total and free CDDP in plasma were 2.1 and 1.0 μg/ml , respectively . The maximum concentrations of MMC in perfusate and plasma with 30 mg administration were 1.00 and 0.05 μg/ml , respectively , which are intraperitoneally cytotoxic but systemically safe concentrations . RésuméNous mettons en place une perfusion intrapéritonéale hyper ( PPHC ) ou isothermique continue ( PPNC ) , associée à une chimiothérapie combinée ( cisplatine ( CDDP ) à la posologie de 300 mg/Kg et mitomycine C ( MMC ) à la posologie de 30 mg/Kg ) dans le but de prévenir les récidives péritonéales après chirurgie pour cancer gastrique . Dans une étude r and omisée , 22 patients ont été traités par perfusions péritonéale avec 10 liters de sérum physiologique chauffé à 41–42 ° C ( PPHC ) , 18 ont été traités avec du sérum à 37 ° C ( PPNC ) et 18 ont été opérés de leur cancer gastrique  sans perfusion postopératoire ( groupe contrôle ( 22 % ) ) . Les survies à 1 , 2 et 3 ans étaient de 95 , 89 et 68 % , respectivement dans le groupe PPHC , de 81 , 75 et 51 % dans le groupe PPNC et de 43 , 23 et 23 % dans le groupe contrôle . Les trois courbes de survie différaient de façon significative ( logrank p<0.01 ) . Ces différences montrent que non seulement la perfusion intrapéritonéale associée à la chimiothérapie mais aussi l'hyperthermie intrapéritonéale sont efficaces pour prévenir la récidive péritonéale . après résection gastrique pour cancer . Les concentrations maximales globales et isolées de CDDP  étaient de 12.2 et de 10.1 μg/ml à la fin de la perfusion . Les concentrations plasmatiques maximales de MMC globales et isolées étaient de 1.00 et de 0.05 μg/ml . , respectivement . Ces résultats cliniques favorables démontrent que les concentrations obtenues ainsi ne sont pas nocives . ResumenEn pacientes sometidos a cirugía por cáncer gástrico hemos realizado perfusión peritoneal hipertérmica continua ( PPHC ) o perfusión peritoneal normotérmica continua ( PPNC ) combinada con cisplatino ( CCDP ) en dosis de 300 mg/cuerpo y mitomicina C ( MMC ) en dosis de 30 mg/cuerpo con miras a prevenir la recurrencia peritoneal . Veintidós pacientes fueron tratados con perfusión de alrededor de 10 litros de solución salina calentada a 41–42 ° C ( grupo PPHC ) ; 18 pacientes fueron tratados con solución salina calentada a 37–38 ° C ( grupo PPNC ) ; y 18 pacientes fueron sometidos a cirugía gástrica solamente , sin perfusión , los cuales constituyeron el grupo de control . El estudio fue r and omizado . Las muertes por recurrencias peritoneales fueron dos ( 9 % ) en el grupo PPHC , cuatro ( 22 % ) en el grupo PPNC y cuatro ( 22 % ) en el grupo control . Las tasas de sobrevida a uno , dos y tres años fueron 95 % , 89 % y 68 % en el grupo PPHC ; 81 % , 75 % y 51 % en el grupo PPNC ; y 43 % , 23 % y 23 % en grupo control , respectivamente . Se encontró una diferencia significativa en las tres curvas de sobrevida en la prueba de log-rank ( p<0.01 ) . La significativa diferencia hallada entre las tres curvas de sobrevida demuestran que , no sólo la perfusión intraperitoneal combinada con quimioterapia ( PPNC ) sino también la hipertermia intraperitoneal ( PPHC ) , son procedimientos efectivos para la prevención de la recurrencia peritoneal . Las concentraciones máximas del CCDP total y libre en el líquido de perfusión en el régimen de 300 mg fue 12.2 y 10.1 μg/ml al final de la perfusión . Las máximas concentraciones plasmáticas de CDDP total y libre fueron 2.1 y 1.0 μg/ml al final de la perfusión . Las concentraciones máximas de MMC en el líquido de perfusión y en el plasma en regímenes por debajo de 30 mg fueron 1.0 y 0.05 μg/ml . Tales result ados demuestran concentraciones intraperitoneales citotóxicas pero sistémicamente seguras The majority of advanced gastric carcinoma patients with serosal invasion die of peritoneal recurrence , even when a curative gastrectomy is performed , because peritoneal recurrence occurs due to intraperitoneal free tumor cells that detach from the serosal‐invaded focus . In an attempt to prevent peritoneal recurrence , intraperitoneal hyperthermic chemoperfusion ( IHCP ) treatment was combined with aggressive surgery Objective : This prospect i ve r and omized multicenter study aims to evaluate the efficacy of extensive intraoperative peritoneal lavage followed by intraperitoneal chemotherapy ( EIPL-IPC ) on the overall 5-year survival of advanced gastric cancer patients with intraperitoneal free cancer cells without overt peritoneal metastasis ( CY+/P− ) . The study also aims to determine the merit and reliability of EIPL-IPC therapy as a prophylactic strategy for peritoneal metastasis . Summary Background Data : Although the prognosis of advanced gastric cancer patients with CY+/P− is extremely poor , a suitable st and ard regimen for treating such patients has not yet been established . Methods : A total of 88 patients with CY+/P− from 1522 patients with advanced gastric cancer at multicenters were enrolled in this study and were r and omly allocated to 3 groups : surgery alone group , surgery plus intraperitoneal chemotherapy ( IPC ) group , and surgery plus EIPL and IPC ( EIPL-IPC ) group . Prognostic significance of EIPL-IPC therapy was evaluated by Kaplan-Meier curves , and its value as an independent prognostic factor was assessed by univariate and multivariate analyses . Results : The overall 5-year survival rate of the patients with EIPL-IPC was 43.8 % , and this data were significantly better than that of the IPC group ( 4.6 % , P < 0.0001 ) and the surgery alone group ( 0 % , P < 0.0001 ) . Among various recurrent patterns , the EIPL-IPC group had a significantly lower incidence of peritoneal recurrence than both of the other groups ( P < 0.0001 ) . Univariate and multivariate analyses revealed that EIPL was the most significant impact factor . Conclusions : The present study clearly revealed that EIPL-IPC therapy significantly improved the 5-year survival span of advanced gastric cancer patients with CY+/P−.  Thus , EIPL-IPC therapy is strongly recommended as a st and ard prophylactic strategy for peritoneal dissemination We performed a critical evaluation of neoadjuvant chemotherapy ( NAC ) with TS-1 and cisplatin ( CDDP ) for advanced gastric cancer patients . Since October 2000 , 37 patients with far advanced or non-curative resectable gastric cancer received NAC , together with TS-1 and CDDP  after informed consent was obtained . TS-1 ( 80 mg/m2/day ) was administrated for 21 consecutive days followed by 14 days rest as one course , and CDDP ( 50 mg/m2 ) was infused over 2 hours on day 8 . After at least 2 courses of treatment , the patients underwent  gastrectomy with lymphadenectomy . The median number of courses administered was 3 ( range 2 - 7 ) , and 6 cases were treated on an outpatient basis only . The overall response rate was 62.2 % ( no CR , but 23 PR ) , and the individual response rates were 67.6 % for the primary lesion , 90.5 % for lymph node metastasis including para-aortic region , 50.0 % for liver metastasis and 14.3 % for peritoneal dissemination , respectively . Toxicities were generally mild , no treatment-related death and no serious adverse reactions were observed . There were only 2 grade 4 anemia ( 5.4 % ) , and leucopenia , neutropenia , anemia , thrombocytopenia of grade 3 were observed in one ( 2.7 % ) , 3 ( 8.1 % ) , 6 ( 16.2 % ) , and 2 ( 5.4 % ) patients respectively at hematological toxicity . Appetite loss and diarrhea of grade 3 were observed in only one ( 2.7 % ) patient at nonhematological toxicity . Twenty-four cases had undergone surgical treatment , and resection was performed in all cases . Seventeen of the 24 ( 70.8 % ) patients underwent curative resection . There was no major morbidity following surgery . The patients were favorable both for operation time ( 229 min ) and bleeding volume ( 365 ml ) . The mean duration of hospitalization after surgery was 23.5 days and the only complications were one leakage , ileus and 2 pancreatitis . Two-year survival rate was 46.8 % and MST was 523 days . In conclusion , a combination of TS-1 and CDDP for NAC appears to be an effective treatment modality for far advanced gastric cancer patients in view of toxicities , antitumor effects and QOL of the patients Continuous hyperthermic peritoneal perfusion ( CHPP ) with a solution that contains mitomycin C ( CHPP‐M ) has been clinical ly introduced as a prophylactic treatment for peritoneal recurrence of gastric cancer with serosal invasion . Two studies , each with a treated and a control group , were performed . In the historical control study the postoperative 3‐year survival rate of patients ( 73.7 % ) in the treated group ( n = 38 ) was significantly higher than the survival rate ( 52.7 % ) of those in the control group ( n = 55 ) ( P < 0.04 ) . In the r and om control study the survival rate ( 83 % ) of patients in the treated group ( n = 26 ) was also higher than that ( 67.3 % ) of those in the control group ( n = 21 ) in the 30 months that followed gastric surgery . However , there was no significant difference . In the historical control study with respect to the postoperative complications , anastomotic leak was observed in 8.5 % of patients who were given CHPP‐M and 12.8 % patients who did not have CHPP‐M. In the r and om control study anastomotic leak was observed in 3.1 % of patients who had CHPP‐M and 7.1 % of patients who did not have CHPP‐M. The incidence of adhesive ileus in patients having CHPP‐M did not increase in historical or r and om control groups . Postoperative prolonged intestinal paresis or chemical peritonitis were not induced by CHPP‐M. These results indicate that CHPP‐M is a simple , safe , and readily available prophylactic therapy for peritoneal recurrence that may follow gastric cancer surgery 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 PURPOSE We report the results of a prospect ively r and omized study that compared the combination of epirubicin , cisplatin , and protracted venous-infusion fluorouracil ( PVI 5-FU ) ( ECF ) with the combination of mitomycin , cisplatin , and PVI 5-FU ( MCF ) in previously untreated patients with advanced esophagogastric cancer . PATIENTS AND METHODS Five hundred eighty patients with adenocarcinoma , squamous carcinoma , or undifferentiated carcinoma were r and omized to receive either ECF ( epirubicin 50 mg/m(2 ) every 3 weeks , cisplatin 60 mg/m(2 ) every 3 weeks and PVI 5-FU 200 mg/m(2)/d ) or MCF ( mitomycin 7 mg/m(2 ) every 6 weeks , cisplatin 60 mg/m(2 ) every 3 weeks , and PVI 5-FU 300 mg/m(2)/d ) and analyzed for survival , response , toxicity , and quality of life ( QOL ) . RESULTS The overall response rate was 42.4 % ( 95 % confidence interval [ CI ] , 37 % to 48 % ) with ECF and 44.1 % ( 95 % CI , 38 % to 50 % ) with MCF ( P = .692 ) . Toxicity was tolerable , and there were only two toxic deaths .  ECF result ed in more grade 3/4 neutropenia and grade 2 alopecia , but MCF caused more thrombocytopenia and plantar-palmar erythema . Median survival was 9.4 months with ECF and 8.7 months with MCF ( P = .315 ) ; at 1 year , 40.2 % ( 95 % CI , 34 % to 46 % ) of ECF and 32.7 % ( 95 % CI , 27 % to 38 % ) of MCF patients were alive . Median failure-free survival was 7 months with both regimens . Global QOL scores were better with ECF at 3 and 6 months . CONCLUSION This study confirms response , survival , and QOL benefits of ECF observed in a previous r and omized study . The equivalent efficacy of MCF was demonstrated , but QOL was superior with ECF . ECF remains one of the reference treatments for advanced esophagogastric cancer
INTRODUCTION An important component of treatment failure in gastric cancer ( GC ) is cancer dissemination within the peritoneal cavity and nodal metastasis .
Intraperitoneal chemotherapy ( IPC ) is considered to give a fundamental contribute in treating advanced GC .
The purpose of the study is to investigate the effects of IPC in patients with advanced GC .