Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colon cancer at high risk of peritoneal carcinomatosis; the COLOPEC randomized multicentre trial The Role of Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy (CRS/HIPEC) in Patients with High-Grade Appendiceal Carcinoma and Extensive Peritoneal Carcinomatosis Impact of maximal cytoreductive surgery plus regional heated intraperitoneal chemotherapy (HIPEC) on outcome of patients with peritoneal carcinomatosis of gastric origin: results of the GYMSSA trial. Effects of Intraperitoneal Chemotherapy with Mitomycin C on the Prevention of Peritoneal Recurrence in Colorectal Cancer Patients with Positive Peritoneal Lavage Cytology Findings Use of archived specimens in evaluation of prognostic and predictive biomarkers. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. Combined intravenous and intraperitoneal chemotherapy with fluorouracil + leucovorin vs fluorouracil + levamisole for adjuvant therapy of resected colon carcinoma. Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses. Adjuvant regional chemotherapy and systemic chemotherapy versus systemic chemotherapy alone in patients with stage II-III colorectal cancer: a multicentre randomised controlled phase III trial. Phase II trial of adjuvant radiation and intraperitoneal 5-fluorouracil for locally advanced colon cancer: results with 10-year follow-up. Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: a pooled analysis of north central cancer treatment group phase III trials N9741 and N9841. Whole-body hyperthermia combined with hyperthermic intraperitoneal chemotherapy for the treatment of stage IV advanced gastric cancer Prospective randomized trial of intravenous v intraperitoneal 5-FU in patients with advanced primary colon or rectal cancer. Adjuvant intraperitoneal 5-fluorouracil in high-risk colon cancer: A multicenter phase III trial.
Background The peritoneum is the second most common site of recurrence in colorectal cancer . Early detection of peritoneal carcinomatosis ( PC ) by imaging is difficult . Patients eventually presenting with clinical ly apparent PC have a poor prognosis . Median survival is only about five months if untreated and the benefit of palliative systemic chemotherapy is limited . Only a quarter of patients are eligible for curative treatment , consisting of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy ( CR/HIPEC ) . However , the effectiveness depends highly on the extent of disease and the treatment is associated with a considerable complication rate . These clinical problems underline the need for effective adjuvant therapy in high-risk patients to minimize the risk of outgrowth of peritoneal micro metastases . Adjuvant hyperthermic intraperitoneal chemotherapy ( HIPEC ) seems to be suitable for this purpose . Without the need for cytoreductive surgery , adjuvant HIPEC can be performed with a low complication rate and short hospital stay . Methods / Design The aim of this study is to determine the effectiveness of  adjuvant HIPEC  in preventing the development of PC in patients with colon cancer at high risk of peritoneal recurrence . This study will be performed in the nine Dutch HIPEC centres , starting in April 2015 . Eligible for inclusion are patients who underwent curative resection for T4 or intra-abdominally perforated cM0 stage colon cancer . After resection of the primary tumour , 176 patients will be r and omized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm , or to systemic chemotherapy only in the control arm . Adjuvant HIPEC will be performed simultaneously or shortly after the primary resection . Oxaliplatin will be used as chemotherapeutic agent , for 30 min at 42 - 43 ° C . Just before HIPEC , 5-fluorouracil and leucovorin will be administered intravenously . Primary endpoint is peritoneal disease-free survival at 18 months . Diagnostic laparoscopy will be performed routinely after 18 months postoperatively in both arms of the study in patients without evidence of disease based on routine follow-up using CT imaging and CEA . Discussion Adjuvant HIPEC is assumed to reduce the expected 25 % absolute risk of PC in patients with T4 or perforated colon cancer to a risk of 10 % . This reduction is likely to translate into a prolonged overall survival . Trial registration numberNCT02231086 ( Clinical trials.gov Background Patients with peritoneal mucinous carcinomatosis ( PMCA ) of appendiceal origin and extensive disease are commonly advised against CRS/HIPEC . We hypothesize that CRS/HIPEC is a beneficial treatment for this group . Methods Retrospective analysis of 134 patients with appendiceal cancer treated with CRS/HIPEC was performed from a prospect i ve data base . Extent of disease , measured by peritoneal cancer index ( PCI ) , was related to completeness of cytoreduction ( CC ) , lymph node ( LN ) status , and prior surgery score ( PSS ) . Overall survival ( OS ) was estimated by Kaplan-Meier curves . Test differences were calculated using log-rank test . Results A total of 77 patients ( 57 % ) had PMCA . Mean follow-up was 22 months with a median of 18 months . OS was 88 % , 56 % , and 40 % for 1 , 3 , and 5 years , respectively . 68 % had PCI ≥ 20 . LN metastasis was found in 44 % of patients in PCI ≥ 20 and PCI < 20 groups . 73 % and 60 % of patients had PSS of 2 or 3 in PCI ≥ 20 and PCI < 20 groups , respectively ( P = .196 ) . Complete cytoreduction was achieved in 65 % of PCI ≥ 20 group and 96 % of PCI < 20 group ( P = .004 ) . With complete cytoreduction , the 5-year OS was 45 % in PCI ≥ 20 group and 66 % in PCI < 20 group ( P = .139 ) . 18 of 19 patients with incomplete cytoreduction had PCI ≥ 20 , with 3- and 5-year OS of 27 % and 0 % . Hazard ratios ( by Cox regression ) were 2.8 ( 95 % confidence interval [ 95 % CI ] 0.8–10.2 ) and 3.6 ( 95 % CI 1.5–8.8 ) for PCI < 20 and complete cytoreduction , respectively . Conclusions Meaningful long-term survival could be achieved in patients with PMCA even with extensive peritoneal disease . PCI ≥ 20 should not be used as an exclusion criterion when selecting these patients for CRS/HIPEC , and every effort should be made to achieve complete cytoreduction BACKGROUND A prospect i ve r and omized trial was conducted to compare the impact of systemic chemotherapy versus multi-modality therapy ( complete cytoreductive surgery ( CRS ) , hyperthermic intraperitoneal chemotherapy ( HIPEC ) , and systemic chemotherapy ) on overall survival ( OS ) in patients with gastric carcinomatosis . METHODS Patients with measurable metastatic gastric adenocarcinoma involving the peritoneum , and resectable to " no evidence of disease " were r and omized to gastrectomy , metastasectomy , HIPEC , and systemic FOLFOXIRI ( GYMS arm ) or FOLFOXIRI alone ( SA arm ) . RESULTS Seventeen patients were enrolled ( 16 evaluable ) ; 7 of 9 patients in the multi-modality GYMS arm achieved complete cytoreduction ( CCR0 ) . Median OS was 11.3 months in the GYMS arm and 4.3 months in the SA arm . Four patients in the GYMS arm survived > 12 months , 2 patients close to 2 years at last follow-up , and 1 patient more than 4 years , with 2 of these patients still alive . No patient in the SA arm lived beyond 11 months . All patients surviving beyond 12 months in the surgery arm achieved complete cytoreduction and had an initial Peritoneal Cancer Index ( PCI ) of ≤ 15 . CONCLUSION Maximal cytoreductive surgery combined with regional ( HIPEC ) and systemic chemotherapy in selected patients with gastric carcinomatosis and limited disease burden can achieve prolonged survival Background The detection of intraperitoneal free cancer cells in colorectal cancer ( CRC ) patients is associated with a poorer prognosis . The aim of this study was to investigate the effects of intraperitoneal chemotherapy ( IPC ) with mitomycin C ( MMC ) on preventing peritoneal recurrence in CRC patients with positive peritoneal lavage cytology findings . Methods A total of 52 CRC patients who had no clinical ly confirmed peritoneal dissemination and whose status of peritoneal lavage cytology was positive were investigated . Conventional peritoneal lavage cytology was performed . Overall , 31 of the 52 patients ( 59.6 % ) were administered IPC with MMC . Before closure of the abdomen , 4 silicon catheters were inserted into peritoneal cavity . After closure , the perfusate ( diluting 20 mg MMC with 500 ml saline ) was instilled from the catheter , and all catheters were clumped . All catheters were opened 1 h later . Results The mean follow-up period was 83.1 months . According to univariate analyses of all 52 patients and the subgroup of 36 patients with stage II or III tumors , patients with IPC  had a significantly better peritoneal recurrence-free survival and cancer-specific survival than patients who did not receive IPC  ( P < 0.005 ) . In multivariate analysis , IPC remained an independent prognostic factor for peritoneal recurrence-free survival in all patients . Conclusions It appears that IPC with MMC is an effective treatment to prevent peritoneal recurrence and prolong the cancer-specific survival in CRC patients without peritoneal dissemination , but who have positive peritoneal lavage cytology . It is necessary to verify the effectiveness of IPC with MMC in a prospect i ve trial The development of tumor biomarkers ready for clinical use is complex . We propose a refined system for biomarker study design , conduct , analysis , and evaluation that incorporates a hierarchal level of evidence scale for tumor marker studies , including those using archived specimens . Although fully prospect i ve r and omized clinical trials to evaluate the medical utility of a prognostic or predictive biomarker are the gold st and ard , such trials are costly , so we discuss more efficient indirect " prospect ive-retrospective " design s using archived specimens . In particular , we propose new guidelines that stipulate that 1 ) adequate amounts of archived tissue must be available from enough patients from a prospect i ve trial ( which for predictive factors should generally be a r and omized design ) for analyses to have adequate statistical power and for the patients included in the evaluation to be clearly representative of the patients in the trial ; 2 ) the test should be analytically and preanalytically vali date d for use with archived tissue ; 3 ) the plan for biomarker evaluation should be completely specified in writing before the performance of biomarker assays on archived tissue and should be focused on evaluation of a single completely defined classifier ; and 4 ) the results from archived specimens should be vali date d using specimens from one or more similar , but separate , studies BACKGROUND St and ard chemotherapy for newly diagnosed ovarian cancer is a platinum-taxane combination . The Gynecologic Oncology Group conducted a r and omized , phase 3 trial that compared intravenous paclitaxel plus cisplatin with intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel in patients with stage III ovarian cancer . METHODS We r and omly assigned patients with stage III ovarian carcinoma or primary peritoneal carcinoma with no residual mass greater than 1.0 cm to receive 135 mg of intravenous paclitaxel per square meter of body-surface area over a 24-hour period followed by either 75 mg of intravenous cisplatin per square meter on day 2 ( intravenous-therapy group ) or 100 mg of intraperitoneal cisplatin per square meter on day 2 and 60 mg of intraperitoneal paclitaxel per square meter on day 8 ( intraperitoneal-therapy group ) . Treatment was given every three weeks for six cycles . Quality of life was assessed . RESULTS Of 429 patients who underwent r and omization , 415 were eligible .  Grade 3 and 4 pain , fatigue , and hematologic , gastrointestinal , metabolic , and neurologic toxic effects were more common in the intraperitoneal-therapy group than in the intravenous-therapy group ( P < or = 0.001 ) . Only 42 percent of the patients in the intraperitoneal-therapy group completed six cycles of the assigned therapy , but the median duration of progression-free survival in the intravenous-therapy and intraperitoneal-therapy groups was 18.3 and 23.8 months , respectively ( P=0.05 by the log-rank test ) . The median duration of overall survival in the intravenous-therapy and intraperitoneal-therapy groups was 49.7 and 65.6 months , respectively ( P=0.03 by the log-rank test ) . Quality of life was significantly worse in the intraperitoneal-therapy group before cycle 4 and three to six weeks after treatment but not one year after treatment . CONCLUSIONS As compared with intravenous paclitaxel plus cisplatin , intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel improves survival in patients with optimally debulked stage III ovarian cancer Adjuvant chemotherapy with fluorouracil ( FU ) and levamisole or FU/leucovorin ( LV ) has been established as effective adjuvant treatment for patients with stage III colon cancer . Among several other promising treatment strategies in resected colon cancer , intraperitoneal anti-cancer drug administration with its appealing rationale of counteracting microscopic residual disease on peritoneal surfaces and occult metachronous liver metastases by achieving high intraportal drug concentrations has not yet undergone sufficient clinical evaluation . To determine whether a combination of this locoregional therapeutic concept with systemic intravenous administration of FU/LV would yield better results than conventional adjuvant chemoimmunotherapy with FU/levamisole , the present r and omized study was initiated . A total of 241 patients with resected stage III or high-risk stage II ( T4N0M0 ) colon cancer were r and omly assigned to ' st and ard therapy ' with FU and levamisole , given for a duration of 6 months , or to an investigational arm , consisting of LV 200 mg m(-2 ) plus FU 350 mg m(-2 ) , both administered intravenously ( days 1 - 4 ) and intraperitoneally ( days 1 and 3 ) every 4 weeks for a total of six courses . In patients with stage II disease , no significant difference was noted between the two arms after a median follow-up time of 4 years ( range 2.5 - 6 years ) . Among 196 eligible patients with stage III disease , however , a comparative analysis of the two treatment groups suggested both an improvement in disease-free survival ( P = 0.0014 ) and a survival advantage ( P = 0.0005 ) , with an estimated 43 % reduction in mortality rate ( 95 % confidence interval 26 - 70 % ) in favour of the investigational arm . In agreement with its theoretical rationale , combined intraperitoneal and intravenous FU/LV was particularly effective in reducing locoregional tumour recurrences with or without liver or other organ site involvement ( 9 vs 25 patients in the FU/levamisole arm ; P = 0.005 ) . Treatment-associated side-effects were infrequent and generally mild in both arms , although a lower rate of severe ( WHO grade 3 ) adverse reactions was noted in patients receiving locoregional plus intravenous chemotherapy ( 3 % vs 12 % ; P = 0.01 ) . The results of this trial suggest that combined intraperitoneal plus systemic intravenous chemotherapy with FU/LV is a promising adjuvant treatment strategy in patients with surgically resected stage III colon carcinoma PURPOSE The National Surgical Adjuvant Breast and Bowel Project ( NSABP ) C-07 trial demonstrated that the addition of oxaliplatin to fluorouracil plus leucovorin ( FULV ) improved disease-free survival ( DFS ) in patients with stage II or III colon cancer . This analysis is the first publication of overall survival ( OS ) for the NSABP C-07 study . We up date d DFS and examined both end points in clinical ly relevant patient subsets . PATIENTS AND METHODS Other studies have identified patients age 70 or older and those with stage II disease as patient subsets in which oxaliplatin may not be effective . We investigated toxicity as a driver of divergent outcomes in these subsets . RESULTS In all , 2,409 eligible patients with follow-up were r and omly assigned to either FULV ( FU 500 mg/m(2 ) by intravenous [ IV ] bolus weekly for 6 weeks ; leucovorin 500 mg/m(2 ) IV weekly for 6 weeks of each 8-week cycle for three cycles ) or FLOX ( FULV plus oxaliplatin 85 mg/m(2 ) IV on days 1 , 15 , and 29 of each cycle ) . With 8 years median follow-up , OS was similar between treatment groups ( hazard ratio [ HR ] , 0.88 ; 95 % CI , 0.75 to 1.02 ; P = .08 ) . FLOX remained superior for DFS ( HR , 0.82 ; 95 % CI , 0.72 to 0.93 ; P = .002 ) . The effect of oxaliplatin on OS did not differ by stage of disease ( interaction P = .38 for OS ; interaction P = 0.37 for DFS ) but did vary by age for OS ( younger than age 70 v 70 + interaction P = .039 ) . There was a similar trend for DFS ( interaction P = .073 ) . Oxaliplatin significantly improved OS in patients younger than age 70 ( HR , 0.80 ; 95 % CI , 0.68 to 0.95 ; P = .013 ) , but no positive effect was evident in older patients . CONCLUSION Overall , the addition of oxaliplatin to FULV has not been proven to extend OS in this trial , but the DFS effect remained strong . Unplanned subset analyses suggest a significant OS effect of oxaliplatin in patients younger than age 70 BACKGROUND Systemic adjuvant chemotherapy can improve overall survival and reduce the incidence of distant metastases for patients with advanced colon cancer . This study aim ed to investigate whether regional chemotherapy ( given by intraperitoneal or intraportal methods ) combined with systemic chemotherapy was more effective than was systemic chemotherapy alone in terms of survival and recurrence for patients with stage II-III colorectal cancer . The study also compared systemic chemotherapy with fluorouracil and folinic acid with that of fluorouracil and levamisole . METHODS During surgery , 753 patients with stage II-III colorectal cancer were r and omly assigned to systemic chemotherapy alone ( 379 with fluorouracil and folinic acid , and 374 with fluorouracil and levamisole ) , and 748 to postoperative regional chemotherapy with fluorouracil followed by systemic chemotherapy with fluorouracil and folinic acid ( n=368 ) or with fluorouracil and levamisole ( n=380 ) . Regional chemotherapy was given intraperitoneally ( n=415 ) or intraportally ( n=235 ) according to institution . The primary endpoint was 5-year overall survival . Secondary endpoints were 5-year disease-free survival and toxic effects . Analyses were by intention to treat . FINDINGS Median follow-up was 6.8 years ( range 0.0 - 10.1 ) . 5-year overall survival was 72.3 % ( 95 % CI 69.0 - 75.6 ) for patients assigned regional and systemic chemotherapy , compared with 72.0 % ( 68.7 - 75.3 ) for those assigned systemic chemotherapy alone ( hazard ratio [ HR ] 0.97 [ 0.81 - 1.15 ] , p=0.69 ) . 5-year overall survival for all patients assigned fluorouracil and levamisole was 72.0 % ( 68.7 - 75.2 ) compared with 72.3 % ( 69.0 - 75.6 ) for all those assigned fluorouracil and folinic acid ( HR 0.98 [ 0.82 - 1.17 ] , p=0.81 ) . The hazard ratios for 5-year disease-free survival were 0.94 ( 0.80 - 1.10 ) for regional versus non-regional treatment , and 0.92 ( 0.79 - 1.08 ) for all fluorouracil and levamisole versus fluorouracil and folinic acid .  Grade 3 - 4 toxic effects were low in all groups . INTERPRETATION Fluorouracil-based regional chemotherapy adds no further benefit to that obtained with systemic chemotherapy alone in patients with advanced colorectal cancer PURPOSE To determine the toxicity , disease-free survival , and overall survival for patients with Modified Astler-Coller ( MAC ) B2 - 3 or C1 - 3 colon cancer receiving adjuvant radiation and sequential intraperitoneal 5-fluorouracil ( 5-FU ) .  METHODS AND MATERIAL S From August 1984 to June 1989 , 45 patients were accrued to this Phase II trial and received a 21-week course of intraperitoneal 5-FU ( 20 mg/kg/d x 5 ) and external beam radiation . The radiation was delivered to the tumor bed and para-aortic lymph nodes in two split-courses of 22.5 Gy , alternating with the first two cycles of chemotherapy . All patients then received 4 additional cycles of intraperitoneal 5-FU . RESULTS The therapy was well tolerated with 4 patients experiencing Grade 3 peritonitis . Four patients developed small bowel obstruction requiring surgery ; in each instance , recurrent tumor was found at the time of laparotomy . The median and overall survivals at 10 years were 9.3 months and 53 % respectively . Local failures were infrequent , occurring in only 11 % of patients treated . CONCLUSIONS Sequential intraperitoneal 5-FU and tumor-bed/para-aortic irradiation is tolerable in patients with resected colon cancer . Although the incidence of local and regional relapse appeared to be lower than anticipated , this did not appear to translate into improved survival PURPOSE Symptoms and complications of metastatic colorectal cancer ( mCRC ) differ by metastatic sites . There is a paucity of prospect i ve survival data for patients with peritoneal carcinomatosis colorectal cancer ( pcCRC ) . We characterized outcomes of patients with pcCRC enrolled onto two prospect i ve r and omized trials of  chemotherapy and contrasted that with other manifestations of mCRC ( non-pcCRC ) . METHODS A total of 2,095 patients enrolled onto two prospect i ve r and omized trials were evaluated for  overall survival ( OS ) and progression-free survival ( PFS ) . A Cox proportional hazard model was used to assess the adjusted associations . RESULTS The characteristics of the pcCRC group ( n = 364 ) were similar to those of the non-pcCRC patients in median age ( 63 v 61 years , P = .23 ) , sex ( 57 % males v 61 % , P = .23 ) , and performance status ( Eastern Cooperative Oncology Group performance status 0 or 1 94 % v 96 % , P = .06 ) , but differed in frequency of liver ( 63 % v 82 % , P < .001 ) and lung metastases ( 27 % v 34 % , P = .01 ) . Median OS ( 12.7 v 17.6 months , hazard ratio [ HR ] = 1.3 ; 95 % CI , 1.2 to 1.5 ; P < .001 ) and PFS ( 5.8 v 7.2 months , HR = 1.2 ; 95 % CI , 1.1 to 1.3 ; P = .001 ) were shorter for pcCRC versus non-pcCRC . The unfavorable prognostic influence of pcCRC remained after adjusting for age , PS , liver metastases , and other factors ( OS : HR = 1.3 , P < .001 ; PFS : HR = 1.1 , P = .02 ) . Infusional fluorouracil , leucovorin , and oxaliplatin was superior to irinotecan , leucovorin , and fluorouracil as a first-line treatment among pcCRC ( HR for OS = 0.62 , P = .005 ) and non-pcCRC patients ( HR = 0.66 , P < .001 ) . CONCLUSION pcCRC is associated with a significantly shorter OS and PFS as compared with other manifestations of mCRC . Future trials for mCRC should consider stratifying on the basis of pcCRC status Background : Currently known as a metastatic disease , stage IV gastric cancer can not be cured by surgery , but treatments are recommended to relieve symptoms such as pain and to prolong survival . Methods : With better access to metastases and certain large or inoperable tumours , we applied two treatment sessions of combined therapy of whole-body hyperthermia and hyperthermic intraperitoneal chemo-perfusion in the treatment group , while patients in the control group were treated with oxaliplatin combined with 5-fluorouracil chemotherapy or Xeloda . We used the RECIST criteria for outcome evaluation . Results : With the combined treatment , we found the complete and partial remission rate of patients to be 61.5 % , and the rate of stable disease was 19.2 % . Symptoms such as pain and a large volume of ascites were alleviated , and the quality of life was correspondingly improved . In addition , the combined treatment had a significant therapeutic benefit against the primary tumour and the metastases to the lymph nodes and liver . Survival time was also significantly prolonged ( the 1-year survival rate was 38.5 % compared to the control group rate of 19 % ) . Conclusions : These results suggest that whole-body hyperthermia combined with hyperthermic intraperitoneal chemotherapy is an effective treatment for patients with advanced gastric malignancies No new chemotherapy agents have been developed in the recent past that present hope for improving survival in patients with colon or rectal cancer . This study was undertaken to investigate a new route of administering an old drug , 5-fluorouracil ( 5-FU ) . When 5-FU is delivered by the intraperitoneal ( IP ) route the tolerable dose of drug was markedly increased without an increase in adverse side effects . The natural history of surgically treated disease was changed by reducing the incidence of peritoneal carcinomatosis , but time to relapse and survival was not improved . Intraperitoneal 5-FU may be recommended for investigation in patients with perforated colon cancer , peritoneal implants , or as one part of a multimodality treatment protocol for colorectal cancer . If 5-FU is given to patients with gastrointestinal malignancy , the IP route should be strongly considered OBJECTIVE To evaluate the results of a prospect i ve multicenter r and omized study of adjuvant intraperitoneal 5-fluorouracil ( 5-FU ) administered during 6 days shortly after resection of stages II and III colon cancers . SUMMARY BACKGROUND DATA Systemic adjuvant chemotherapy improves the survival of patients with stage III colon cancer receiving treatment for 6 months . Intraperitoneal chemotherapy theoretically combines peritoneal and hepatic effects . METHODS After resection , 267 patients were r and omized into two groups . Patients in group 1 ( n = 133 ) underwent resection followed by intraperitoneal administration of 5-FU ( 0.6 g/m2/day ) for 6 days ( day 4 to day 10 ) . These patients also received intravenous 5-FU ( 1 g ) during surgery . Patients in group 2 underwent resection alone ( n = 134 ) . RESULTS In group 1 , 103 patients received the total dose , 18 received a partial dose as a result of technical or tolerance problems , and 12 did not receive the chemotherapy .  Rates of surgical death and complications were similar in both groups . Tolerance to treatment was excellent or fair in 97 % of the patients and poor in 3 % . After a median follow-up of 58 months , 5-year overall survival rates were 74 % in group 1 and 69 % in group 2 ; disease-free survival rates were 68 % and 62 % , respectively . Survival curves were superimposed until 3 years after treatment and began diverging thereafter . Among patients receiving the full treatment , the 5-year disease-free survival rate was improved in the treatment group in patients with stage II cancers but was unchanged in patients with stage III cancers . CONCLUSIONS Chemotherapy with intraperitoneal 5-FU administered during a short period after surgery was well tolerated but was not sufficient to reduce the risk of death significantly . However , it reduced the risk of recurrence in stage II cancers . These results suggest that it should be associated with systemic chemotherapy to reduce both local and distant recurrences
Abstract Background : The peritoneal surface is the second most common site of disease recurrence , after the liver , following definitive surgery for colorectal cancer .
Adjuvant intraperitoneal ( IP ) chemotherapy delivered at time of surgical resection has the potential to delay or prevent future spread to the peritoneal surface and improve clinical outcome .
The exact role of adjuvant IP chemotherapy in colorectal cancer , including its associated morbidity and mortality , is not well defined .