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Clinical research of continuous hyperthermic intraperitoneal perfusion chemotherapy combining with intravenous chemotherapy to treat advanced gastrointestinal tumors

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2019/07/16
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Clinical research of continuous hyperthermic intraperitoneal perfusion chemotherapy combining with intravenous chemotherapy to treat advanced gastrointestinal tumors
 
Yanjie Zhao , Ruibin Wang , Shifeng Qiao
 
[Abstract] Objective : In order to explore an effective treatment for advanced gastrointestinal tumors , Clinical studies and preliminary efficacy evaluation were performed in continuous hyperthermic intraperitoneal perfusion chemotherapy(Hyperthermic intraperitoneal chemoperfusion , HIPC) , intraperitoneal chemotherapy and simple intravenous chemotherapy . Methods : A retrospective analysis of 53 patients with advanced gastrointestinal tumors , admitted from September , 1999 to October , 2003 , was performed . The patients received HIPC+intravenous chemotherapy(HIPC+IVC,14 cases) , simple intravenous chemotherapy(SIVC,21cases)and conventional intraperitoneal chemotherapy+intravenous chemotherapy(IPC+IVC,18 cases)for more than 2 courses,respectively . The difference of efficacies was analyzed . Results : there were significant differences in the recession rates and total efficacies between HIPC+IVC group and HIPC+IVC group or SIVC group(P<0.05) , and HIPC+IVC had significant advantage in the treatment of metastatic ascites(P<0.05) , but the advantage of lessening hepatic metastases cannot be affirmed(P>0.05) . The therapy caused smaller systemic side effects than SIVC and more weakly harmed the immune system of the body . The patients in HIPC+IVC group significantly improved the quality of life , and had higher clinical benefit rate . Conclusion : For patients with advanced gastrointestinal tumors , HIPC+IVC has better efficacy , less side effects , fewer days of hospitalization , lower average hospitalization fee and higher benefit/investment . 
[Key words] Gastrointestinal tumors , intraperitoneal chemotherapy , hyperthermic perfusion , intravenous chemotherapy
 
  Gastrointestinal cancer is a main malignant tumor to threat the health of the people in our country . According to statistics from Ministry of Health , the annual mortality rate of only gastric cancer in China in 90s reached 2521/100,000[1] , representing the first among malignant tumors . Currently the treatment of gastrointestinal tumors mainly is surgical radical excision , but for patients with cancer metastasis in moderate and advanced stage , because gastrointestinal venous blood returns to the portal vein system , cancer cells are easily transferred to the liver through the portal vein . When primary tumor invades the whole layer of serosa or lymph node metastasis invades the whole layer of the capsule,tumor cells shed , adhere and are planted on the peritoneum , and invade interstitial tissue and reproduce , leading to intraperitoneal recurrence and metastasis . Clinical observations indicate that most patients with gastrointestinal tumors have died of intraperitoneal or hepatic metastases . Literature has reported that after gastric cancer radical operations 5-year survival rate is only 39%to 45% , postoperative resection site recurrence rate is 60-90%,peritoneal metastasis rate is up to 50%and hepatic metastasis rate is 30% . For such patients , through intravenous chemotherapy the drug concentration in a focus is limited . If the concentration of chemotherapeutic drugs is simply increased , systemic toxic and side effects will correspondingly increase thus the efficacy of high-dose intravenous chemotherapy is often not ideal . In the past , we often used IPC+IVC treatment ; although the efficacy was improved to some extent , the incidence of chemical peritonitis was high and abdominal local side effects were large . In recent years , the academic community has put forward an opinion that HIPC+IVC can effectively prevent and treat intraperitoneal recurrence and hepatic metastasis after operations of gastrointestinal tumors[2,3] , and can improve the quality of life of the patients[4].We used the continuous perfusion machine to perform HIPC+IVC treatment in patients and have specifically observed its effect .
 
Materials and Methods
1.General information : 53 patients with advanced gastrointestinal tumors were admitted from September , 1999 to October , including 34 males and 19males . The median age was 50.5 years(32 to 69 years) . Specific grouping is shown in Table 1 and metastases of patients in each group are showed in Table 2 .
  2.Short-term efficacy was evaluated according to WHO uniform criteria[5].(1)Complete remission(CR) : A visible tumor completely disappeared and the state had lasted for more than 1 month;(2)Partial remission(PR) : The product of the two largest diameters of the tumor which is perpendicular to each other decreased by more than 50%,and the state had lasted for more than 1 month ; (3)Stable disease(SD) : The product of the two largest diameters of the tumor which is perpendicular to each other decreased by less than 50%or increased by less than 25% , and the state had lasted for more than 1 month ; (4)Progressive disease(PD) : The product of the two largest diameters of the tumor which is perpendicular to each other increased by more than 25%.
 
  3 . Adverse reactions were evaluated according to WHO criteria in 1981[5].
 
  4 . Treatment methods:
 
  (1)HIPC+IVC group specific treatment regimen : IVC used fluorouracil(5-FU)300 mg/m2 which was intravenously infused ; day 1 to day 5,calcium folinate(CF)100 mg/m2 was intravenously infused 2 hours before 5-FU had been administered . One course lasted for 21 days . HIPC was performed weekly . RHL-2000 perfusion machine was used to circularly perfuse 2000-2500ml of hyperthermic physiological saline at 44℃ , cisplatin(DDP)40 mg/m2 , 5-FU 500 mg/m2 , dexamethasone 10mg and gentamicin 160,000 U . The whole perfusion process lasted for more than two hours . At the inlet and outlet there were strict temperature control devices . At the outlet the temperature was controlled at 41℃and at the inlet the temperature was controlled at 44℃ . If WBC was<4.0×109/L or platelets was<80×109/L , chemotherapy might be delayed until blood returned to normal , and then the next chemotherapy began .
 
  (2)SIVC group specific chemotherapy regimen : 5-FU 500mg/m2 was intravenously infused ; day 1 to day 5 , CF 200mg/m2 was intravenously infused 2 hours before 5-FU had been administered ; day 1 and day 3 , DDP 30mg/m2 was intravenously infused . One course lasted for 21 days .
 
  (3)Intravenous chemotherapy and intraperitoneal chemotherapy of IPC+IVC group were the same as those of HIPC+IVC group , and the difference is that IPC+IVC did not perform hyperthermic perfusion .
 
  5.Statistical analysis : Exact probability and Ridit analysis were used to compare efficacies between two groups . P&lt ; 0.05 showed that the difference was statistically significant .
 
  Results
 
  1.Comparison of efficacies : see Table 3 . The difference between remission rates of HIPC+IVC group and SIVC group was statistically significant(P<0.05) . The difference between remission rates of HIPC+IVC group and IPC+IVC group was not statistically significant(P>0.05) . Ridit analysis was performed for HIPC+IVC group and SIVC group,HIPC+IVC group and IPC+IVC group,respectively,P<0.05,indicating that in the total efficacy , HIPC+IVC group has significant advantage,compared to the other two groups .
 
  2.Comparison of efficacies of three therapies for hepatic metastases : see Table 4.Comparing HIPC+IVC group with SIVC or with IPC+IVC group,respectively , the difference was not significant(P>0.05) .  
 
3.Comparison of efficacies of three therapies for metastatic ascites : see Table 5.Comparing HIPC+IVC group with SIVC group,the difference was significant(P<0.05) . Comparing HIPC+IVC group with IPC+IVC group , the difference was not significant(P>0.05) .
 
4.Improvement of the quality of life of the patients of the three groups:KPS scores of the three groups of patients before treatment and after two courses of treatment were compared[6](asymptomatic free activity was evaluated as 100 points , symptomatic free activity was 90,lying in bed&lt ; 50%was 60-80,lying in bed&gt ; 50%was 40-60 and completely lying in bed was 10-40) . After treatment,compared with the score before treatment , increasing more than 20 points was regarded as significant improvement , increasing 10-19 was improvement , increasing or decreasing less than 10 was stabilization , and decreasing more than 10 was decline . Specific data of the three groups was shown in Table 6 .
 
 
5.Toxic and side reactions : the patients of the three groups had mild toxic and side reactions , mainly including gastrointestinal reactions and bone marrow suppression(see Table 7) .
 
6.Comparison of economic benefit:see Table 8.
 
Discussion
  Hyperthermia selectively harms tumor tissue because compared with normal tissue cells tumor tissue cells has different thermal tolerance[7] . Due to anatomical structural difference between tumor tissue and normal tissue , blood flow in tumor tissue is larger than normal tissue , and heat dissipation is difficult . Heating causes further hypoxia of tumor tissue,decrease of pH value,and inadequate nutrition , thus damages tumor tissue cells . Normal tissue cells can tolerate 47℃of hyperthermia for 1 hour , while at 43℃for 1 hour irreversible impairment of tumor tissue cells emerges . Moreover , HIPC increases permeability of tumor cell membrane , and increases the response rate of cells to drugs[8] . In addition , chemotherapy drugs have a synergistic effect with hyperthermic therapy to enhance killing effect on tumor cells , and heating also can inhibit repair of tumor cells after the chemotherapy[9] . Large-capacity hyperthermic perfusion can still reduce the stimulating effect of chemotherapy drugs on peritoneum to reduce sclerosing peritonitis incidence to some extent .
  HIPC may exert certain effect on reversing multidrug resistance of tumor cells . We have performed animal experiments . The experimental animals were randomly divided into two groups . One group received IPC and another group received HIPC . The results showed that the concentration of chemotherapeutic drugs in tumor cells of the animals in HIPC group was higher than IPC group , indicating that HIPC may reverse multidrug resistance of tumor cells to some extent . However , it still needs further experimental studies .
  While HIPC+IVC improves the efficacy and the quality of life , reduces the economic pressure of the patients . Because HIPC+IVC has small systemic side effects , it reduces the economic pressure of the patients caused by the support treatment , reduces probability of using WBC colony stimulating factor , erythropoietin , etc. , reduces the number of blood transfusions , and shortens hospital stay of the patients.Therefore , it reduces the patients ’ hospitalization fee and greatly reduces the economic burden on the patients .
  About efficacy of hepatic metastases,because our study sample size is too small , statistical significance is not large . Meanwhile , this is a hot topic discussed in the current academic community and sample needs to be accumulated for further study . 
  HIPC+IVC efficacy is certain and its systemic toxic and side effects are small . However , because the chemotherapy drugs directly contact with the abdominal cavity , possibility of chemical peritonitis and intestinal obstruction caused by the method is still larger than SIVC though it is smaller than IPC+IVC . The research on this aspect should be intensified to allow HIPC to be better applied in clinical practice .
 
References
1 Chinese Health Yearbook Editorial Board.Chinese Health Yearbook.Beijing:People's Medical Publishing House,1995,413.
2 Zeamari S,Floot B,Van der Vange N,et al,Pharmacokinetics and pharmacodynamics of cisplatin after intraoperative hyperthermic intraperitoneal chemoperfusion(HIPEC).Anticancer Res,2003,23(2B):1643-1648.
3 Witkamp A J,de Bree E,Kaag MM,et al,Extensive cytoreductive surgery followed by intra-operative hyperthermic intraperitoneal chemotherapy with mitomycin-C in patients with peritoneal carcinomatosis of colorectal origin.Ur J Cancer,2001,37(8):979-841.
4 McQuellon RP,Loggie BW,Fleming RA,et al,Quality of life after intraperitoneal hyperthermic chemotherapy(IPHC)for peritoneal carcinomatosis.Eur J Surg Oncol,2001,27(1):65-73.
5 Miller AB,Hoogstratraten B,Staquet M,et al.Reporting results of cancer treatment.Cancer,1981,47,207.
6 Department of Medical Administration,Ministry of Health of P.R.China.Criteria of diagnosis and treatment of common malignant tumors in China,volume 9.Beijing:Beijing medical university and China Xiehe medical university joint publishing house,1991,10-15.
7 Zeamari S,Floot B,van der Vange N,et al,Pharmacokinetics and pharmacodynamics of cisplatin after intraoperative hyperthermic intraperitoneal chemoperfusion(HIPEC).Anticancer Res,2003,23(2B):1643-8.
8 Ruth S,Mathot RA,Sparidans RW,et al.Population pharmacokinetics and pharmacodynamics of mitomycin during intraoperative hyperthermic intraperitoneal chemotherapy.Clin Pharmacokinet,2004,43(2):131-31.
9 Panteix G,Beaujard A,Garbit F,et al.Population pharmacokinetics of cisplatin in patients with advanced ovarian cancer during intraperitoneal hyperthermia chemotherapy.Anti cancer Res,2002,22(2B):1329-361.
 
(Received Date:February 21,2005)
 
Author:Beijing Railway General Hospital 100038
 
Clinical Medicine,September,2005,25(9):34-36
 
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