Current standard in treatment of peritoneal carcinomotisis. Data behind the HIPEC trials

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1 Current standard in treatment of peritoneal carcinomotisis Data behind the HIPEC trials

2 Overview Peritoneal carcinomatosis STANDARD treatment HIPEC Results of treatment Counter side of treatment

3 Peritoneal carcinomatosis a local regional disease

4 Stage IV colorectal cancer Metastasized colorectal cancer Liver metastasis Lung metastasis Intra abdominal Intra luminal 9% 9% 34% 34% 9% 9% 48% 48% intra abdominal liver lung intraluninal intra abdominal liver lung intraluninal

5 Treatment stage IV colorectal carcinoma Systemic chemotherapy median survival up to 20 months

6 Bevacizumab plus irinotecan fluoroururacil and leucovorin for metastatic colorectal cancer IFL + placebo IFL + bevacizumab Gender Male Female Mean age ECOG perform <1 <1 Type of cancer Colon Rectum N of metastatic sites (%) 1 > Prior cancer therapy (%) Adjuvant chemoth Radiotherapy NEJM 2004; 350:

7 Bevacizumab plus irinotecan fluoroururacil and leucovorin for metastatic colorectal cancer (n=923) End point IFL + placebo IFL + bevacizumab HR p Median survival < year survival PF survival < Response rate Complete Partial Duration of responce NEJM 2004; 350:

8 Inclusion in stage IV chemotherapy Measurable disease (RECIST criteria) 23% 9% Intra abdominal Liver Lung 68% Intra abdominal Liver Lung

9 The difference in disease Measurable disease Peritoneal carcinatosis

10 Data on systemic treatment of PC Median 6 months overall survival Sadeghi e.a. Cancer 2000; 88: Jayne e.a. Br J Surg 2002; 89: Median 12 months overall when treated Bloemendaal EJSO 2005; 31:

11 Phase II data, collected n= 506 Glehen, O. et al. J Clin Oncol 2004; 22:

12 Questions on these data Different methods MMC or oxaliplatine Open or closed EPIC or no EPIC Different selection criteria

13 Original randomized trial Random ized Random ized 105 patients 105 patients Standard treatm ent Standard treatm ent 51 patients 51 patients Experim ental therapy Experim ental therapy 54 patients 54 patients probability probability months Started chem otherapy Started chem otherapy 44 patients 44 patients standard treatment standard HIPEC treatment HIPEC P = months Treated by HIPEC Treated by HIPEC 49 patients 49 patients Started adjuvant therapy Started adjuvant therapy 35 patients 35 patients survival 18 in months survival in months

14 Protocol for the updated trial On original patients and randomization Cross-over patients were censored at cross over 2 Patients were crossed over Follow-up complete in all patients Median follow-up 94 months

15 Survival updated data Probability Probability Kaplan-Meier Kaplan-Meier survival survival estimates, estimates, by by arm arm P = months 12.6 months arm = Standard arm = Standard arm = HIPEC arm = HIPEC Time 36 in 42 months Time in months

16 Patients treated long term Probability Probability Kaplan-Meier Kaplan-Meier survival survival estimates, estimates, by by recidual recidual R-1 R-1 R-2a R-2a R-2b R-2b Time 36 in 42 months Time in months

17 Learning effect Med surv R1 no tox Smeek et al BJS 2007

18 Mortality Mortality

19 Dutch HIPEC organization Amsterdam Groningen Nieuwegein Eindhoven

20 Dutch Organization The Netherlands Cancer institute Active from 1995, 436 patients treated Antonius Hospital Active from 2005, 80 patients treated UMCG Active from 2006, 26 patients treated Catharina Hospital Active from 2007, 20 patients treated

21 Results in the Netherlands Probibility Survival after HIPEC in the Netherlands ( n = 562) Months

22 Summary Peritoneal Carcinomatosis can be successful treated with Cytoreduction followed by HIPEC and adjuvant chemotherapy Peritoneal Carcinomatosis is a special sub-group of stage IV colorectal cancer

23 Stage IV colorectal cancer Resection data Medial survival 32 months Local Liver and lung Intra abdominal Chemotherapy data Medial survival 21 months HIPEC data Medial survival 22 months

24 Thanks for the attention

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