Current standard in treatment of peritoneal carcinomotisis Data behind the HIPEC trials
Overview Peritoneal carcinomatosis STANDARD treatment HIPEC Results of treatment Counter side of treatment
Peritoneal carcinomatosis a local regional disease
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
Treatment stage IV colorectal carcinoma Systemic chemotherapy median survival up to 20 months
Bevacizumab plus irinotecan fluoroururacil and leucovorin for metastatic colorectal cancer IFL + placebo IFL + bevacizumab Gender Male Female 60 40 59 41 Mean age 59.2 59.5 0 55 58 ECOG perform. 1 44 41 2 <1 <1 Type of cancer Colon Rectum 81 19 77 23 N of metastatic sites (%) 1 >1 39 61 37 63 Prior cancer therapy (%) Adjuvant chemoth Radiotherapy 28 14 24 15 NEJM 2004; 350: 2335-2342
Bevacizumab plus irinotecan fluoroururacil and leucovorin for metastatic colorectal cancer (n=923) End point IFL + placebo IFL + bevacizumab HR p Median survival 15.6 20.3 0.66 < 0.001 1 year survival 63.4 74.3 PF survival 6.2 10.6 0.54 < 0.001 Response rate 34.8 44.8 0.004 Complete 2.2 3.7 Partial 32.6 41.0 Duration of responce 7.1 10.4 0.62 0.001 NEJM 2004; 350: 2335-2342
Inclusion in stage IV chemotherapy Measurable disease (RECIST criteria) 23% 9% Intra abdominal Liver Lung 68% Intra abdominal Liver Lung
The difference in disease Measurable disease Peritoneal carcinatosis
Data on systemic treatment of PC Median 6 months overall survival Sadeghi e.a. Cancer 2000; 88: 358 363 Jayne e.a. Br J Surg 2002; 89: 1545 1550 Median 12 months overall when treated Bloemendaal EJSO 2005; 31: 1145-1141
Phase II data, collected n= 506 Glehen, O. et al. J Clin Oncol 2004; 22: 3284-3292
Questions on these data Different methods MMC or oxaliplatine Open or closed EPIC or no EPIC Different selection criteria
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 1.00 1.00 0.80 0.80 0.60 0.60 0.40 0.40 0.20 0.20 12.6 months Started chem otherapy Started chem otherapy 44 patients 44 patients standard treatment standard HIPEC treatment HIPEC P =.032 22.3 months Treated by HIPEC Treated by HIPEC 49 patients 49 patients Started adjuvant therapy Started adjuvant therapy 35 patients 35 patients 0.00 0.00 0 6 12 18 24 30 36 0 6 12 survival 18 in months 24 30 36 survival in months
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
Survival updated data Probability Probability 1.0 1.0 0.9 0.9 0.8 0.8 0.7 0.7 0.6 0.6 0.5 0.5 0.4 0.4 0.3 0.3 0.2 0.2 0.1 0.1 0.0 0.0 Kaplan-Meier Kaplan-Meier survival survival estimates, estimates, by by arm arm P =.028 22.2 months 12.6 months arm = Standard arm = Standard arm = HIPEC arm = HIPEC 0 6 12 18 24 30 36 42 48 54 60 66 72 78 0 6 12 18 24 30 Time 36 in 42 months 48 54 60 66 72 78 Time in months
Patients treated long term Probability Probability 1.0 1.0 0.9 0.9 0.8 0.8 0.7 0.7 0.6 0.6 0.5 0.5 0.4 0.4 Kaplan-Meier Kaplan-Meier survival survival estimates, estimates, by by recidual recidual R-1 R-1 R-2a R-2a R-2b R-2b 0.3 0.3 0.2 0.2 0.1 0.1 0.0 0.0 0 6 12 18 24 30 36 42 48 54 60 66 72 78 0 6 12 18 24 30 Time 36 in 42 months 48 54 60 66 72 78 Time in months
Learning effect 80 70 71 73 60 50 40 30 20 27.6 19.7 20.8 25 40 32 36 95-98 98-01 01-05 10 0 Med surv R1 no tox Smeek et al BJS 2007
Mortality Mortality 10 9 8 7 6 5 4 3 2 1 0 95-98 98-01 01-05
Dutch HIPEC organization Amsterdam Groningen Nieuwegein Eindhoven
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
Results in the Netherlands Probibility 1.00 0.90 0.80 0.70 0.60 0.50 0.40 0.30 0.20 0.10 0.00 Survival after HIPEC in the Netherlands ( n = 562) 0 12 24 36 48 60 72 84 96 108 120 132 Months
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
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
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