Effects of bevacizumab and hyperthermia in a rodent model of hyperthermic intraperitoneal chemotherapy (HIPEC)

Abstract

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) is more and more used in the treatment of patients with peritoneal carcinomatosis (PC) of different primary tumours. However, survival of patients with PC is still poor. The aim of this study was to evaluate the effects of preoperatively administered bevacizumab and temperature of the perfusion in an experimental model of HIPEC.Materials and methods: A model for peritoneal carcinomatosis of colorectal origin was created by implantation of tumour fragments (HT29) in the abdomen of athymic nude rats. All animals were treated with oxaliplatin-based HIPEC. Animals were randomised into different treatment groups: hyperthermic treatment was compared to normothermic treatment and in both groups there were animals with and without preoperative administration of bevacizumab. Interstitial fluid pressure (IFP), bio-availability (concentrations of the drug in blood and tumour) and tumour growth delay (TGD) were evaluated.Results: In this study, preoperative bevacizumab lowered IFP but there was no effect on the bio-availability. The effect on the size of the tumour was ambivalent with no statistically significant effect on TGD. The area under the curve (AUC) of platinum was higher in animals treated with hyperthermic perfusion as compared to normothermic perfusion. In the TGD-study a post-operative mortality of 100% was observed in the hyperthermic group, compared to 1 out of 16 rats in the normothermic group.Conclusions: The results of this study suggest that bevacizumab is not promising for clinical implementation in the setting of HIPEC: the effects on tumour size were ambivalent and there was no statistically significant benefit in TGD. The effects of hyperthermic perfusion in this study were negative: a higher blood concentration of oxaliplatin as compared to normothermic perfusion, without a higher intra-tumoural concentration. There was a higher mortality rate after hyperthermic perfusion as compared to normothermic perfusion (p < 0.001).