Abstract
Abstract Hyperthermic intraperitoneal chemotherapy (HIPEC) combines circulated chemotherapy with enhanced temperature in the abdominal cavity of peritoneal carcinosis (PC) patients. Unfortunately, a standardized HIPEC protocol is missing hindering systematic comparisons with regard to minimal effective temperatures. The purpose of the present study was to systematically analyse the temperature needed for potentiation of chemotherapy effects in vitro. We then asked if this temperature could be sustained in patients during HIPEC and evaluated possible effects on survival. We therefore established a cell line-based model to mimic HIPEC conditions used in clinic. We evaluated intracellular drug concentrations and long-term survival using different temperatures ranging from 38 to 42°C combined with Cisplatin and Doxorubicin. In parallel we evaluated the temperature reached in the clinical setting by measuring inflow and outflow, as well as in the peritoneal cavity in 36 PC patients. Finally we determined the influence of different temperatures on survival. In vitro, we found temperature-dependent effects on intracellular drug concentration and long term survival only at temperatures above 40°C. In patients, during HIPEC, constant temperatures were reached after 10 minutes in the peritoneal cavity. A temperature above 40°C for at least 45 minutes was achieved in 67% or 44% of patients with HIPEC in open or closed abdomen, respectively. Importantly, we observed a significantly enhanced overall survival as well as a trend towards longer recurrent free survival in those patients with HIPEC temperatures above 40°C. In conclusion, hyperthermia significantly potentiated the chemotherapy effects only at temperatures above 40°C in vitro. Importantly, this temperature threshold was also critical for overall and recurrent-free survival of PC patients. Citation Format: Lea Schaaf, Marina Münch, Wolfgang Steurer, Walter E. Aulitzky, Thomas E. Mürdter, Heiko van der kuip, Christoph Ulmer. HIPEC for treatment of peritoneal carcinomatosis: 40°C is the critical threshold temperature for potentiating chemotherapy efficacy in vitro and in vivo. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2574. doi:10.1158/1538-7445.AM2015-2574
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call