Comparison of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a murin model of peritoneal carcinomatosis

Abstract

BackgroundThe best method to deliver intraperitoneal chemotherapy (IPC) for peritoneal carcinomatosis from ovarian cancer is not well defined. The aim of this study was to assess the ability of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a rat model of peritoneal carcinomatosis.MethodsFour groups of 5 BDIX rats with ovarian peritoneal carcinomatosis underwent IPC with 30 mg/l of cisplatin according to the following conditions: normothermia at 37° for 1 or 2 hours, hyperthermia at 42°C for 1 hour or normothermia at 37°C for 2 hours with 2 mg/l adrenaline. Tissue platinum content was measured by atomic absorption spectroscopy. The effect of hyperthermia, adrenaline and the duration of exposure to the drug was measured in vivo (tissue concentration of platinum in tumor, abdominal and extra abdominal tissues) and in vitro (cytotoxicity on human ovarian cancer cells).ResultsIn vitro, hyperthermia and longer exposure enhanced the accumulation and the cytotoxic effect of cisplatin on cancer cells. In vivo, only the 2 hours treatment with adrenaline resulted in increased platinum concentrations. The rats treated with adrenaline showed significantly lower concentrations of cisplatin in extra peritoneal tissues than those treated with hyperthermia.ConclusionAdrenaline is more effective than hyperthermia in order to enhance the intratumoral concentration of cisplatin in rats with peritoneal carcinomatosis from ovarian origin. It may also decrease the systemic absorption of the drug.

The intratumoral administration of ferucarbotran conjugated with doxorubicin improved therapeutic effect by magnetic hyperthermia combined with pharmacotherapy in a hepatocellular carcinoma model

“…Tumors are usually heated to the temperature range of 41-47°C, and cancer tissues exhibit higher heat sensitivity than normal tissues [20]. It also has been believed that the drug delivery to target could be increased by hyperthermia through its effects on convection and diffusion in tissues, increasing cell uptake of the drug, tumor blood flow and vascular permeability [21]. In our study, Resovist or the Resovist/doxorubicin complex also induced temperature increases to approximately 41°C ( Figure 5A).…”

High Pressure Enhances the Effect of Hyperthermia in Intraperitoneal Chemotherapy With Oxaliplatin

“…9,[14][15][16][17][18][19][20] However, comparisons between these methods are lacking, as are pharmacokinetic and pharmacodynamic data to prove their effect. Furthermore, the results obtained with one drug are not necessarily the same as those with another.…”

“…Hyperthermia is widely used to this end, even though it is not effective with all chemotherapy drugs. [7][8][9] Five years ago, our group showed that high pressure closed intraperitoneal chemotherapy with cisplatin increased cisplatin penetration into the peritoneum, and increased survival in rats with peritoneal carcinomatosis of colorectal origin. 10 As open techniques of HIPEC might achieve better tissue concentrations than closed techniques according to a previous experimental work, 11 we hypothesized that high pressure could be achieved during open HIPEC.…”

Rhenium–platinum antitumor systems

“…A lot of studies have explored the potential of platinum-based combination therapy [19] that means to combine one, two or more known non-platinum anticancer drugs with a platinum compound, for example [20][21][22][23][24][25]. Such a combination leads to synergistic effects and/or to lowering toxicity of platinum-based drugs and is very promising in cancer chemotherapy.…”