INVIVO EFFECTS OF CAVITATION ALONE OR IN COMBINATION WITH CHEMOTHERAPY IN A PERITONEAL CARCINOMATOSIS IN THE RAT

Cavitation (volume oscillations and collapse of gas bubbles), as gener ated by a co-administration of shockwaves (SW) and microbubbles (SWB), induces cytotoxicity in vitro. Moreover, cavitation potentiates the e ffects of Fluorouracil (FUra) on colon cancer cells. We aimed at repro ducing such effects in vivo. A peritoneal carcinomatosis was induced i n BDIX rats by intraperitoneal (IP) injection of DHDK12PROb cells. Cav itation was produced by various SW regimens (250 to 750SW) combined wi th bubbles (air/gelatin emulsion) infused through an IP catheter. In t wo consecutive experiments, microtumours (day 3 after cell injection) were submitted to various combinations of cavitation and/or Fluorourac il (FUra) and Cisplatinum (CDDP) at either high or low doses. After 30 days, 100% of control animals were dead or presented carcinomatosis w ith ascites, vs 60% after FUra 5 mg kg dy, day 4 through 8, and 0% aft er 250 SWB, day 4 and 6 + FUra 5 mg kg dy, day 4 through 8 (P <0.00 1) ; similar differences were found with CDDP. Survival after low dose FU ra + SWB was comparable to high dose FUra (25 mg kg dy day 4 through 8 ) and was improved as compared to low-dose FUra alone. Only a high dos e FUra + SWB schedule induced 40% long term (> 150 days) disease-free survival, but also a higher undesirable toxicity (40% toxic deaths wit hin 1 month). It is concluded that cavitation is cytotoxic in vivo and that it potentiates the effects of FUra and CDDP in this animal model .