STABILITY STUDIES ON CHEMOEMBOLIZATION MIXTURES - DIALYSIS STUDIES OFDOXORUBICIN AND LIPIODOL WITH AVITENE, GELFOAM, AND ANGIOSTAT

RATIONALE AND OBJECTIVES. Chemoembolization, using a combination of em bolic and chemotherapeutic agents, appears to be an effective treatmen t for hepatocellular carcinoma. Although the postulated mechanism of e ffectiveness hinges on a prolonged drug delivery, increasing evidence suggests that embolization mixtures are not stable. The objective of t his study was to investigate examples of these mixtures. METHODS. Dial ysis techniques have been used to examine the pharmacokinetic properti es of chemoembolization mixtures that contain doxorubicin, Lipiodol (G uerbet Products, Montreal, Quebec), and the embolizing agents Avitene (Alcon Laboratories Inc., Fort Worth, Texas), Gelfoam (Upjohn, Kalamaz oo, MI), and Angiostat (Regional Therapeutic Inc., Pacific Palisades, CA). RESULTS. Lipiodol, Gelfoam, and Avitene, when combined with doxor ubicin, had only a small effect on the diffusion of the drug when comp ared with the diffusion curve of doxorubicin alone. Gelfoam or Avitene produced a thrombus-like consistency when added to a doxorubicin/Lipi odol combination, and an additional decrease in the doxorubicin appear ance rate was observed. However, after 6 hours, doxorubicin levels for these mixtures reached control values observed in 3 hours. Angiostat without Lipiodol produced a profound concentration-dependent decrease in the diffusion of doxorubicin. After 9 hours, only 23% of the doxoru bicin had been released. CONCLUSION. The strong complexing ability of the embolic agent Angiostat may enable it to be a carrier for doxorubi cin and surpass other mixtures currently employed for transcatheter ch emoembolization.