Extravascular use of drug-eluting beads: a promising approach in compartment-based tumor therapy

Abstract

Intraperitoneal carcinomatosis (PC) may occur with several tumor entities. The prognosis of patients suffering from PC is usually poor. Present treatment depends on the cancer entity and includes systemic chemotherapy, radiation therapy, hormonal therapy and surgical resection. Only few patients may also benefit from hyperthermic intraperitoneal chemotherapy with a complete tumor remission. These therapies are often accompanied by severe systemic side-effects. One approach to reduce side effects is to target chemotherapeutic agents to the tumor with carrier devices. Promising experimental results have been achieved using drug-eluting beads (DEBs). A series of in vitro and in vitro experiments has been conducted to determine the suitability of their extravascular use. These encapsulation devices were able to harbor CYP2B1 producing cells and to shield them from the hosts immune system when injected intratumorally. In this way ifosfamide--which is transformed into its active metabolites by CYP2B1--could be successfully targeted into pancreatic tumor growths. Furthermore DEBs can be used to target chemotherapeutics into the abdominal cavity for treatment of PC. If CYP2B1 producing cells are proven to be save for usage in man and if local toxic effects of chemotherapeutics can be controlled, DEBs will become promising tools in compartment-based anticancer treatment.

Keywords: CYP2B1; Carcinomatosis; Compartment based therapy; Drug-eluting beads; Glioblastoma; Hyperthermic intraperitoneal chemotherapy; Ifosfamide; Intraperitoneal; Pancreatic cancer.

Figures

Figure 1

Peritoneal metastasis. A: Beads accumulate in the mesentery of the small bowel (arrors). Animals show a complete tumor remission; B: Control animal with disseminated peritoneal carcinomatosis induced by EGFP-C-26 cells.

Figure 2

Doxorubicin-eluting beads. A: HE-stained, magnification × 50: A layer of fibrin (between arrows) immobilizing the doxorubicin-loaded DC beads (DOXDEB™) on the livers surface; B: HE-stained, magnification × 100: DOXDEB™ in layer of fibrin and surrounded by lymphocytes immobilizing it on mesenteric connective tissue.

Figure 3

Chemical peritonitis. Autopsy of an animal 28 d after installation of ip doxorubicin-loaded drug-eluting beads: Situs with greater omentum and intestinal loops with fibrinous adhesions, amber-colored ascitic fluid.