ADJUVANT TREATMENT WITH LOCALLY DELIVERED ONCOGEL DELAYS THE ONSET OF PARESIS AFTER SURGICAL RESECTION OF EXPERIMENTAL SPINAL COLUMN METASTASIS

Abstract

The optimal management of spinal column metastatic disease is controversial. Local chemotherapy delivery systems allow targeted high-dose adjuvant therapy. We evaluated whether injection of OncoGel paclitaxel-releasing biodegradable polymer (Protherics, Inc., West Valley City, UT) into the tumor resection cavity at the time of surgery would improve the efficacy of surgical resection with or without external beam radiotherapy (XRT) in a rat model of spinal column metastases. Fischer-344 rats (Charles River Laboratories, Wilmington, MA) underwent a transabdominal approach for implantation of a CRL-1666 breast adenocarcinoma cell line within the L6 vertebral body. In experiment 1, 7 days after tumor implantation, animals underwent 1 of 2 treatments or no treatment (n = 8 per group): control (no treatment); surgery alone (L6 corpectomy); or surgery + OncoGel (L6 corpectomy with OncoGel implantation into the resection cavity). In experiment 2, 7 days after tumor implantation, animals underwent 1 of 2 treatments or no treatment (n = 8 per group): control (no treatment); surgery + XRT (L6 corpectomy followed by XRT [total 20 Gy]); or surgery + XRT + OncoGel (L6 corpectomy with OncoGel implantation followed by XRT). In experiment 3, 7 days after tumor implantation, animals underwent 1 of 2 treatments or no treatment (n = 8 per group): control (no treatment); XRT alone (total 20 Gy); or XRT + OncoGel. Daily hindlimb function was assessed using the Basso, Beattie, and Bresnahan (BBB) scale (range, 1-21). In experiment 1, both treatment groups had delayed onset of paresis compared with control. Compared with surgery alone, surgery + OncoGel resulted in superior median BBB scores on posttreatment days 9 (21 versus 19, P < 0.001) through 14 (11 versus 8, P < 0.005). In experiment 2, both treatment groups had delayed onset of paresis compared with control. Compared with surgery + XRT, surgery + XRT + OncoGel resulted in superior median BBB scores on posttreatment days 13 (21 versus 19, P < 0.001) through 17 (12 versus 8, P < 0.005). Median time to loss of ambulation (BBB scale score </=7) was maximized by the addition of OncoGel to surgery plus XRT: control (8.5 days), surgery alone (13.5 days), surgery + OncoGel (16 days), surgery + XRT (17 days), and surgery + XRT + OncoGel (19 days). In experiment 3, both treatment groups had delayed onset of paresis compared with control. Compared with XRT alone, XRT + OncoGel resulted in superior median BBB scores on posttreatment days 6 (21 versus 19, P < 0.001) through 11 (13 versus 8, P < 0.005). However, compared with surgery + XRT + OncoGel, XRT + OncoGel resulted in worse median BBB scores on posttreatment days 8 (20 versus 21, P < 0.01) through 13 (7 versus 19, P < 0.005). In a rat model of spinal metastatic disease, local delivery of OncoGel increased the efficacy of surgery and radiotherapy and delayed the onset of neurological decline. These results suggest that OncoGel may be an effective adjuvant therapy in the operative management of metastatic spinal column tumors and that combining local chemotherapy with surgery and adjuvant radiotherapy may improve outcomes of this disease.