Adjuvant Treatment with Locally Delivered Oncogel Delays the Onset of Paresis after Surgical Resection or Radiotherapy of Experimental Spinal Column Metastasis

INTRODUCTION: 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) into the tumor resection cavity at the time of surgery would improve the efficacy of surgical resection with or without radiotherapy in a rat model of spinal column metastases. METHODS: Fisher 344 rats underwent a transabdominal approach for implantation of a CRL-1666 breast adenocarcinoma cell line within the L6-vertebral body. Experiment 1: 7 days after tumor implantation, animals underwent (n = 8/group): 1) control: no treatment; 2) surgery alone: L6 corpectomy, or 3) surgery + OncoGel: L6 corpectomy with Oncogel implantation into the resection cavity. Experiment 2: 7 days after tumor implantation, animals underwent (n = 8/group) 1) control: no treatment, 2) surgery + XRT: L6 corpectomy followed by XRT (total 20 Gy), or 3) surgery + XRT + OncoGel, L6 corpectomy with Oncogel implantation followed by XRT. Experiment 3: 7 days after tumor implantation, animals underwent (n = 8/group): 1) control: no treatment; 2) XRT alone: XRT(total 20 Gy); or 3) XRT+ Oncogel: intratumoral Oncogel injection followed by XRT (total 20 Gy). Daily hind-limb function was assessed using the Basso-Beattie-Bresnahan (BBB) scale (range, 1–21). RESULTS: Experiment 1: both treatment groups delayed onset of paresis compared with the control. Compared with surgery alone, surgery + Oncogel resulted in superior median BBB scores after treatment Days 9 (21 versus 19, P < 0.001) through 14 (11 versus 8, P < 0.005). Experiment 2: both treatment groups delayed onset of paresis compared with the control. Compared with surgery + XRT, Surgery + XRT + OncoGel resulted in superior median BBB scores after treatment Days 13 (21 versus 19, P < 0.001) through 17 (12 versus 8, P < 0.005). Median time to paralysis was maximized by the addition of Oncogel to surgery plus radiotherapy: (control [8.5 d], surgery alone [13.5 d], surgery + Oncogel [16 d], surgery + XRT [17 d], surgery + XRT + OncoGel group [19 d]). Experiment 3: compared with XRT alone, XRT + Oncogel resulted in superior median BBB scores after treatment Days 7 (21 versus 18, P < 0.001) through 11 (13 versus 8, P < 0.005). Median time to paralysis was improved with XRT + Oncogel (13 d) versus XRT alone (10 d, P < 0.001). CONCLUSION: In a rat model of spinal metastatic disease, local delivery of Oncogel increased the efficacy of surgery and radiotherapy in prevention of neurological decline. These results suggest that Oncogel may be an effective adjuvant therapy in both the operative and nonoperative management of metastatic spinal tumors.