Local delivery of OncoGel delays paresis in rat metastatic spinal tumor model

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Object.

Spinal column metastatic disease clinically affects thousands of cancer patients every year. Local chemotherapy represents a new option in the treatment of metastatic disease of the spine. Despite the clinical impact of metastatic spine disease, the literature currently lacks an accurate animal model for the effective dosing of local chemotherapeutic agents within the vertebral column.

Methods.

Female Fischer 344 rats, weighing 150 to 200 g each, were used in this study. After induction of anesthesia, a transabdominal approach to the ventral vertebral body of L-6 was performed. A small hole was drilled and 5 μL of ReGel (blank polymer), OncoGel (paclitaxel and ReGel) 1.5%, OncoGel 3.0%, or OncoGel 6.0% were immediately injected to determine drug toxicity. Based on these results, efficacy studies were performed by intratumoral injection of 5 μL of ReGel, OncoGel 3.0%, and OncoGel 6.0% on Day 6 in a CRL-1666 breast adenocarcinoma metastatic spine tumor model. Hind limb function was tested pre- and postoperatively using the Basso-Beattie-Bresnahan rating scale. Histological analysis of the spinal cord and vertebral column was performed when the animal died or was killed.

Results.

There were no signs of toxicity observed in association with any of the agents under study. No increased benefit was seen in the blank polymer group compared with the control group (tumor only). OncoGel 3.0% and OncoGel 6.0% were effective in delaying the onset of paralysis in the respective study groups.

Conclusions.

These findings demonstrate the potential benefit of OncoGel in cases of subtotal resections of metastatic spinal column tumors. OncoGel 6.0% is the most efficacious drug concentration and offers the best therapeutic option in this experimental model. These results provide promise for the development of local chemotherapeutic means to treat spinal metastases.

Abbreviations used in this paper:BBB = Basso-Beattie-Bresnahan; VB = vertebral body.

Article Information

Address reprint requests to: Timothy F. Witham, M.D., Department of Neurosurgery, Meyer Building 7–109, Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, Maryland 21287–7713. email: twitham2@jhmi.edu.

© AANS, except where prohibited by US copyright law.

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Figures

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    Graph displaying the average BBB locomotor rating scale scores of each group of rats throughout the investigation. The dashed vertical line indicates post–tumor implantation Day 6, when animals received intratumoral ReGel (control) or OncoGel treatments. Bars indicate standard errors of the means (SEM).

  • View in gallery

    Graph displaying Kaplan–Meier survival curves for each group. The solid vertical line indicates post–tumor implantation Day 6, when animals received intratumoral ReGel (control) or OncoGel treatments.

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