Local delivery of oncogel delays paresis in rat metastatic spinal tumor model.
OBJECTIVE
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 microL 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 microL 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.
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21827-7713, USA.
Carlos A
CA
Bagley
Markus J
MJ
Bookland
Jonathan A
JA
Pindrik
Tolga
T
Ozmen
Ziya L
ZL
Gokaslan
Timothy F
TF
Witham
D000230:Adenocarcinoma / Q000473:pathology / Q000556:secondary; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005260:Female; D015552:Injections, Intralesional; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D010291:Paresis / Q000209:etiology / Q000517:prevention & control*; D011108:Polymers; D051381:Rats; D011916:Rats, Inbred F344; D013125:Spinal Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000556:secondary*; D016019:Survival Analysis
D000972:Antineoplastic Agents, Phytogenic; D011108:Polymers; D017239:Paclitaxel