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

Carlos A. Bagley, Markus J. Bookland, Jonathan A. Pindrik, Tolga Ozmen, Ziya L. Gokaslan, Timothy F Witham

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)194-198
Number of pages5
JournalJournal of Neurosurgery: Spine
Volume7
Issue number2
DOIs
StatePublished - Aug 2007

Fingerprint

Paresis
Spine
Neoplasms
Polymers
Inbred F344 Rats
Paclitaxel
Drug-Related Side Effects and Adverse Reactions
Paralysis
Spinal Cord
Adenocarcinoma
Breast
Theoretical Models
Extremities
Anesthesia
Animal Models
Neoplasm Metastasis
Drug Therapy
Control Groups
Injections
Therapeutics

Keywords

  • Local chemotherapy
  • Metastatic spinal tumor
  • Rat

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery
  • Neurology

Cite this

Local delivery of OncoGel delays paresis in rat metastatic spinal tumor model. / Bagley, Carlos A.; Bookland, Markus J.; Pindrik, Jonathan A.; Ozmen, Tolga; Gokaslan, Ziya L.; Witham, Timothy F.

In: Journal of Neurosurgery: Spine, Vol. 7, No. 2, 08.2007, p. 194-198.

Research output: Contribution to journalArticle

Bagley, Carlos A. ; Bookland, Markus J. ; Pindrik, Jonathan A. ; Ozmen, Tolga ; Gokaslan, Ziya L. ; Witham, Timothy F. / Local delivery of OncoGel delays paresis in rat metastatic spinal tumor model. In: Journal of Neurosurgery: Spine. 2007 ; Vol. 7, No. 2. pp. 194-198.
@article{f761af04e3cc4582826c7b15e6192107,
title = "Local delivery of OncoGel delays paresis in rat metastatic spinal tumor model",
abstract = "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.",
keywords = "Local chemotherapy, Metastatic spinal tumor, Rat",
author = "Bagley, {Carlos A.} and Bookland, {Markus J.} and Pindrik, {Jonathan A.} and Tolga Ozmen and Gokaslan, {Ziya L.} and Witham, {Timothy F}",
year = "2007",
month = "8",
doi = "10.3171/SPI-07/08/194",
language = "English (US)",
volume = "7",
pages = "194--198",
journal = "Journal of Neurosurgery: Spine",
issn = "1547-5654",
publisher = "American Association of Neurological Surgeons",
number = "2",

}

TY - JOUR

T1 - Local delivery of OncoGel delays paresis in rat metastatic spinal tumor model

AU - Bagley, Carlos A.

AU - Bookland, Markus J.

AU - Pindrik, Jonathan A.

AU - Ozmen, Tolga

AU - Gokaslan, Ziya L.

AU - Witham, Timothy F

PY - 2007/8

Y1 - 2007/8

N2 - 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.

AB - 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.

KW - Local chemotherapy

KW - Metastatic spinal tumor

KW - Rat

UR - http://www.scopus.com/inward/record.url?scp=34547686115&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547686115&partnerID=8YFLogxK

U2 - 10.3171/SPI-07/08/194

DO - 10.3171/SPI-07/08/194

M3 - Article

VL - 7

SP - 194

EP - 198

JO - Journal of Neurosurgery: Spine

JF - Journal of Neurosurgery: Spine

SN - 1547-5654

IS - 2

ER -