Toxicity and efficacy study of locally-delivered chemotherapy in a novel rat model of intramedullary spinal cord tumors

Gustavo Pradilla MD, Gaurav Mavinkurve BS, Federico G. Legnani MD, Betty M. Tyle MD, Neha Gosalia BA, Jonathan Pindrik BS, Alia Hdeib BA, Carlos A. Bagley MD, Henry Brem, MD, George Jallo MD
Department of Neurological Surgery, Johns Hopkins University, Baltimore, USA
E-mail: gjallo1@jhmi.edu

Introduction: Intramedullary spinal cord tumors (IMSCTs) are associated with significant morbidity/mortality and current treatment strategies for IMSCTs remain limited. Systemic chemotherapy has been unsuccessful for these tumors. Recent advances in local-drug-delivery systems make them ideal for IMSCTs. We report the toxicity of novel injectable chemotherapy-delivery systems Oncogel®(Taxol gel), SABER® (Carboplatin gel), and Paclimer® (Taxol-microspheres) in ratâ€TMs spinal cord, and the efficacy of Oncogel-1.5% in an IMSCT model using 9L-gliosarcoma in rats.

Methods: Toxicity: Fischer-344 rats (n=21) were randomized into 7 groups (3 rats/group) to receive an intramedullary injection (IMI) of either ReGel(empty gel), Oncogel-1.5%, Oncogel-6%, Saber-15%, Paclimer-2mg/kg, Paclimer-20mg/kg, or DMEM(Dulbeccoâ€TMs-modified-eagle-medium). Daily evaluation of hind limb motor function (using the BBB-Basso-Beattie-Bresnahan-scale) and weight gain were analyzed. Efficacy: Fischer-344 rats (n=12) were randomized into 3 groups (4/group), group 1 received an IMI of 9L cells, groups 2 and 3 received an IMI of 9L, plus Oncogel-1.5% or ReGel, respectively; animals were assessed daily using the BBB scale.

Results: Toxicity: Animals treated with Oncogel-6% showed acute toxicity (1 animal died on day 4, 3 animals were euthanized due to complete paraplegia on day 5), animals in other groups showed weight gain and maximal BBB scores throughout the experiment. Efficacy: Group 1 (controls) had median onset of paralysis (MOP) of 10 days, Group 2 (Oncogel-1.5%) had no significant motor deficit by day 20, Group 3 (ReGel) had MOP of 14±1.4 days.

Conclusions: Locally-delivered chemotherapy, with the exception of Oncogel-6%, was well tolerated by the animals. Oncogel-1.5% significantly prolonged onset of paralysis. Further studies are needed to determine the efficacy of SABER and Paclimer for IMSCTs.

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