Selective route of doxorubicin administration improves outcome in experimental malignant epidural cord compression.

Epidural spinal cord compression was produced in adult Fischer rats by injection of 10(6) viable cells of malignant fibrous histiocytoma anterior to the T-13 vertebral body. Using a tracer dye, it was demonstrated that a portion of the inoculum was always present in the anterior epidural space at the time of inoculation. Paraplegia and incontinence occurred consistently on Days 14 to 27 (median, 23 +/- 3.0). By sequential computed tomographic scans, the growth of the paravertebral tumor was documented and its volume was calculated. A single dose of cisplatin (i.p., 6 mg/kg) or doxorubicin (DXR, i.v. jugular, 6 mg/kg) was administered on Day 1. On Day 18, tumor volume was significantly reduced by DXR (P less than 0.001) and cisplatin (P less than 0.01), but paraplegia continued to occur as in the untreated rats. Comparison of treatment outcome with DXR administered via the jugular vs. the tail vein revealed that both were equally effective in retarding the growth of the paravertebral tumor, and both caused a similar transient leukopenia. However, only the tail DXR brought about a significant delay in the onset of paraplegia (P less than 0.004) and significantly increased the survival (P less than 0.001). It is suggested that the lack of efficacy of systemic chemotherapy for tumors located in the epidural space is probably related to inadequate drug exposure. The improved outcome with tail DXR infusion may be explained by the regional spinal venous perfusion, which allows an increase in the local drug concentration during its first passage through the epidural venous plexus.