Efficacy after sequencing of brain radiotherapy and enhanced antibody targeted chemotherapy delivery in a rodent human lung cancer brain xenograft model

Purpose: The objective of this study was to evaluate the efficacy of sequencing radiation therapy (RT) and antibody targeted chemotherapy (BR96-DOX) in nude rats bearing human lung cancer (B.5 LX-1) intracerebral (i.c.) xenografts. Methods and Materials: Our approach was to administer RT using 20 Gy single-fraction cranial irradiation either before, concurrent with, or after BR96-DOX treatment via osmotic blood-brain barrier disruption to enhance immunoconjugate delivery. All rats were inoculated with i.c. B.5 LX-1 tumors and were randomly assigned to treatment groups. Results: BR96-DOX alone on Day 6 or Day 12 significantly increased survival compared to negative control rats receiving no treatment (25.9 ± 2.1 and 23.3 ± 2.5 days vs. 14.8 ± 1.9 days, p < 0.05). Rats that received chemotherapy before radiation (34.0 ± 2.0 days) lived the longest compared to the other sequences (RT prior, 29.5 ± 1.9; RT concurrent, 27.1 ± 2.1). Histopathology of 39 rat brains did not reveal any neuropathology. Conclusions: Enhanced delivery of immunoconjugates is more effective in combination with RT for the treatment of experimental metastatic brain tumors. Moreover, BR96-DOX administration prior to RT significantly increased survival compared to those receiving RT and chemotherapy concurrently (p < 0.05).