Efficacy after sequencing of brain radiotherapy and enhanced antibody targeted chemotherapy delivery in a rodent human lung cancer brain xenograft model.
OBJECTIVE
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
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).
Remsen
L G
LG
Department of Neurology, Oregon Health Sciences University, Portland, OR, USA.
Marquez
C
C
Garcia
R
R
Thrun
L A
LA
Neuwelt
E A
EA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000556:secondary; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000532:radiotherapy* / Q000556:secondary; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000473:pathology*; D011897:Random Allocation; D051381:Rats; D011923:Rats, Nude; D016019:Survival Analysis; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C092612:BR96-doxorubicin immunoconjugate; D000922:Immunotoxins; D004317:Doxorubicin