Abstract
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).
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1045-1049 |
| Number of pages | 5 |
| Journal | International Journal of Radiation Oncology Biology Physics |
| Volume | 51 |
| Issue number | 4 |
| DOIs | |
| State | Published - Nov 15 2001 |
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Keywords
- Blood-brain barrier
- Monoclonal antibody
- Radiotherapy
- Tumor model
ASJC Scopus subject areas
- Oncology
- Radiology Nuclear Medicine and imaging
- Radiation
Cite this
Efficacy after sequencing of brain radiotherapy and enhanced antibody targeted chemotherapy delivery in a rodent human lung cancer brain xenograft model. / Remsen, Laura G.; Marquez, Carol; Garcia, Raymond; Thrun, Lori A.; Neuwelt, Edward.
In: International Journal of Radiation Oncology Biology Physics, Vol. 51, No. 4, 15.11.2001, p. 1045-1049.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Efficacy after sequencing of brain radiotherapy and enhanced antibody targeted chemotherapy delivery in a rodent human lung cancer brain xenograft model
AU - Remsen, Laura G.
AU - Marquez, Carol
AU - Garcia, Raymond
AU - Thrun, Lori A.
AU - Neuwelt, Edward
PY - 2001/11/15
Y1 - 2001/11/15
N2 - 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).
AB - 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).
KW - Blood-brain barrier
KW - Monoclonal antibody
KW - Radiotherapy
KW - Tumor model
UR - http://www.scopus.com/inward/record.url?scp=0035889378&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035889378&partnerID=8YFLogxK
U2 - 10.1016/S0360-3016(01)01743-6
DO - 10.1016/S0360-3016(01)01743-6
M3 - Article
VL - 51
SP - 1045
EP - 1049
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
SN - 0360-3016
IS - 4
ER -