Optimization of combination therapy of arsenic trioxide and fractionated radiotherapy for malignant glioma.
OBJECTIVE
The primary objective was to optimize the combined treatment regimen using arsenic trioxide (ATO) and fractionated radiotherapy for the treatment of malignant glioma.


METHODS
Nude mice with human glioma xenograft tumors were treated with fractionated local tumor radiation of 250 cGy/fraction/day and 5 mg/kg ATO for 5-10 days.


RESULTS
Time course experiments demonstrated that maximal tumor growth delay occurred when ATO was administered between 0 and 4 h after radiation. The combination treatment of ATO and radiation synergistically inhibited tumor growth and produced a tumor growth delay time of 13.2 days, compared with 1.4 days and 6.5 days for ATO and radiation alone (p < 0.01), respectively. The use of concurrent therapy of radiation and ATO initially, followed by ATO as maintenance therapy, was superior to the use of preloading with ATO before combined therapy and produced a tumor growth delay time of 22.7 days as compared with 11.7 days for the ATO preloading regimen (p < 0.01). The maintenance dose of ATO after concurrent therapy was effective and important for continued inhibition of tumor growth.


CONCLUSIONS
The combined use of fractionated radiation and ATO is effective for the treatment of glioma xenograft tumors. ATO was most effective when administered 0-4 h after radiation without pretreatment with ATO. These results have important implications for the optimization of treatment regimen using ATO and fractionated radiotherapy for the treatment of brain tumors.
Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA 94305-1245, USA.
Shoucheng
S
Ning
Susan J
SJ
Knox
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy / Q000379:methods; D019583:Dose Fractionation, Radiation; D005910:Glioma / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010087:Oxides / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D000077237:Arsenic Trioxide