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A. D. Kulkarni, B. E. Radke, E. M. Gates, S. R. Darjatmoko, D. M. Albert; Use of Combination Therapy With Calcitriol and Cisplatin in the Treatment of Y-79 Human Retinoblastoma Tumor Model. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5245.
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To compare efficacy and toxicity of combination therapy with calcitriol and cisplatin versus monotherapy with cisplatin in athymic mice with subcutaneous Y-79 human retinoblastoma tumors.
60 athymic mice were subcutaneously injected with 5 x 106 human Y79 retinoblastoma cells. Animals were randomized into four groups: group 1 - 50 µg of cisplatin in 0.25 ml of saline and 0.1 ml of vehicle; group 2 - 0.05µg of calcitriol in 0.1 ml of vehicle and 0.25 ml saline; group 3 - 0.05µg of calcitriol in 0.1 ml of vehicle and 50 µg of cisplatin in 0.25 ml of saline and group 4 -0.1 ml vehicle and 0.25 ml saline (control). All the dosing solutions were injected intraperitoneally. The calcitriol, vehicle and saline were administered 5 times a week for 5 weeks whereas the cisplatin was injected once a week for 5 weeks. Tumor size and body weights were recorded 2 times a week. The animals were euthanized at the end of the study and tumor volume, and serum calcium levels were measured. A histopathologic examination of tumor and kidney was performed.
The mean end tumor volume was as follows: For cisplatin treated animals (group 1) 1117.40 mm3 (p=0.0120); for calcitriol treated animals (group 2) 735.63 mm3 (p=0.0001); for combination therapy with calcitriol and cisplatin (group3) 651.27 mm3 (p=0.0001). In all these groups the mean end tumor volume was significantly lower than 1717.67 mm3 in the controls (group 4). Further subset analysis revealed that the mean end tumor volume was significantly less after combination therapy with calcitriol and cisplatin (651.27 mm3) as compared to cisplatin alone (1117.40 mm3, p=0.0041). The initial and the end body weight were not statistically different in any of the groups. There was no mortality due to the toxic effects of the treatment regimen in the various groups.
The addition of calcitriol increased the effectiveness of cisplatin without additional toxicity in the doses studied.
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