Table 1.

Toxicity parameters for solid and “liquid” tumor models treated with metronomic CTX, Vbl, Nvb, or CDDP


Tumor model (description), drug, and drug dose, mg/kg

Total WBC count, per μL PB

Neutrophil counts, per 104 PB cells

Lymphocyte counts, per 104 PB cells

Bone marrow proliferation, cpm/105 cells

Body weight, g
MeWo (human melanoma), CTX      
    0   4.06 ± 2.38   7.41 ± 4.13   11.29 ± 11.34   9563 ± 3045   24.46 ± 1.20  
    10   2.62 ± 0.65   7.23 ± 3.79   13.01 ± 5.70   12460 ± 3079   26.67 ± 0.94  
    20   1.24 ± 0.63   6.69 ± 3.20   5.99 ± 2.00   10776 ± 1949   25.85 ± 1.91  
    40   1.02 ± 0.22   4.02 ± 1.78   6.93 ± 3.36   8844 ± 372   24.09 ± 2.56  
    50   0.76 ± 0.42   2.00 ± 1.38*  6.17 ± 4.52   6359 ± 1908   22.61 ± 1.03  
MDA-MB-231/MVB9 (human breast cancer, resistant to Vbl), Vbl      
    0.00   2.30 ± 0.44   8.57 ± 4.84   3.15 ± 1.72   7848 ± 1956   19.74 ± 1.13  
    0.16   2.28 ± 0.42   8.57 ± 3.68   3.01 ± 1.25   8920 ± 766   19.39 ± 1.67  
    0.33   1.48 ± 0.55   5.51 ± 2.24   2.56 ± 1.02   6422 ± 1934   19.22 ± 0.85  
    0.67   0.86 ± 0.27   6.46 ± 2.90   1.89 ± 2.02   9594 ± 1400   19.03 ± 1.50  
MDA-MB-231/LM2-4 (metastatic variant), Nvb      
    0   2.10 ± 0.54   18.20 ± 4.40   3.44 ± 2.68   6988 ± 2295   20.80 ± 0.95  
    3   1.88 ± 0.76   13.53 ± 2.72   2.11 ± 0.97   8844 ± 1135   22.15 ± 0.62  
    6   1.88 ± 0.48   9.15 ± 4.42*  4.76 ± 3.12   4986 ± 3870   22.40 ± 1.76  
    9   1.20 ± 0.62   6.24 ± 2.31  2.25 ± 1.01   4301 ± 1068   21.10 ± 1.16  
    12   1.18 ± 0.30   3.94 ± 1.68  1.98 ± 1.02   3317 ± 761*  19.70 ± 1.78  
Friend erythroleukemia, CTX      
    0   3.33 ± 0.35   5.98 ± 1.38   6.30 ± 1.83   4209 ± 1282   20.18 ± 1.25  
    10   2.96 ± 0.96   6.81 ± 1.20   6.80 ± 0.87   3345 ± 1035   19.05 ± 3.06  
    20   2.38 ± 0.77   5.70 ± 2.30   7.31 ± 2.73   3346 ± 1644   19.82 ± 0.75  
    50   1.65 ± 0.68   3.72 ± 1.81   5.07 ± 1.85   3150 ± 897   16.38 ± 2.27 
Friend erythroleukemia, CDDP      
    0.0   4.50 ± 1.02   9.42 ± 5.09   11.58 ± 1.90   3464 ± 1504   16.6 ± 0.37  
    0.5   3.74 ± 0.40   10.90 ± 10.56   9.66 ± 5.87   4108 ± 1503   16.9 ± 0.90  
    1.0   3.73 ± 1.41   7.67 ± 4.00   9.84 ± 3.66   6295 ± 1288   16.4 ± 1.04  
    2.0   3.88 ± 0.63   4.22 ± 1.27   8.10 ± 3.42   2794 ± 988   15.0 ± 0.89* 
    3.0
 
3.32 ± 1.30
 
6.17 ± 3.57
 
8.15 ± 3.24
 
3684 ± 1101
 
13.9 ± 1.50*
 

Tumor model (description), drug, and drug dose, mg/kg

Total WBC count, per μL PB

Neutrophil counts, per 104 PB cells

Lymphocyte counts, per 104 PB cells

Bone marrow proliferation, cpm/105 cells

Body weight, g
MeWo (human melanoma), CTX      
    0   4.06 ± 2.38   7.41 ± 4.13   11.29 ± 11.34   9563 ± 3045   24.46 ± 1.20  
    10   2.62 ± 0.65   7.23 ± 3.79   13.01 ± 5.70   12460 ± 3079   26.67 ± 0.94  
    20   1.24 ± 0.63   6.69 ± 3.20   5.99 ± 2.00   10776 ± 1949   25.85 ± 1.91  
    40   1.02 ± 0.22   4.02 ± 1.78   6.93 ± 3.36   8844 ± 372   24.09 ± 2.56  
    50   0.76 ± 0.42   2.00 ± 1.38*  6.17 ± 4.52   6359 ± 1908   22.61 ± 1.03  
MDA-MB-231/MVB9 (human breast cancer, resistant to Vbl), Vbl      
    0.00   2.30 ± 0.44   8.57 ± 4.84   3.15 ± 1.72   7848 ± 1956   19.74 ± 1.13  
    0.16   2.28 ± 0.42   8.57 ± 3.68   3.01 ± 1.25   8920 ± 766   19.39 ± 1.67  
    0.33   1.48 ± 0.55   5.51 ± 2.24   2.56 ± 1.02   6422 ± 1934   19.22 ± 0.85  
    0.67   0.86 ± 0.27   6.46 ± 2.90   1.89 ± 2.02   9594 ± 1400   19.03 ± 1.50  
MDA-MB-231/LM2-4 (metastatic variant), Nvb      
    0   2.10 ± 0.54   18.20 ± 4.40   3.44 ± 2.68   6988 ± 2295   20.80 ± 0.95  
    3   1.88 ± 0.76   13.53 ± 2.72   2.11 ± 0.97   8844 ± 1135   22.15 ± 0.62  
    6   1.88 ± 0.48   9.15 ± 4.42*  4.76 ± 3.12   4986 ± 3870   22.40 ± 1.76  
    9   1.20 ± 0.62   6.24 ± 2.31  2.25 ± 1.01   4301 ± 1068   21.10 ± 1.16  
    12   1.18 ± 0.30   3.94 ± 1.68  1.98 ± 1.02   3317 ± 761*  19.70 ± 1.78  
Friend erythroleukemia, CTX      
    0   3.33 ± 0.35   5.98 ± 1.38   6.30 ± 1.83   4209 ± 1282   20.18 ± 1.25  
    10   2.96 ± 0.96   6.81 ± 1.20   6.80 ± 0.87   3345 ± 1035   19.05 ± 3.06  
    20   2.38 ± 0.77   5.70 ± 2.30   7.31 ± 2.73   3346 ± 1644   19.82 ± 0.75  
    50   1.65 ± 0.68   3.72 ± 1.81   5.07 ± 1.85   3150 ± 897   16.38 ± 2.27 
Friend erythroleukemia, CDDP      
    0.0   4.50 ± 1.02   9.42 ± 5.09   11.58 ± 1.90   3464 ± 1504   16.6 ± 0.37  
    0.5   3.74 ± 0.40   10.90 ± 10.56   9.66 ± 5.87   4108 ± 1503   16.9 ± 0.90  
    1.0   3.73 ± 1.41   7.67 ± 4.00   9.84 ± 3.66   6295 ± 1288   16.4 ± 1.04  
    2.0   3.88 ± 0.63   4.22 ± 1.27   8.10 ± 3.42   2794 ± 988   15.0 ± 0.89* 
    3.0
 
3.32 ± 1.30
 
6.17 ± 3.57
 
8.15 ± 3.24
 
3684 ± 1101
 
13.9 ± 1.50*
 

Solid and erythroleukemia tumor models were treated with CTX administered through the drinking water on a daily basis, Vlb by intraperitoneal injection 3 times a week, Nvb by oral gavage 3 times a week, and CDDP by intraperitoneal injection twice a week at the indicated doses. Measurements (values are present as mean ± SD) of total WBC, neutrophil, and lymphocyte counts and bone marrow proliferation were performed 1 week after the initiation of treatment, as described in “Study design.” Body weights of all animals were monitored on a weekly basis. Body weight represents mean ± SD after 3 weeks of treatment.

*

Significant differences from control for .05 > P > .01.

Significant differences from control are indicated for P < .01.

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