Fig. 4: In vivo xenograft models show highly potent suppression of tumor growth with combined use of erlotonib and prednisone.
a, b Athymic mice were subcutaneously injected with 1 million A549 cells. After tumors became visible (200 mm3), mice were divided into eight groups (n = 8) and received the indicated treatment by oral gavage except Etanercept by Intraperitoneal injection. The dosages are: etanercept 3 mg/kg/day, erlotinib 100 mg/kg/day, thalidomide 150 mg/kg/day, Prednisone (PRDN) 5 mg/kg/day. The treatment lasted for 28 days, except for 4 mice in prednisone + erlotinib groups received drugs for around 6 months, while treatment was withdrawn from the other 4 mice in the same group. Tumor sizes were monitored every 4 days using a caliper. A and B are the same experiment with a different time range. c A549 xenograft tumors were allowed to grow to 1000 mm3 prior to starting treatment with control vehicle (n = 14), and a combination of prednisone 5 mg/kg/day plus erlotinib 100 mg/kg/day (n = 12). One mouse had to be sacrificed due to the tumor ulceration (slashed line). d A delayed start of prednisone. Twenty-four nude mice bearing A549 xenografts were divided into four groups (n = 6). Afatinib 25 mg/kg/day was given when tumors reaches 200 mm3. When tumors reach around 1500 mm3, prednisone 5 mg/kg/day was also given as indicated. e 12 mice bearing A549 xenografts received concurrent prednisone + erlotinib (doses same as above) from 200 mm3 to 500 mm3. Then, prednisone dose in 6 mice (n = 6) was reduced from 5 to 1 mg/kg/day, with erlotinib unchanged. f An EGFRwt PDX HCC4087, was implanted into NOD-SCID mice. After tumors reached 400 mm3, mice were divided into six groups and treated with indicated drugs using the same doses as above (n = 6). Treatments lasted for 28 days, except afatinib + prednisone (4 months). g A similar experiment (n = 8), using erlotinib. h A similar using H441 cells (n = 8). Tumor sizes are shown as mean volume ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, #p > 0.05 by repeated measures (RM) two-way ANOVA, adjusted by Bonferroni’s test. The statistical analysis was performed on Graphpad Prism 9.0.0. Source data are provided as a Source Data file. p = 0.04,0.006,1E−4,0.003,0.03 (a); 0.04,0.006,1E−4,0.002,0.003,0.03 (b); 2E−6 (c); 0.003,5E−4,0.006 (d); 0.57 (e); 0.002.0.001,5E−5 (f); 5E−7 (g), 0.003,0.002 (h).
