Figure 5. Effect of erlotinib with cisplatin on tumor regrowth of xenografts.

(A) Mice were subcutaneously implanted with SQ20B cells. When tumors reached a size of ∼5 mm in diameter, therapy was started. One group of mice (five mice) received a single dose of cisplatin (CDDP) intraperitoneally (1 mg/kg). Three hours later, the mice were sacrificed, and tumors were removed and snap frozen in liquid nitrogen. The second group of mice was fed an erlotinib-containing diet, and then on day 5 the mice were injected with CDDP intraperitoneally (1 mg/kg). Three hours later, the mice were sacrificed, and tumors were removed and snap frozen in liquid nitrogen. (B) Mice were subcutaneously implanted with SQ20B cells. When tumors reached a size of ∼5 mm in diameter, therapy was started. One quarter of the mice received no therapy (control). One quarter received a single dose of cisplatin (CDDP) intraperitoneally (1 mg/kg) on Day 1. One quarter received erlotinib feed on days 1 through 4 and the morning of day 5 followed by a single dose of CDDP on day 5. One quarter received erlotinib feed starting on day 1 and continuing through the morning of day 5 but no CDDP. Erlotinib was not given from day 6 onward for any group. (C) Test of synergy for regrowth delay in time to reach tumor volume of 2,000 mm³ (D) Mice were subcutaneously implanted with SQ20B cells. When tumors reached ∼5 mm in diameter, a third of the mice were given a single injection of CDDP (on Day 1) then later that day started on an erlotinib-containing diet that continued through day 5. A third of the mice were given erlotinib feed on days 1 through 4 and the morning of day 5 followed by a single dose of CDDP on day 5. Erlotinib was not given from day 6 onward for any group. A third received no therapy (control). Mean tumor volume±standard deviation of time to reach 1,250 mm³ were 16.5±3.21, 17.1±4.22 and 26.0±6.40 days for control, CDDP ->erlotinib, erlotinib ->CDDP groups respectively. The three groups were significantly different (p = 0.0001; ANOVA) with the erlotinib ->CDDP group having a significantly longer time period as compared with both control (p = 0.003) and CDDP ->erlotinib (p = 0.006) groups.