FL118 shows improved efficacy in two in vivo models of irinotecan-resistant cancer in comparison with irinotecan. SCID mice bearing HCT116-SN50 or H460 subcutaneous xenografts with an average volume of ~100 mm3 were treated via IP once per week with 100 mg/kg irinotecan or 1.5 mg/kg FL118, on a repeating treatment for 4 weeks followed by 1 week of rest. Individual animals were considered to have progressed and were removed from treatment as tumor volume reached 1500 mm3 or for a moribund condition. A and B, tumor growth curves for HCT116-SN50 (A) and H460 (B) xenografts during treatment with either FL118 or irinotecan. As individual mice progressed and were removed from treatment, their final tumor volume was included in the graphed average on subsequent dates. Each treatment is indicated with a caret. C and D, Kaplan-Meier chart of progression events for animals with HCT116-SN50 (C) and H460 (D) xenografts. Statistical difference in time to progression between the two treatments was determined using the log-rank test. E and F, average body weight over time during treatments. Error bars = SEM.