TABLE 1

Antitumor efficacy evaluation of C1 and C2 against early-stage human R5 and HeLa in female SCID mice

The 8-week-old female NCR SCID mice were implanted bilaterally subcutaneously with 30- to 60-mg tumor fragments by a 12-gauge trocar on day 0. Both tumor studies (WT and R5 HeLa cells) used four mice per group. Median mouse body weights for each experiment were within 2 g and were 19 g (WT) or 19.5 g (R5) HeLa cells at the start of therapy. Chemotherapy was started on day 3 after tumor implantation, when the numbers of cells were small (10⁷–10⁸ cells). Day 0 is the day of tumor implant. Median tumor masses were determined (including zeros). To determine the T/C value, the treatment and control groups were measured when the control group tumors reached 1000 mg in size (median of group). T/C is an indication of antitumor effectiveness. T/C ≤42% is considered significant antitumor activity by the Drug Evaluation Branch of the Division of Cancer Treatment (National Cancer Institute). T/C <10% is considered to indicate highly significant antitumor activity and is the level used to justify a clinical trial if toxicity, formulation, and certain other requirements are met. T/C = 0 indicates very high antitumor activity. Statistical analyses were performed for the differences in T − C and log₁₀ kills between WT and R5 HeLa cells for C1 and C2 relative to the median control values for each tumor. Differences in T − C and log₁₀ kill results between R5 and WT HeLa cells for compound C1 were statistically significant (P = 0.014 and P = 0.0135, respectively). Whereas these parameters also differed for C2 between the cell lines, these differences did not quite reach statistical significance (P = 0.146).