Nude mice bearing human tumor xenograft is the most widely used model for evaluating new antitumor agents prior to the clinical trials. The terms of claims for “therapeutic effect”, “potent therapeutic effect”, or “curative effect” are vague since they are non-quantitative and they tend to be arbitrary. During the past 11 months, we have reported that a microtubule stabilizing agent, 26-trifluoro-9,10-dehydro-12,13-desoxyepothilone B (Fludelone) showed unprecedented antitumor effects against variety xenograft tumors in nude mice. These experiments, including the follow-up studies lasted as long as 300 days over the average nude mice life span of 2 yrs. We can now have a rare opportunity to classify antitumor effects with different stages and grades that were not attained before. When compared with the untreated control, the following staging/grading can be made: I. Tumor growth suppression (Ia, 1-50%; Ib, 50-90%; Ic, 90-99%). II. Tumor shrinkage (IIa, 1-50%; IIb, 50-90%; IIc, 90-99%). III. Tumor disappearance or remission (IIIa, relapse in 1 wk; IIIb, relapse in 1 wk-1 mon; IIIc, relapse in 1-3 mons) and IV. Cure or no relapse for over 3 mons (over 12.5% of lifespan). Using approximated xenograft tumor size doubling time in the untreated control group as a guide, one can estimate the log cell-kill in the treated group at a specific time point of remission. Thus, if doubling is 3 days and remission is 3 months, then 290/3= 230, which yields 9.03 log cell-kill. It is reasonable to expect a “cure” when cells are killed to less than one billionth that are left remaining. In the Fludelone experiment, MX-1 tumor was implanted on day 0, tumor xenograft reached 960mm-3 (3.4% of body weight) on D22, when treatment of Fludelone 25mg/kg Q3Dx5 6hr - iv infusion on D22, 25, 28, 31 and 34, and with consolidation treatment given on D43, 46, 49 and 52. The following results are obtained: Suppression, Ib (D25), Shrinkage, IIa (D28), IIb (D31-34), IIc (D37-49), Remission, IIIa (D52-58), IIIb (D59-81), IIIc (D82-142) and Cure, IV. (D142-240). These results marked the longest remission without a relapse and the longest follow-up studies than it has ever been recorded in experimental cancer therapeutics. The estimated log cell-kill was 2(240-51)/4 = 1.67x1014, that yielded > 14.22 log cell-kill. In another experiment using HCT-116 colon carcinoma xenograft, both Taxol and Fludelone at 20mg/kg, (Q2Dx4) x3, 6hr- iv infusion led to complete tumor remission whereas Taxol relapsed within 1.1 months (IIIc) but Fludelone cured the tumor without a relapse (IV) for over 7 mons in the 260 day experiment. Using these two xenograft models, some other cancer chemotherapeutic agents including bio-tech generated drugs, were also examined.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]