Treatment of refractory tumors using epothilone derivatives

A method for treating a tumor in a mammal, said tumor having demonstrated resistance to oncology therapy, comprising administering to said mammal an effective amount of a composition comprising a pharmaceutically acceptable carrier and an epothilone compound of formula:

• wherein:
• Q is selected from the group consisting of
• G is selected from the group consisting of alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo,
• W is O or NR15;
• X is O or H, H;
• Y is selected from the group consisting of O;
• H, OR16;
• OR17, OR17;
• NOR18;
• H, NHOR19;
• H, NR20R21;
• H, H;
• and CHR22;
• wherein OR17, OR17 can be a cyclic ketal;
• each Z1 and Z2 is, independently, selected from the group consisting of CH2, O, NR23, S, and SO2, wherein only one of Z1 and Z2 can be a heteroatom;
• each B1 and B2 is, independently, selected from the group consisting of OR24, OCOR25, and O—C(═O)—NR26R27, and when B1 is H and Y is OH, H, they can form a six-membered ring ketal or acetal;
• D is selected from the group consisting of NR28R29, NR30COR31 and saturated heterocycle;
• each R1, R2, R3, R4, R5, R6, R7, R13, R14, R18, R19, R20, R21, R22, R26 and R27 is, independently, selected from the group consisting of H, alkyl, substituted alkyl, and aryl, and when R1 and R2 are alkyl can be joined to form a cycloalkyl, and when R3 and R4 are alkyl can be joined to form a cycloalkyl;
• each R9, R10, R16, R17, R24, R25 and R31 is, independently, selected from the group consisting of H, alkyl, and substituted alkyl;
• each R8, R11, R12, R28, R30, R32, and R33 is, independently, selected from the group consisting of H, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl and heterocyclo;
• and
• each R15, R23 and R29 is, independently, selected from the group consisting of H, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, heterocyclo, R32C═O, R33SO2, hydroxy, O-alkyl or O-substituted alkyl;
• and pharmaceutically acceptable salts thereof and any hydrates, solvates or geometric, optical and stereoisomers thereof,
• with the proviso that compounds wherein W and X are both O;
• R1, R2 and R7 are H;
• R3 R4 and R6 are methyl;
• R8 is H or methyl;
• Z1 and Z2 are CH2;
• G is 1-methyl-2-(substituted-4-thiazolyl)ethenyl;
• and Q is as defined above, are excluded.