Combination of epothilone analogs and chemotherapeutic agents for the treatment of proliferative diseases

A method for the treatment of a proliferative disease which comprises administering to a mammalian specie in need thereof a therapeutically effective amount of (1) a compound of formula I and (2) at least one anti-proliferative agent,

• 9
• wherein:
• Q is selected from the group consisting of
• 10
• G is selected from the group consisting of alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo,
• 11
• W is O or N R15;
• 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;
• Z1, and Z2 are independently selected from the group consisting of CH2, O, NR23, S, and SO2, wherein only one of Z1, and Z2 can be a heteroatom;
• B1 and B2 are 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;
• R1, R2, R3, R4, R5, R6, R7, R13, R14, R18, R19, R20, R21, R22, R26 and R27 are 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;
• R9, R10, R16, R17, R24, R25 and R31 are independently selected from the group consisting of H, alkyl, and substituted alkyl;
• R8, R11, R12, R28, R30, R32, and R33 are independently selected from the group consisting of H, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl and heterocyclo;
• R15, R23 and R29 are 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 steroisomers thereof, wherein said compound of formula I and said anti-proliferative agent are administered simultaneously or sequentially.