Compositions for the treatment of neoplasms

A method of treating a neoplasm in a human patient, said method comprising administering a composition comprising a compound of formula I and a compound of formula II, wherein a first plasma level of between 0.3 ng/mL and 3.5 μg/mL for said compound of formula I and a second plasma level of between 0.2 ng/mL and 2.5 μg/mL for said compound of formula II is maintained for at least 12 hours, wherein said compound of formula I is:

• or a pharmaceutically acceptable salt or prodrug thereof, wherein
• each of R1, R3, R4, R5, R6, R7, and R8 is, independently, H, OH, F, OCF3, or OCH3;
• R2 is selected from the group consisting of:
• CF3, halo, OCH3, COCH3, CN, OCF3, COCH2CH3, CO(CH2)2CH3, and SCH2CH3;
• R9 is selected from the group consisting of:
• R9 has the formula:
• wherein n is 0 or 1, Z is NR34R35 or OR36;
• each of R31, R32, R33, R34 R35, and R36 is, independently, H, C1-7 alkyl, C2-7 alkenyl, C2-7 alkynyl, C2-6 heterocyclyl, C6-12 aryl, C7-14 alkaryl, C3-10 alkheterocyclyl, acyl, or C1-7 heteroalkyl;
• or any of R32, R33, R34, R35, and R36 can be optionally taken together with intervening carbon or non-vicinal O, S, or N atoms to form one or more five- to seven-membered rings, optionally substituted by H, halogen, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C2-6 heterocyclyl, C6-12 aryl, C7-14 alkaryl, C3-10 alkheterocyclyl, acyl, or C1-7 heteroalkyl;
• and
• W is selected from the group consisting of:
• said compound of formula II is:
• or a pharmaceutically acceptable salt or prodrug thereof, wherein
• A is
• wherein each of X and Y is, independently, O, NR19, or S, each of R14 and R19 is, independently, H or C1-6 alkyl, each of R15, R16, R17, and R18 is, independently, H, C1-6 alkyl, halogen, C1-6 alkoxy, C6-18 aryloxy, or C6-18 aryl-C1-6 alkoxy, and p is an integer of 2 to 6;
• each of m and n is, independently, an integer of 0 to 2;
• each of R10 and R11 is
• wherein R21 is H, C1-6 alkyl, C3-8 cycloalkyl, C1-6 alkoxy-C1-6 alkyl, hydroxy C1-6 alkyl, C1-6 alkylamino-C1-6 alkyl, amino-C1-6 alkyl, or C6-18 aryl;
• R22 is H, C1-6 alkyl, C3-8 cycloalkyl, C1-6 alkoxy, C1-6 alkoxy-C1-6 alkyl, hydroxyl-C1-6 alkyl, C1-6 alkylamino-C1-6 alkyl, amino-C1-6 alkyl, carbo(C1-6 alkoxy), carbo(C6-18 aryl-C1-6 alkoxy), carbo(C6-18 aryloxy), or C6-C18 aryl;
• and R20 is H, OH, or C1-6 alkoxy, or R20 and R21 together represent
• wherein each of R23, R24, and R25 is, independently, H, C1-6 alkyl, halogen, or trifluoromethyl, each of R26, R27, R28, and R29 is, independently, H or C1-6 alkyl, and R30 is H, halogen, trifluoromethyl, OCF3, NO2, C1-6 alkyl, C3-8 cycloalkyl, C1-6 alkoxy, C1-6 alkoxy-C1-6 alkyl, hydroxyl-C1-6 alkyl, C1-6 alkylamino-C1-6 alkyl, amino-C1-6 alkyl, or C6-18 aryl;
• and
• each of R12 and R13 is, independently, H, Cl, Br, OH, OCH3, OCF3, NO2, and NH2, or R12 and R13 together form a single bond.