Use of protein kinase C inhibitors to enhance the clinical efficacy of oncolytic agents and radiation therapy

A method for treating a neoplastic condition sensitive to the combination below which comprises administering to a mammal in need of such treatment an effective amount of an oncolytic agent having an anti-neoplastic effect in combination with a protein kinase C inhibitor selective for a beta-1- or beta-2- isozyme of protein kinase C, wherein the protein kinase C inhibitor is administered in an amount sufficient to enhance the anti-neoplastic effect of the oncolytic agent, and wherein the protein kinase C inhibitor is a bis-indolylmalemide and has the following formula:

• wherein:
• R1 is
• R1′ is hydrogen, C1-C4 alkyl, aminoalkyl, monoalkylaminoalkyl, or dialkylaminoalkyl;
• R2 and R2′ are independently hydrogen, alkyl, alkoxyalkyl, hydroxyalkyl, C1-C3 alkylthio, S(O)C1-C3 alkyl, or CF3;
• R3 is hydrogen or CH3CO-;
• R4, R4′, R5, R5′, R6, R6′, R7 and R7′are independently hydrogen, halogen, alkyl, hydroxy, alkoxy, —COO(C1-C3 alkyl), CF3, nitro, amino, acetylamino, monoalkylamino, dialkylamino, alkylthio, C1-C3 alkylthio, or S(O)C1-C3 alkyl;
• R12 is hydrogen, alkyl, haloalkyl, cycloalkyl,acetyl, aryl, —CH(aryl)2, amino, monoalkylamino, dialkylamino, guaidino, —C(=N(alkoxycarbonyl))NH(alkyoxycarbonyl), amidino, hydroxy, carboxy, alkoxycarbonyl or heterocyclyl;
• p and q are independently 1, 2, 3, or 4;
• s is 0, 1, 2 or 3;
• t is 1 or 2;
• u is 0 or 1;
• or a pharmaceutically acceptable salt or solvate thereof.