Treatment method for cancer

A method for the treatment of cancer cells susceptible of treatment by chemotherapy by a chemotherapeutic agent in a living animal, which comprises:

• (a) first administering to said animal a potent antagonist selective for intracellular histamine receptors in an amount sufficient to inhibit the binding of intracellular histamine in normal and malignant cells, said potent antagonist selective for intracellular histamine receptors being a diphenyl compound of the formula:
• ##STR5## wherein X and Y are each fluorine, chlorine or bromine, Z is an alkylene radical of 1 to 3 carbons or a .dbd.C.dbd.O group, or the phenyl groups are joined to form a tricyclic ring o and p are 0 or 1, R.sub.1 and R.sub.2 are each alkyl groups containing 1 to 3 carbon atoms or are joined together to form a hetero-ring with the nitrogen atom and n is 1, 2 or 3, or a pharmaceutically-acceptable salt thereof, and
• (b) following sufficient time to permit said inhibition of binding of intracellular histamine, subsequently administering to said animal at least one chemotherappeutic agent for the cancer cells in an amount toxic to said cancer cells,
• whereby an enhanced toxic effect on said cancer cells from said at least one chemotherapeutic agent is obtained while, depending on the dose of said intracellular histamine antagonist, adverse effect of such at least one chemotherapeutic agent on said normal cells is significantly ameliorated.

A method for the treatment of cancer cells susceptible of treatment by chemotherapy by a chemotherapeutic agent in a living animal, which comprises:

• (a) first administering to said animal at least one chemotherapeutic agent for the cancer cells in an amount toxic to said cancer cells,and then
• (b) subsequently administering over a period of up to about 72 hours following administration of said chemotherapeutic agent, a potent antagonist selective for intracellular histamine receptors in an amount sufficient to inhibit binding of intracellular histamine in normal cells, said potent antagonist selective for intracellular histamine being a diphenyl compound of the formula:
• ##STR8## wherein X and Y are each fluorine, chlorine or bromine, Z is an alkylene radical of 1 to 3 carbon atoms or .dbd.C.dbd.O, or the phenyl groups are joined to form a tricyclic ring, o and p are 0 or 1, R.sub.1, and R.sub.2 are each alkyl groups containing 1 to 3 carbon atoms or are joined together to form a hetero-ring with the nitrogen atom and n is 1, 2 or 3, or a pharmaceutically-acceptable salt thereof,
• whereby the side effects of the administration of the at least one chemotherapeutic agent are at least ameliorated.

A method for the treatment of cancer cells susceptible of treatment by chemotherapy by a chemotherapeutic agent in humans, which comprises:

• (a) first administering to said humans a potent antagonist selective for intracellular histamine receptors in an amount sufficient to inhibit binding of intracellular histamine in normal and malignant cells administered over a period of up to about 90 minutes, said potent antagonist selective for intracellular histamine receptors being at least one diphenyl compound of the formula:
• ##STR12## wherein X and Y are each fluorine, chlorine or bromine, Z is an alkylene radical of 1 to 3 carbons or a .dbd.C.dbd.O group, or the phenyl groups are joined to form a tricyclic ring o and p are 0 or 1, R.sub., and R.sub.2 are each alkyl groups containing 1 to 3 carbon atoms or are joined together to form a hetero-ring with the nitrogen atom and n is 1, 2 or 3, or a pharmaceutically-acceptable salt thereof,
• (b) following sufficient time to permit said inhibition of binding of intracellular histamine, subsequently administering to said human at least one chemotherapeutic agent specific for said tumor in an amount toxic to said tumor, and then
• (c) thereafter administering to said human said potent antagonist selective for intracellular histamine receptors in an amount sufficient to ameliorate adverse side effects of said at least one chemotherapeutic agent for a period of up to about 72 hours following administration of said chemotherapeutic agent.