Method of tumor treatment
AssigneeThe Board of Trustees of the Leland Stanford Jr. Univ.
InventorJ. Martin Brown
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Abstract
The present invention provides methods for treating mammalian cancer tumors, preferably solid tumors, comprising administering to a mammal in need of such treatment an effective amount of a 1,2,4-benzotriazine oxide as defined in Formula I or pharmacologically acceptable salts of said compound; and administering to the mammal from about one half hour to about twenty-four hours after administering the 1,2,4-benzotriazine oxide an effective amount of a chemotherapy agent to which the minor is susceptible. The invention also provides kits for treatment of such tumors which comprise a chemotherapy agent and a cytotoxicity-enhancing amount of a 1,2,4-benzotriazine oxide as defined in Formula I.
Claims12
A method of treating a mammal having a solid tumor, said mammal in need of such treatment, comprising
- (a) administering to said mammal an effective amount of a compound having the formula ##STR26## wherein X is NH.sub.2 ;
- n is 0 or 1;
- and
- Y.sup.1 and Y.sup.2 are independently either H;
- nitro;
- halogen;
- hydrocarbyl (1-14C) including cyclic and unsaturated hydrocarbyl, optionally substituted with 1 or 2 substituents selected from the group consisting of halogen, hydroxy, epoxy, alkoxy (1-4C), alkylthio (1-4C), primary amine (NH.sub.2), alkyl (1-4C) secondary amine, dialkyl (1-4C) tertiary amino, dialkyl (1-4C) tertiary amine where the two alkyls are linked together to produce a morpholino, pyrrolidino or piperidino, acyloxy (1-4C), acylamido (1-4C) and thio analogs thereof, acetylaminoalkyl (1-4C), carboxy, alkoxycarbonyl (1-4C), carbamyl, alkylcarbamyl (1-4C), alkylsulfonyl (1-4C) or alkylphosphonyl (1-4C), wherein the hydrocarbyl can optionally be interrupted by a single ether (--O--) linkage;
- or wherein Y.sup.1 and Y.sup.2 are independently either morpholino, pyrrolidino, piperidino, NH.sub.2, NHR', NR'R'O(CO)R', NH(CO)R', O(SO)R', or O(POR')R' in which R' is a hydrocarbyl (1-4C) which may be substituted with OH, NH.sub.2, alkyl (1-4C) secondary amino, dialkyl (1-4C) tertiary amine, morpholino, pyrrolidino, piperidino, alkoxy (1-4C), or halogen substituents, or pharmacologically acceptable salt of said compound;
- and
- (b) administering to said mammal, from about one half hour to about twenty-four hours after administering said compound, an effective amount of carboplatin wherein a synergistic effect is derived from the administration of said compound and said carboplatin.
A method of increasing the cytotoxicity of carboplatin towards a solid tumor, said tumor susceptible to treatment with said carboplatin, comprising administering to a mammal having such a tumor, from about one hour to about two hours after administering said carboplatin or from about one half hour to about twenty-four hours prior to administering said carboplatin, a cytotoxicity-enhancing amount of a compound having the formula ##STR27## wherein X is NH.sub.2 ;
- n is 0 or 1;
- and
- Y.sup.1 and Y.sup.2 are independently either H;
- nitro;
- halogen;
- hydrocarbyl (1-14C) including cyclic and unsaturated hydrocarbyl, optionally substituted with 1 or 2 substituents selected from the group consisting of halogen, hydroxy, epoxy, alkoxy (1-4C), alkylthio (1-4C), primary amino (NH.sub.2), alkyl (1-4C) secondary amino, dialkyl (1-4C) tertiary amino, dialkyl (1-4C) tertiary amino where the two alkyls are linked together to produce a morpholino, pyrrolidino or piperidino, acyloxy (1-4C), acylamido (1-4C) and thio analogs thereof, acetylaminoalkyl (1-4C), carboxy, alkoxycarbonyl (1-4C), carbamyl, alkylcarbamyl (1-4C), alkylsulfonyl (1-4C) or alkylphosphonyl (1-4C), wherein the hydrocarbyl can optionally be interrupted by a single ether (--O--) linkage;
- or wherein Y.sup.1 and Y.sup.2 are independently either morpholino, pyrrolidino, piperidino, NH.sub.2, NHR', NR'R'O(CO)R', NH(CO)R', O(SO)R', or O(POR')R' in which R' is a hydrocarbyl (1-4C) which may be substituted with OH, NH.sub.2, alkyl (1-4C) secondary amino, dialkyl (1-4C) tertiary amino, morpholino, pyrrolidino, piperidino, alkoxy (1-4C), or halogen substituents, or pharmacologically acceptable salt of said compound wherein a synergistic effect is derived from the administration of said carboplatin and said compound.
Dependencies are inferred from the claim text.