Compositions and methods for the treatment of primary and metastatic neoplastic diseases using arsenic compounds

Abstract

The invention relates to the use of arsenic compounds to treat a variety of neoplastic diseases. The present invention encompasses the administration to a mammal of arsenic in the form of a salt, complex, organic compound or ionic solution to treat tumors of epithelial tissue, connective tissue, central nervous system, lymphoid tissue, hematopoietic cells and tumors associated with oncogenic viruses. This invention also encompasses the treatment of hematopoietic disorders in mammals by the administration of one or more arsenic compounds to said mammal. Further, the arsenic compounds may be used to treat metastatic neoplastic diseases.

We claim:  
     
         1 . A method of treating cancer in a human, which comprises administering to the human a combination of (i) a therapeutically effective amount of one or more arsenic compounds, and (ii) all trans-retinoic acid.  
     
     
         2 . The method of  claim 1 , wherein the arsenic compound is arsenic trioxide.  
     
     
         3 . The method of  claim 2 , wherein the arsenic trioxide is formulated as an ionic aqueous solution.  
     
     
         4 . The method of  claim 1 , wherein the total daily amount administered of the arsenic compound is from about 10 g to about 200 mg.  
     
     
         5 . The method of  claim 1 , wherein the total daily amount administered of the arsenic compound is from about 0.5 mg to about 150 mg.  
     
     
         6 . The method of  claim 1 , wherein the total daily amount administered of the arsenic compound is from about 0.5 mg to about 70 mg.  
     
     
         7 . The method of  claim 1 , wherein the arsenic compound is administered parenterally.  
     
     
         8 . The method of  claim 1 , wherein the arsenic compound is administered intravenously.  
     
     
         9 . The method of  claim 1 , wherein the all trans retinoic acid and the arsenic compound are administered in combination with an effective amount of at least one further therapeutic agent.  
     
     
         10 . The method of  claim 9 , wherein the further therapeutic agent is a chemotherapeutic or radiotherapeutic.  
     
     
         11 . The method of  claim 9 , wherein the further therapeutic agent is selected from the group consisting of etoposide, cisplatin, carboplatin, estramustine phosphate, vinblastine, methotrexate, hydroxyurea, cyclophosphamide, doxorubicin, 5-fluorouracil, taxol, diethylstilbestrol, VM-26(vumon), BCNU, procarbazine, cytokines, therapeutic vaccines, and immunomodulators.  
     
     
         12 . The method of  claim 2 , wherein the dose of the arsenic trioxide is varied according to the body weight of the human.  
     
     
         13 . The method of  claim 2 , wherein the cancer is a hematopoietic cancer.  
     
     
         14 . The method of  claim 2 , wherein the cancer is a leukemia.  
     
     
         15 . The method of  claim 14 , wherein the leukemia is an acute myelogenous leukemia.  
     
     
         16 . The method of  claim 15 , wherein the acute myelogenous leukemia is acute promyelogenous leukemia.  
     
     
         17 . The method of  claim 14 , wherein the leukemia is a chronic myelogenous leukemia.  
     
     
         18 . The method of  claim 2 , wherein the cancer is a lymphoma.  
     
     
         19 . The method of  claim 2 , wherein the cancer is a solid tumor.  
     
     
         20 . The method of  claim 2 , wherein the cancer has metastisized.