Combination therapy with an antitumor alkaloid

Abstract

The present invention relates to the combination of PM01183 with several anticancer drugs, in particular other anticancer drugs selected from antitumor platinum coordination complexes, antimetabolites, mitotic inhibitors, anticancer antibiotics, topoisomerase I and/or II inhibitors, proteasome inhibitors, histone deacetylase inhibitors, nitrogen mustard alkylating agents, nitrosourea alkylating agents, nonclassical alkylating agents, estrogen antagonists, androgen antagonists, mTOR inhibitors, tyrosine kinase inhibitors, and other agents selected from aplidine, ET-743, PM02734 and PM00104, and the use of these combinations in the treatment of cancer.

What is claimed is: 
     
         1 . A method of treating cancer comprising administering to a patient in need of such treatment PM01183, or a pharmaceutically acceptable salt thereof, and an anticancer antibiotic, wherein the amounts of PM01183 and the anticancer antibiotic when administered in combination are therapeutic. 
     
     
         2 . The method of treating cancer according to  claim 1 , wherein the PM01183 and the cancer antibiotic are administered in synergistic amounts. 
     
     
         3 . The method of treating cancer according to  claim 1 , wherein the cancer to be treated is selected from the group consisting of lung cancer, sarcoma, malignant melanoma, bladder carcinoma, prostate cancer, pancreas carcinoma, thyroid cancer, gastric carcinoma, ovarian cancer, hepatoma, breast cancer, colorectal cancer, kidney cancer, esophageal cancer, neuroblastoma, brain cancer, cervical cancer, anal cancer, testicular cancer, leukemia, multiple myeloma and lymphoma. 
     
     
         4 . The method of treating cancer according to  claim 3 , wherein the cancer to be treated is selected from the group consisting of lung cancer, sarcoma, malignant melanoma, prostate cancer, pancreas carcinoma, gastric carcinoma, ovarian cancer, hepatoma, breast cancer, colorectal cancer, kidney cancer, brain cancer, leukemia and lymphoma. 
     
     
         5 . The method of treating cancer according to  claim 1 , wherein PM01183, or a pharmaceutically acceptable salt thereof, and the anticancer antibiotic form part of the same medicament. 
     
     
         6 . The method of treating cancer according to  claim 1 , wherein PM01183, or a pharmaceutically acceptable salt thereof, and the anticancer antibiotic are provided as separate medicaments for administration at the same time or at different times. 
     
     
         7 . The method of treating cancer according to  claim 6 , wherein PM01183, or a pharmaceutically acceptable salt thereof, and the anticancer antibiotic are provided as separate medicaments for administration at different times. 
     
     
         8 . The method of treating cancer according to  claim 1 , wherein the anticancer antibiotic is selected from the group consisting of daunorubicin, doxorubicin, epirubicin, idarubicin, mitoxantrone, pixantrone, valrubicin, mitomycin C, bleomycin, actinomycin D and mithramycin. 
     
     
         9 . The method of treating cancer according to  claim 8 , wherein the anticancer antibiotic is selected from the group consisting of daunorubicin, doxorubicin, mitomycin C and actinomycin D. 
     
     
         10 . The method of treating cancer according to  claim 9 , wherein the anticancer antibiotic is doxorubicin. 
     
     
         11 . The method of treating cancer according to  claim 10 , wherein the combination of PM01183 and doxorubicin is synergistic. 
     
     
         12 . A method of increasing the therapeutic efficacy of an anticancer antibiotic in the treatment of cancer, which comprises administering to a patient in need thereof PM01183, or a pharmaceutically acceptable salt thereof, in conjunction with said anticancer antibiotic, wherein the amounts of the PM01183 and the anticancer antibiotic when administered in combination are therapeutic. 
     
     
         13 . The method of increasing the therapeutic efficacy of an anticancer antibiotic in the treatment of cancer according to  claim 12 , wherein the PM01183 and the anticancer antibiotic are administered in synergistic amounts. 
     
     
         14 . The method of increasing the therapeutic efficacy of an anticancer antibiotic in the treatment of cancer according to  claim 12 , wherein the cancer to be treated is selected from the group consisting of lung cancer, sarcoma, malignant melanoma, bladder carcinoma, prostate cancer, pancreas carcinoma, thyroid cancer, gastric carcinoma, ovarian cancer, hepatoma, breast cancer, colorectal cancer, kidney cancer, esophageal cancer, neuroblastoma, brain cancer, cervical cancer, anal cancer, testicular cancer, leukemia, multiple myeloma and lymphoma. 
     
     
         15 . The method of increasing the therapeutic efficacy of an anticancer antibiotic in the treatment of cancer according to  claim 14 , wherein the cancer to be treated is selected from the group consisting of lung cancer, sarcoma, malignant melanoma, prostate cancer, pancreas carcinoma, gastric carcinoma, ovarian cancer, hepatoma, breast cancer, colorectal cancer, kidney cancer, brain cancer, leukemia and lymphoma. 
     
     
         16 . The method of increasing the therapeutic efficacy of an anticancer antibiotic in the treatment of cancer according to  claim 12 , wherein PM01183, or a pharmaceutically acceptable salt thereof, and the anticancer antibiotic form part of the same medicament. 
     
     
         17 . The method of increasing the therapeutic efficacy of an anticancer antibiotic in the treatment of cancer according to  claim 12 , wherein PM01183, or a pharmaceutically acceptable salt thereof, and the anticancer antibiotic are provided as separate medicaments for administration at the same time or at different times. 
     
     
         18 . The method of increasing the therapeutic efficacy of an anticancer antibiotic in the treatment of cancer according to  claim 17 , wherein PM01183, or a pharmaceutically acceptable salt thereof, and the anticancer antibiotic are provided as separate medicaments for administration at different times. 
     
     
         19 . The method of increasing the therapeutic efficacy of an anticancer antibiotic in the treatment of cancer according to  claim 15 , wherein the anticancer antibiotic is selected from the group consisting of daunorubicin, doxorubicin, epirubicin, idarubicin, mitoxantrone, pixantrone, valrubicin, mitomycin C, bleomycin, actinomycin D and mithramycin. 
     
     
         20 . The method of increasing the therapeutic efficacy of an anticancer antibiotic in the treatment of cancer according to  claim 25 , wherein the anticancer antibiotic is selected from the group consisting of daunorubicin, doxorubicin, mitomycin C and actinomycin D. 
     
     
         21 . The method of increasing the therapeutic efficacy of an anticancer antibiotic in the treatment of cancer according to  claim 20 , wherein the anticancer antibiotic is doxorubicin. 
     
     
         22 . The method of increasing the therapeutic efficacy of an anticancer antibiotic in the treatment of cancer according to  claim 21 , wherein the combination of PM01183 and doxorubicin is synergistic. 
     
     
         23 . A kit for use in the treatment of cancer which comprises a dosage form of PM01183, or a pharmaceutically acceptable salt thereof, a dosage form of an anticancer antibiotic, and instructions for the use of both drugs in combination. 
     
     
         24 . The kit according to  claim 23 , wherein the anticancer antibiotic is selected from the group consisting of daunorubicin, doxorubicin, epirubicin, idarubicin, mitoxantrone, pixantrone, valrubicin, mitomycin C, bleomycin, actinomycin D and mithramycin. 
     
     
         25 . The kit according to  claim 24 , wherein the anticancer antibiotic is selected from the group consisting of daunorubicin, doxorubicin, mitomycin C and actinomycin D. 
     
     
         26 . The kit according to  claim 25 , wherein anticancer antibiotic is doxorubicin.