ANALOGUES OF ETOPOSIDE FOR THE TREATMENT OF TUMOURS
Compounds for treatment of a patient having a tumour that is metastatic and/or that reduces an organ function, wherein the compounds are of the general formula: wherein X is O, NH and S, wherein n is 0, 1 or 2, wherein R 1 and R 2 are H, methyl or ethyl, or together form a group CR 3 R 4 , and wherein R 3 and R 4 are H, methyl or ethyl.
1 . A method of treating a tumor that is metastatic and/or that reduces an organ function in a subject, wherein said method comprises administering to the subject a compound of formula (I)
wherein X is selected from the group consisting of O, NH and S,
n is 0, 1 or 2, and
R 1 and R 2 are independently selected from the group consisting of H, methyl, and ethyl, or together form a group CR 3 R 4 wherein R 3 and R 4 are independently selected from the group consisting of H, methyl and ethyl.
2 . The method of claim 1 , wherein said method comprises administering to a subject in need of such treatment a compound selected from the group consisting of
3 . The method of claim 1 , wherein the subject is a human.
4 . The method of claim 1 , wherein the tumor is resistant to treatment with a therapeutic protein or a chemotherapeutic drug exclusive of the compound of formula (I)
wherein X is selected from the group consisting of O, NH and S,
n is 0, 1 or 2, and
R 1 and R 2 are independently selected from the group consisting of H, methyl, and ethyl, or together form a group CR 3 R 4 wherein R 3 and R 4 are independently selected from the group consisting of H, methyl and ethyl.
5 . The method of claim 1 , wherein the tumor is a solid tumor.
6 . The method of claim 5 , wherein the tumor is selected from the group consisting of adenocarcinoma, hypopharynx cancer, lung cancer, diffuse large cell lymphoma, Burkitt's lymphoma, Hodgkin lymphoma, Non-Hodgkin lymphoma, histiocytic lymphoma, lymphatic lymphoma, acute T-cell leukemia, pre-B-acute lymphoblastic leukemia, gall bladder cancer, bile duct carcinoma, thymus carcinoma, urothelium carcinoma, testicular cancer, prostate cancer, bladder cancer, brain tumor, AIDS-related Kaposi's sarcoma, Ewing sarcoma, rhabdomyosarcoma, neuroblastoma, ovarian cancer, breast cancer, and unknown primary origin (CUP) syndrome.
7 . The method of claim 1 , wherein the treatment leads to a stagnation of tumor growth or a remission of the tumor.
8 . The method of claim 1 , wherein said tumor reduces an organ function.
9 . The method of claim 1 , wherein the tumor expresses at least one of CES1 and CES2.
10 . The method of claim 9 , wherein a fraction of CES1 and/or CES2 expressing cells of the tumor is 50% or higher.
11 . The method of claim 1 , further comprising administering to the subject a second therapeutic drug compound.