Therapeutic combination comprising a CDKS inhibitor and an antineoplastic agent
The present invention provides a therapeutic combination comprising (a) a compound of formula (I) as set forth in the specification and (b) one or more antineoplastic agents selected from the group consisting of alkylating or alkylating-like agents, antimetabolite agents and topoisomerase I inhibitors, wherein the active ingredients are present in each case in free form or in the form of a pharmaceutically acceptable salt or any hydrate thereof.
1. A therapeutic combination comprising (a) a compound of formula (I):
and (b) one or more antineoplastic agents selected from the group consisting of alkylating or alkylating-like agents, antimetabolite agents and topoisomerase I inhibitors, wherein the active ingredients are present in each case in free form or in the form of a pharmaceutically acceptable salt or any hydrate thereof.
2. A combination according to claim 1 wherein the alkylating or alkylating-like agent is selected from the group consisting of nitrogen mustards, aziridines, nitrosoureas, triazenes and platinum derivatives.
3. A combination according to claim 2 wherein the alkylating or alkylating-like agent is temozolomide, oxaliplatin or carboplatin.
4. A combination according to claim 1 wherein the antimetabolite agent is selected from the group consisting of 5-fluorouracil, capecitabine, gemcitabine, pemetrexed, methotrexate and edatrexate.
5. A combination according to claim 4 wherein the antimetabolite agent is 5-fluorouracil, gemcitabine or pemetrexed.
6. A combination according to claim 1 wherein the topoisomerase I inhibitor is selected from the group consisting of topotecan, irinotecan, SN-38 and 9-nitrocamptothecin.
7. A combination according to claim 6 wherein the topoisomerase I inhibitor is irinotecan or topotecan.
8. A combination according to claim 1 comprising the compound of formula (I) as defined in claim 1 , carboplatin and pemetrexed.
9. The combination according to claim 1 which is a combined preparation for simultaneous, separate or sequential use.
10. The combination according to claim 1 in a method of treating or delaying the progression of a proliferative disorder, wherein the said method comprises the simultaneous, sequential or separate administration to a subject in need thereof of the therapeutic combination.
11. A pharmaceutical composition comprising a combination according to claim 1 admixed with a pharmaceutically acceptable carrier, diluent or excipient.
12. A method of treating a proliferative disorder in a patient in need thereof, wherein said treatment comprises simultaneously, sequentially or separately administering to said patient a compound of formula (I) as defined in claim 1 and one or more antineoplastic agents selected from the group consisting of alkylating or alkylating-like agents, antimetabolite agents or topoisomerase I inhibitors.
13. A method for treating a proliferative disorder in a patient in need thereof, comprising administering to said patient a therapeutically effective amount of the compound of formula (I) as defined in claim 1 and one or more antineoplastic agents selected from the group consisting of alkylating or alkylating-like agents, antimetabolite agents or topoisomerase I inhibitors.
14. A method for lowering the side effects caused by antineoplastic therapy with an antineoplastic agent in mammals, including humans, in need thereof, the method comprising administering to said mammal a combined preparation comprising the compound of formula (I) according to claim 1 and one or more antineoplastic agents selected from the group consisting of alkylating or alkylating-like agents, antimetabolite agents and topoisomerase I inhibitors, in amounts effective to produce a synergic antineoplastic effect.
15. A commercial package comprising, in a suitable container mean, (a) a compound of formula (I) as defined in claim 1 , and (b) one or more antineoplastic agents selected from the group consisting of alkylating or alkylating-like agents, antimetabolite agents and topoisomerase I inhibitors wherein the active ingredients are present in each case in free form or in the form of a pharmaceutically acceptable salt or any hydrate thereof, together with instructions for simultaneous, separate or sequential use thereof.