Pharmaceutical combinations for the treatment of cancer

Abstract

In accordance with the present invention there is provided a pharmaceutical combination useful for the treatment of cancer comprising at least one active compound of formula (I): and at least one further therapeutic agent chosen from a nucleoside analogue and / or a chemotherapeutic agents; and, a method of treating a patient having cancer comprising at least one active compound of formula (I), as defined above, and at least one further therapeutic agent chosen from a nucleoside analogue and / or a chemotherapeutic agents.

Description

FIELD OF THE INVENTION The present invention relates to pharmaceutical combinations useful in the treatment of cancer. Particularly, the combinations of this invention relate to dioxolane nucleosides with at least one further therapeutic agent chosen from nucleoside analogues and / or chemotherapeutic agents. BACKGROUND OF THE INVENTION Cancer is the second leading cause of death in the United States. It is estimated that cancer is responsible for 30% of all deaths in the Western world. Lung, colorectal, breast and prostate cancers are the four biggest killers. Many nucleoside-analogues have been found to possess anticancer activity. It was reported in (Weitman et al Clinical Cancer Research (2000), 6(4), pp 1574-1578 and Giles et al Journal of Clinical Oncology (2001), 19(3), pp 762-771 and also Gourdeau et al Cancer Chemother. Pharmacol. (2001), 47(3), pp 236-240) that troxacitabine (β-L-dioxolane cytidine, β-L-OddC, Troxatyl™), a nucleoside analogue, has shown to have potent act...

AI Technical Summary

Benefits of technology

For advantageous effects of the combination of the compounds of formula (I) and the additional therapeutic agents, they may be administered over a wide ratio. In one embodiment, the ratio of the compounds of formula (I) to the additional therapeutic agents in the present invention is between 1:250 to 250:1. Preferably, the additional therapeutic agent is other than doxorubicin.

of the combination of the compounds of formula (I) and the additional therapeutic agents, they may be administered over a wide ratio. In one embodiment, the ratio of the compounds of formula (I) to the additional therapeutic agents in the present invention is between 1:250 to 250:1. Preferably, the additional therapeutic agent is other than doxorubicin.

In one embodiment, the ratio of the compounds of formula (I) to the additional therapeutic agents in the present invention is between 1:50 to 50:1. Preferably, the additional therapeutic agent is other than doxorubicin.

In one embodiment, the ratio of the compounds of formula (I) to the additional therapeutic agents in our invention is between 1:20 to 20:1. Preferably, the additional therapeutic agent is other than doxorubicin. In a further embodiment, one may use from about 1:1 to about 1:15 of compounds of the invention:second therapeutic agent. In a further embodiment, one may use from about 1:1 to about 1:10 of compounds of the invention:second therapeutic agent. In a further embodiment, one may use from about 1:1 to about 1:5 of compounds of the invention:second therapeutic agent. In a further embodiment, one may use from about 1:1 to about 1:3 of compounds of the invention:second therapeutic agent. Preferably, the additional therapeutic agent is other than doxorubicin. If a further therapeutic agent is added, ratios will be adjusted accordingly.

While it is possible that, for use in therapy, a compound of the invention may be administered as the raw chemical it is preferable to present the active ingredient as a pharmaceutical formulation. The invention thus further provides a pharmaceutical formulation comprising a compound of formula (I) or a pharmaceutically acceptable derivative thereof together with one or more pharmaceutically acceptable carriers therefor and, optionally, other therapeutic and / or prophylactic ingredients. The carrier(s) must be “acceptable” in the sense of being compatible with the other ingredients of the formulation and not deleterious to the recipient thereof.

Pharmaceutical formulations include those suitable for oral, rectal, nasal, topical (including buccal and sub-lingual), transdermal, vaginal or parenteral (including intramuscular, sub-cutaneous and intravenous) administration or in a form suitable for administration by inhalation or insufflation. The formulations may, where appropriate, be conveniently presented in discrete dosage units and may be prepared by any of the methods well known in the art of pharmacy. All methods include the step of bringing into association the active compound with liquid carriers or finely divided solid carriers or both and then, if necessary, shaping the product into the desired formulation.

Problems solved by technology

In addition, the current therapies fail to cure most cancers once they have recurred.

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