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Combination comprising combretastatin and anticancer agentsRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), O-glycoside, , Nitrogen Containing Hetero Ring, Pyrimidines (including Hydrogenated) (e.g., Cytosine, Etc.)Combination comprising combretastatin and anticancer agents description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070149476, Combination comprising combretastatin and anticancer agents. Brief Patent Description - Full Patent Description - Patent Application Claims
[0001] This application is a continuation of U.S. application Ser. No. 10/995,998, filed Nov. 23, 2004, which is a continuation of U.S. application Ser. No. 10/097,926, filed Mar. 15, 2002, now U.S. Pat. No. 6,933,320, which claims priority to U.S. provisional Application No. 60/275,627, filed Mar. 15, 2001, all of which are incorporated herein by reference in their entirety. FIELD OF INVENTION [0002] The present invention relates to therapeutic combinations comprising a stilbene derivative and anticancer agents such as taxanes, alkylating agents, antimetabolites, vinca alkaloids, epidophylloptoxins, and antibiotics for the treatment for cancer. [0003] The invention relates to the treatment of cancers, more especially solid tumors, with associations of stilbene derivatives and other anticancer drugs and the use of such associations for an improved treatment against cancers, and to uses of these effective ingredients for the treatment (therapy), suppression, and amelioration of tumors, and the like. BACKGROUND OF THE INVENTION [0004] Today, a wide variety of chemotherapeutic agents are used for treatment, and suppression of tumors, especially malignant solid tumors. Although these agents may have a tumor reducing effect, it is often not possible for these known agents to effect a cure due to acquisition of resistance against the agent by the cancer, relapse of the tumors, and so on. Therefore, further superior antitumor agents are needed. [0005] While stilbene derivatives, having cis-stilbene as a fundamental skeleton, are known to exhibit strong mitosis inhibitory activities and cytotoxity, most stilbene derivatives are not yet available as pharmaceutical agents because of their low solubility in water. [0006] Recently, it has been discovered that certain stilbene derivatives having activity for inhibiting tubulin polymerization also have improved water solubility. These include the phosphorylated pro-drug of combretastatin-A4 (See U.S. Pat. No. 5,561,122), and the stilbene derivatives disclosed in U.S. Pat. No. 5,674,906. The clinical use of these stilbene derivatives is felt to be promising. However, more work is needed to improve the efficacy of these and other stilbene derivatives. [0007] It is an object of the present invention to develop a superior antitumor agent, specifically, to develop a pharmaceutical preparation capable of improving the efficacy of a stilbene derivative and, in particular, to develop and provide antitumor agents exhibiting superior safety and efficacy in treating malignant tumors. SUMMARY OF THE INVENTION [0008] It has been found that a stilbene derivative, administered together with another anticancer agent such as a taxane, an alkylating agent, an antimetabolite, an epidophylloptoxin, an antibiotic, a platinum compound, and a vinca alkaloid, exhibit improved therapeutic effects to inhibit tumor growth. [0009] Among substances which may be used in association or in combination with the stilbene derivative are taxanes such as taxol, taxotere or their analogues; alkylating agents such as cyclophosphamide, isosfamide, melphalan, hexamethylmelamine, thiotepa or dacarbazine; antimetabolites such as pyrimidine analogues, for instance 5-fluorouracil, cytarabine, capecitabine, and gemcitabine or its analogues such as 2-fluorodeoxycytidine; folic acid analogues such as methotrexate, idatrexate or trimetrexate; spindle poisons including vinca alkaloids such as vinblastine, vincristine, vinorelbine and vindesine, or their synthetic analogues such as navelbine, or estramustine and a taxoid; platinum compounds such as cisplatin; epipodophyllotoxins such as etoposide or teniposide; antibiotics such as daunorubicin, doxorubicin, bleomycin or mitomycin, enzymes such as L-asparaginase, topoisomerase inhibitors such as topotecan or pyridobenzoindole derivatives; and various agents such as procarbazine, mitoxantrone, and biological response modifiers or growth factor inhibitors such as interferons or interleukins. [0010] Taxanes such as taxol and taxotere and vinca alkaloids such as vincristine and vinblastine are considered antimicrotubule agents which interfere with cell division by disrupting the normal functionality of the cellular microtubules. Alkylating agents such as cyclophosphamide, isosfamide, melphalan, hexamethylmelamine, thiotepa or dacarbazine generally exert cytotoxic activity by alkylating DNA, thus directly interfering with the reproductive cycle of the cell. Antimetabolites exert cytotoxic activity by substituting fraudulent nucleotides into cellular DNA, thereby interrupting cell division or inhibiting enzymes which are necessary for DNA replication. Epidophyllotoxins such as etoposide and teniposide are topoisomerase inhibitors. Antibiotics, such as doxorubicin and daunorubicin, are also thought to work by inhibiting topoisomerase II. [0011] It has now been found that these various anticancer agents in combination with a stilbene derivative are especially effective in the treatment of many solid tumors. Among the effective stilbene derivatives is combretastatin A-4, and a derivative of the compound, (Z)-1-(3-amino-4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)ethane (Compound II). Both of these compounds exhibit strong mitosis inhibitory activities, cytotoxicity, and inhibit tubulin polymerization. [0012] Combretastatin A-4 has the following formula: [0013] Compound II has the following formula: [0014] These combretastatins are barely soluble in water and can be used in the form of a salt exemplified by hydrochloride, acetate, phosphate, methanesulfonate, and the aminoacid salt. [0015] The manufacture of stilbene derivatives which may be in the form of pharmaceutically acceptable salts, hydrates and solvates, and the manufacture of oral and/or parenteral pharmaceutical composition containing the above compound, its inert pharmaceutically acceptable carrier(s) and/or diluent(s), are disclosed in U.S. Pat. Nos. 5,525,632, 5,731,353 and 5,674,906. These patents, which are incorporated herein by reference, disclose that stilbene derivatives, including combretastatin, when used alone, have carcinostatic effects in vivo. [0016] It has recently been discovered that the combination of combretastatin and an anticancer agent selected from the group consisting of taxoids, alkylating agents, antimetabolites, vinca alkaloids, platinum compounds, epidophylloptoxins and antibiotics significantly reduces the development of tumor volume over what would be predicted from administration to tumor-infected mammals of each compound alone. [0017] Thus, the present invention is promising as providing a novel antitumor agent, for example, a chemotherapeutic drug against cancer (cancer chemotherapy agent), comprising two types of active ingredients, namely a stilbene derivative and another anticancer compound that can be administered simultaneously or separately. DETAILED DESCRIPTION OF THE INVENTION [0018] The present invention is directed to an antitumor agent comprising a stilbene derivative and an anticancer agent. [0019] The present invention also encompasses a combination therapy wherein the stilbene derivative and another anticancer agent are prepared as two separate pharmaceutical preparations and administered to a patient in need thereof, simultaneously, semi-simultaneously, separately or spaced out over time. [0020] The tumors against which the antitumor agents of the present invention are administered encompass all sorts of tumors occurring in an animal, especially in a human being. The antitumor agents of the present invention may be used for inhibiting proliferation of tumor cells. The antitumor agents of the present invention are pharmaceutical preparations wherein at least two compounds are used to cure, treat, or suppress tumors. Continue reading about Combination comprising combretastatin and anticancer agents... Full patent description for Combination comprising combretastatin and anticancer agents Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Combination comprising combretastatin and anticancer agents patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. 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