Methods for modulating tumor growth and metastasis

Abstract

Methods and pharmaceutical compositions for modulating tumor growth or metastasis are provided.

Description

[0001] This application claims priority to U.S. Provisional Application 60 / 258,195, filed Dec. 22, 2000, entitled “Methods For Modulating Tumor Growth and Metastasis”.FIELD OF THE INVENTION [0002] This invention relates to the fields of oncology and improved chemotherapy regimens. BACKGROUND OF THE INVENTION [0003] The disclosure of each literature article and published patent document referred to herein is incorporated by reference herein in its entirety. [0004] Cellular transformation during the development of cancer involves multiple alterations in the normal pattern of cell growth regulation. Primary events in the process of carcinogenesis involve the activation of oncogene function by some means (e.g., amplification, mutation, chromosomal rearrangement), and in many cases, the removal of anti-oncogene function. In the most malignant and untreatable tumors, normal restraints on cell growth are completely lost as transformed cells escape from their primary sites and metastasize t...

AI Technical Summary

Benefits of technology

[0012] The present invention provides effective therapeutic methods for modulating tumor growth or metastasis wherein a combination of agents is employed. The methods of the present invention provide advantages such as greater overall efficacy, for example, in achieving synergy or avoiding antagonism, and allow, where desired, a reduction in the amount of one or more of the individual agents employed with a concomitant reduction in side effects. Further, where the tumor to be treated is not optimally responsive to a given anticancer agent, use of the present combination therapy methods can nonetheless provide effective treatment.

[0013] In particular, the present invention provides a method for modulating tumor growth or metastasis in an animal, especially a human, in need thereof, comprising sequential or simultaneous administration of a combretastatin A-4 compound or combretastatin A-1 compound and at least one other anticancer agent, in amounts effective therefor. Preferred such agents are described further below. The method of the present invention can provide the aforementioned advantages.

[0014] Further, the present inventors have found that certain sequences of administering the combretastatin A-4 compound or combretastatin A-1 compound and the other anticancer agent can, in vivo, potentiate the overall efficacy of the combination. Combretastatin A-4 compounds or combretastatin A-1 compounds, as antivascular agents, modulate blood flow to tumor tissue. By timing the administration of the combretastatin A-4 compound or combretastatin A-1 compound to modulate the flow of blood to the tumor to provide a time-dependent effective tumor concentration of the other anticancer agent, the overall efficacy of the combination is potentiated.

Problems solved by technology

Unfortunately, deleterious side effects are associated with each of these agents.

Administration of fluorouracil has also been associated with fever, chills, cough, sore throat, lower back pain, mouth sores, nausea, vomiting, pain and / or difficulty passing urine.

In particular, a number of studies have shown that administration of combretastatin A-4 disodium salt or combretastatin A-1 phosphate disodium salt causes an extensive shut-down of blood flow to the tumor vasculature, leading to secondary tumor cell death.

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