Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heavy metal containing doai
Reexamination Certificate
1995-06-07
2001-09-11
Goldberg, Jerome D. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heavy metal containing doai
C514S648000
Reexamination Certificate
active
06288111
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to the fields of medical oncology and the pharmacotherapy of human cancers. More specifically, the present invention relates to novel methods of treating cisplatin resistant or cisplatin non-resistant cancers using a combination of tamoxifen and cisplatin.
2. Description of the Related Art
The treatment of cancer patients with platinum coordination complex antineoplastic agents, such as cis-diamminedichloroplatinum (II) (cisplatin) has increased substantially in the last decade. Cisplatin is a antineoplastic agent that has proved useful in the treatment of multiple malignancies including testicular cancer, ovarian cancer, and small cell lung cancer. The mechanism of action is currently unknown but may be related to the ability of cisplatin to bind to DNA and form various types of inter- and intrastrand crosslinks that possibly interfere with both DNA and RNA synthesis.
Cancer patients eventually become resistant to treatment with platinum coordination complexes, such as cisplatin. If the patient dies of metastatic cancer, the cells of the metastatic foci are usually also characterized by their extreme resistance to single or combinations of the available chemotherapeutic drugs. In general, drug resistant tumors can be classified as temporary or permanent. The mechanism of resistance to cisplatin is unclear but may be related to decreased drug accumulation, elevation of intracellular concentrations of metallothioneines or glutathione which bind and inactivate cisplatin, or to decreased cisplatin-DNA adduct formation or repair.
Tamoxifen is an antiestrogen agent that has been used extensively in the treatment of women with breast cancer. The accepted mechanism of action of tamoxifen in breast cancer is via antagonism of the estrogen receptor leading to interference with estrogen induced cell growth.
One of the major problems in cancer therapy today is the ability of tumor cells to develop resistance to chemotherapeutic agents. This is particularly frustrating because a patient initially responds to the antineoplastic drug, such as cisplatin.
The prior art remains deficient in the absence of an efficient and efficacious method of preventing resistance or overcoming established resistance to platinum coordination complex anti-neoplastic agents. In addition, the prior art is deficient in the lack of an effective method of potentiating the cytotoxic effects of platinum coordination complex anti-neoplastic agents.
SUMMARY OF THE INVENTION
The present invention provides a novel composition of matter for the treatment of human cancers. In addition, the present invention provides novel methods of reducing and/or overcoming resistance to platinum chemotherapeutic agents.
The present invention demonstrates a novel pharmacodynamic effect of tamoxifen (TAM), namely the ability to delay the emergence of resistance to cisplatin or cis-diaminedichloroplatinum (DDP) for cell lines representative of 2 important types of human malignancy, melanoma and ovarian carcinoma. It has not previously been demonstrated that TAM could alter the processes that underlie the development of resistance.
In one embodiment of the present invention, there is provided a composition of matter for the treatment of non-melanoma cancers, wherein the composition comprises a platinum anti-neoplastic compound and tamoxifen, wherein the platinum anti-neoplastic compound and tamoxifen exert a synergistic anti-tumor effect on the non-melanoma cancer.
In another embodiment of the present invention, there is provided a method of treating a non-melanoma cancer comprising administering to an individual having a non-melanoma cancer, a pharmacological dose of a platinum anti-neoplastic compound and tamoxifen, wherein the platinum anti-neoplastic compound and tamoxifen exert a synergistic anti-tumor effect on the non-melanoma cancer.
In yet another embodiment of the present invention, there is provided method of reducing resistance to platinum anti-neoplastic compounds in an individual having a neoplastic disease comprising administering tamoxifen to an individual, wherein the individual is susceptible to developing resistance to platinum anti-neoplastic compounds.
In still yet another embodiment of the present invention, there is provided method of overcoming resistance to platinum anti-neoplastic agents in an individual having a neoplastic disease, comprising administering tamoxifen to the individual.
In still yet another embodiment of the present invention, there is provided a method of killing non-melanoma neoplastic cells in bone marrow, comprising the steps of removing bone marrow from an individual having a neoplastic disease; contacting said bone marrow with a cytocidally effective dose of a platinum containing antineoplastic compound and tamoxifen, and returning said contacted bone marrow to said individual.
Other and further objects, features and advantages will be apparent from the following descriptions of the presently preferred embodiments in the invention which are given for the purpose of disclosure and when taken in conjunction with the accompanying drawings.
REFERENCES:
Rakel, Conn's Current Therapy, W. B. Saunders Co.,Philadelphia, Pa.,p. 151, Apr. 1992.*
Harwett et al., Wow-Serial (1991) Clinical Oncology Society of Australia, Inc., p. 129. The Original Reference to Follow.
Howell Stephen B.
Mc Clay Edward F.
Adler Benjamin Aaron
Goldberg Jerome D.
Research Development Foundation
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