Drug – bio-affecting and body treating compositions – Inorganic active ingredient containing – Heavy metal or compound thereof
Reexamination Certificate
2002-01-11
2003-07-22
Goldberg, Jerome D. (Department: 1614)
Drug, bio-affecting and body treating compositions
Inorganic active ingredient containing
Heavy metal or compound thereof
C514S449000, C514S517000
Reexamination Certificate
active
06596320
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to a method for treating patients afflicted with cancer, and will have application to a combination drug treatment possessed of fewer and less severe unwanted toxic adverse effects.
BACKGROUND OF THE INVENTION
Combination chemotherapy is a common, accepted treatment for many types of cancers. In many cases, the synergistic effects of combining two or more agents can be the difference between successful and unsuccessful treatment of the patient.
Many combination treatment regimens are well known in the oncology field. As an example, MOPP (an acronym for mechlorethamine, vincristine, procarbazine, prednisone) is a curative treatment regimen for Hodgkins' Disease. Several different combination regimens (which all include cisplatin, vinblastine and bleomycin) are accepted in the treatment of testicular cancer, which is curable in up to 98% of diagnosed cases. In all, more than 300 different combination regimens have been used.
The main drawback to combination chemotherapy is often that the synergy of action also applies to an increase in the severity, and even sometimes additional unwanted toxic effects. In addition, the schedule of administration of each drug in various combination regimens has, in many circumstance, been observed to result in greater toxicity. Particularly in cases where the preferred combination regimen includes the administration of paclitaxel followed by cisplatin, the combined effects of the two agents tends to cause dose-limiting neurotoxicity, nephrotoxicity and bone marrow suppression.
Another consideration of importance in combination chemotherapy is the sequence in which the antineoplastic agents are administered. For instance, where cisplatin and paclitaxel are administered as a part of a combination treatment regimen, it has been shown that due to severe toxicity considerations, paclitaxel must be administered first, followed by administration of cisplatin. If the order of administration is reversed, the combination is highly toxic to the patient. The anifestation of such severe schedule dependent toxicity recludes the administration of the cisplatin followed by aclitaxel combination because of the risk of serious oxicities, morbidity and even death. Currently, there is no method available to allow the safe and effective administration of cisplatin followed by paclitaxel in a combination regimen.
We have made the surprising discovery that the administration of a platinum compound (cisplatin) prior to the administration of a taxane (paclitaxel) results in at least additive antitumor activity in human cancer cells.
This invention may lead to increased antitumor activity in patients who are treated with a platinum drug followed by the administration of a taxane. The invention will allow such administration to be more safely accomplished in patients with cancer by the administration of an effective dose of a formula I compound, followed by the administration of a platinum drug, optionally followed by administration of formula I compound, definitively followed by the administration of a taxane and optionally followed by administration of formula I compound.
This new invention will result in increased antitumor activity by the sequential administration of platinum and a taxane and reduced toxicity due to the administration of a Cytoprotective agent.
Disodium 2,2′-dithiobis ethane sulfonate (also referred to in the literature as Dimesna and BNP7787) has been shown to reduce the unwanted toxic effects associated with the administration of single agent cisplatin, and of single agent paclitaxel in human patients. Dimesna is generally regarded as extremely safe and efficacious for these uses and others, and has been shown not to interfere with the cytotoxic effects of the antineoplastic agent(s) with which it is co-administered.
U.S. Pat. No. 5,919,816 and others, disclose the use of dimesna, mesna, and other related compounds to reduce the toxicity of many antineoplastic agents, as well as the toxicity of various anti-infective agents, anti-diabetic agents, and others. Other patents disclosing the use are found in the Information Disclosure Statement submitted with this application.
SUMMARY OF THE INVENTION
This invention relates to methods of treating patients with cancer by administering combination chemotherapy wherein effective amounts and schedules of administration of two or more antineoplastic agents are administered to the patient, together with a toxicity reducing amount of a protective agent of the following formula I:
R
1
—S—X
1
—R
2
;
(I)
wherein R
1
is hydrogen, C
1
-C
6
alkyl, or —S—X
2
—R
3
;
R
2
and R
3
are each individually sulfonate or phosphonate; and
X
1
and X
2
are each individually C
1
-C
6
alkyl, optionally substituted by one or more hydroxy, sulfhydryl or alkoxy moieties.
Preferred antineoplastic agents include platinum based chemotherapy drugs (cisplatin, carboplatin, oxaliplatin, and others) and taxanes (including, but not limited to paclitaxel, docetaxel), and/or epothilones, and or vinca alkaloids, and/or oxazaphosphorines or other agents used in the chemotherapy of cancer, though the method of this invention is contemplated as useful in any of a vast number of combination chemotherapy regimens.
Dosage amounts, order of administration, routes of administration, dosage schedules, and other factors are taken into consideration when implementing the method of this invention. Some preferred schedules are set forth in the description below.
Accordingly, it is an object of this invention to provide for an improved method of treating patients with cancer for the purpose of increasing tumor shrinkage, quality of life, patient survival and the cure rate of human cancers.
Another object of this invention is to provide a new method of treating patients with cancer through combination chemotherapy along with a toxicity-preventing agent.
Another object is to provide for novel, safer, more effective methods of treating patients with cancer.
Other objects will become apparent upon a reading of the following description.
REFERENCES:
patent: 5902610 (1999-05-01), Hausheer et al.
patent: 5919816 (1999-07-01), Hausheer et al.
Carter et al., Chemotheraoy of Cancer, second edition, John Wiley & Sons, NY, NY, (1981), pp 107-108.
BioNumerik Pharmaceuticals, Inc.
Dodd Thomas J.
Goldberg Jerome D.
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