University of Rochester

University of New York

Therese K Schmalbach

Richard F Borch

A process for preventing or ameliorating the myelosuppression which can occur in a mammal such as a human cancer patient being treated with a platinum-free antineoplastic drug is provided, comprising administering an effective dosage of a dithiocarbamate compound to said mammal, preferably subsequent to administration of the cytotoxic drug.

Use of dithiocarbamates to treat myelosuppression

A process is provided for obtaining one or more bone marrow cell growth factors having granulocyte/macrophage progenitor cell colony stimulating activity, said process comprising: (a) adding to the culture medium of an in vitro, established bone marrow culture a growth factor-stimulating amount of a dithiocarbamate; (b) separating the said dithiocarbamate from the in vitro treated bone marrow culture, adding fresh culture medium to said in vitro treated bone marrow culture, and permitting the concentration of said growth factor or factors to increase in said fresh culture medium; and (c) isolating said growth factor or factors from said fresh culture medium.

Method for stimulating transplanted bone marrow cells

Method for stimulating production of bone marrow cell growth factors

Various types of biological treatments, including antineoplastic treatments with antineoplastic drugs, can result in damage to the blood-forming function of the bone marrow. This damage can be reversed, at least to some degree, with an effective amount (preferably an extremely low dose) of a pharmaceutically acceptable dithiocarbamic compound, including a compound of the formula R.sub.1 R.sub.2 NCSSM or R.sub.1 R.sub.2 NCSS-SCSNR.sup.3 R.sup.4, wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are the same or different aliphatic or cycloaliphatic or heterocycloaliphatic groups, unsubstituted or substituted by hydroxyl, or one of R.sup.1 and R.sup.2 and one of R.sup.3 and R.sup.4 can be H, or R.sup.1 and R.sup.2 or R.sup.3 and R.sup.4, taken together with the N atom upon which the pair of R groups is substituted, can be a 5- or 6-member N-heterocyclic ring which is aliphatic or aliphatic interrupted by a ring oxygen or second ring nitrogen, and M is H or one equivalent of a pharmaceutically acceptable cation, in which case the rest of the molecule is negatively charged. The dosage in mammals can range from about 0.001 to 30 mg/kg of body weight. For larger mammals, including humans, a typical dosage unit is less than 10 mg/kg, e.g. &lt;3 mg/kg. The dosage unit can be dissolved in a suitable pharmaceutically acceptable carrier (e.g. an aqueous medium) and is then preferably administered intravenously within 8 hours of the administration of the agent which can cause bone marrow damage. The extremely low dosages particularly preferred in this invention do not cause any significant side effects.

Use of dithiocarbamates to counteract myelosuppression

Various types of biological treatments, including antineoplastic treatments with antineoplastic drugs, can result in damage to the blood-forming function of the bone marrow. This damage can be reversed, at least to some degree, with an effective amount (preferably an extremely low dose) of a pharmaceutically acceptable dithiocarbamic compound, including a compound of the formula R.sub.1 R.sub.2 NCSSM or R.sub.1 R.sub.2 NCSS--SCSNR.sup.3 R.sup.4, wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are the same or different aliphatic or cycloaliphatic or heterocycloaliphatic groups, unsubstituted or substituted by hydroxyl, or one of R.sup.1 and R.sup.2 and one of R.sup.3 and R.sup.4 can be H, or R.sup.1 and R.sup.2 or R.sup.3 and R.sup.4, taken together with the N atom upon which the pair of R groups is substituted, can be a 5- or 6-member N-heterocyclic ring which is aliphatic or aliphatic interrupted by a ring oxygen or second ring nitrogen, and M is H or one equivalent of a pharmaceutically acceptable cation, in which case the rest of the molecule is negatively charged. The dosage in mammals can range from about 0.001 to 30 mg/kg of body weight. For larger mammals, including humans, a typical dosage unit is less than 10 mg/kg, e.g. &lt;3 mg/kg. The dosage unit can be dissolved in a suitable pharmaceutically acceptable carrier (e.g. an aqueous medium) and is then preferably administered intravenously within 8 hours of the administration of the agent which can cause bone marrow damage. The extremely low dosages particularly preferred in this invention do not cause any significant side effects.

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Newton, MA, United States of America

Therese K Schmalbach