Methods for the treatment of malignant disease in patients using citrulline containing amino acid solutions

摘要

Disclosed are total parenteral nutrition formulations which include essential amino acids in combination with either arginine or ornithine, for use in the detection of recurrent malignant disease in patients. Such formulations stimulate tumor-specfic polyamine production to a greater extent than non-tumor related polyamine production. Additionally, such formulations were found to specifically promote an increase in red blood cell putrescine levels of tumor-bearing rats. Nontumor-bearing rats were not found to be similarly reactive to these formulations. Methods for making and administering these formulations as well as their use in preventing DFMO-induced toxicity are also disclosed. Also disclosed are parenteral nutritional formulations which include both citrulline and ornithine which have an arginine concentration of less than about 0.10% by weight final concentration. These formulations inhibit tumor growth and are particularly suited to provide nutritional support for patients with malignant disease. These formulations act to modify the tumor cells ability to compete with normal host tissue for nutrients by modifying the specific content of amino acids administered to the patient. The exact mechanism by which such a formulation alters tumor metabolism is not known, but it has been shown that some of the described formulations result in a reduced rate of tumor cell growth when compared to standard arginine-containign TPN solutions. A method for inhibiting tumor growth and a process for preparing the tumor-inhibiting formulation are also described.