Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Forty-three patients with disseminated refractory malignancies each received an individually specified combination of either Adriamycin (n = 24) or mitomycin-C (n = 19) conjugated to a cocktail of murine monoclonal antibodies (mAb). Cancers were typed with both immunohistochemistry and flow cytometry using a panel of antibodies. Cocktails of up to six antibodies were selected based on total binding of greater than 80% of the malignant cells in the biopsy specimen. These mAb cocktails were then drug conjugated, safety tested, and administered intravenously. The Adriamycin immunoconjugates were well tolerated in 22/24 patients, with 17/24 having significant side effects. Fever, chills, pruritus, and skin rash were by far the most common transitory reactions. All were well controlled with premedication. A total of up to 1 g Adriamycin and 5 g mAb were administered to each patient. The limiting factor appeared to be a variable dissociation of active Adriamycin from the antibody that unpredictably caused hemopoietic depression. Similar findings were noted among 19 patients treated with mitomycin-C conjugates. Thrombocytopenia at a 60-mg dose of mitomycin-C in this schedule was dose limiting. Serological evidence suggested that the development of an immunoglobulin M antibody specific against the mouse mAb had the specificity and sensitivity to predict clinical reactions. These antibodies were quantitatively less in mitomycin-C-treated patients. Selected patients were retreated. One patient with chronic lymphocytic leukemia was treated on three occasions with regression of peripheral lymph nodes. Two patients with breast carcinoma had definite improvement in ulcerating skin lesions, and two patients with tongue carcinoma had shrinkage of their lesions. No responses were seen with mitomycin-C conjugates but binding was noted to tumors. Drug-induced colitis was seen at higher doses with some binding of these conjugates to normal colon epithelium. This study demonstrated the feasibility of preparing individually specified drug immunoconjugate cocktails for patients with refractory malignancies. Cocktail formulation and antibody delivery to the tumor in vivo was accomplished. There was limited antigenic drift among various biopsies within the same patient over time. The major technical hurdle continues to be the selection of effective drug conjugation methods to optimally bind drugs to mAbs for targeted cancer therapy.
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PMID:Custom-tailored drug immunoconjugates in cancer therapy. 176 66

Forty-three patients with disseminated refractory malignancies each received an individually-specified combination of either Adriamycin (24 patients) or mitomycin-C (19 patients) conjugated murine monoclonal antibodies. Tumors were typed using a panel of antibodies with both immunohistochemistry and flow cytometry. Cocktails of up to six antibodies were selected based on binding greater than 80% of the malignant cells in the biopsy specimen. These monoclonal antibody cocktails were drug conjugated and administered intravenously. Seventeen out of twenty-four patients had reactions to the administration of Adriamycin immunoconjugates, but these were tolerable in all but two patients. Fever, chills, pruritus and skin rash were by far the most common transitory reactions. All were well controlled with premedication. In several patients it was demonstrated that there was limited antigenic drift among various biopsies within the same patient over time. Up to 1 gram of Adriamycin and up to 5 grams of monoclonal antibody were administered. The limiting factor appeared to be a variable dissociation of active Adriamycin from the antibody which unpredictably caused hemopoietic depression. Similar findings were noted in 19 patients with mitomycin-C conjugates. Thrombocytopenia at a 60mg dose of mitomycin-C in this schedule was dose limiting. Preliminary serological evidence suggests that the development of an IgM antibody which is specific against the mouse monoclonal antibody has the specificity and sensitivity to predict clinical reactions. These antibodies were quantitatively less in mitomycin-C patients. Selected patients were re-treated. One patient with chronic lymphocytic leukemia had re-treatment on three occasions and demonstrated regression of peripheral lymph nodes. Two patients with breast carcinoma had definite improvement in ulcerating skin lesions and two patients with tongue carcinoma had shrinkage of their lesions. No responses were seen with mitomycin-C conjugates but binding was noted to tumors and colon with likely drug induced colitis seen after colon binding. This study demonstrates the feasibility and illustrates technical considerations in preparing drug immunoconjugate cocktails for patients with refractory malignancies. Cocktail formulation and antibody delivery was accomplished. The major technical hurdle appears to be the selection of effective conjugation methods that can be used to optimally bind drugs to monoclonal antibodies for targeted cancer therapy.
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PMID:Individually specified drug immunoconjugates in cancer treatment. 250 30

Twenty-three patients with disseminated refractory malignancies each received a tailored combination of adriamycin-conjugated murine monoclonal antibodies. Tumors were typed using a panel of antibodies. Cocktails of up to six antibodies were selected based on binding greater than 80% of the malignant cells as tested by immunoperoxidase and flow cytometry. These monoclonal antibodies were then conjugated to Adriamycin and administered intravenously. Seventeen of 23 patients had reactions to the administration of immunoconjugates, but these were tolerable in all but two patients. Fever, chills, pruritus, and skin rash were by far the most common transitory reactions. All were well controlled with premedication. In several patients there was limited antigenic drift among various biopsies within the same patient over time. This observation confirms the necessity for the use of a cocktail of antibodies if one wishes to cover all tumor cells. Preliminary serologic evidence suggests that the development of an IgM antibody, which is specific against the mouse monoclonal antibody, has the specificity and sensitivity to predict clinical reactions. Selected patients were re-treated. One patient with chronic lymphocytic leukemia had re-treatment on three occasions and demonstrated regression of peripheral lymph nodes. Two patients with breast carcinoma had definite improvement in ulcerating skin lesions and two patients with tongue carcinoma had shrinkage of their lesions. In the course of the study free Adriamycin released from the monoclonal antibodies was discovered to be a limiting factor in the amount of antibody that could be administered. Up to 1 g of Adriamycin and up to 5 g of monoclonal antibody were administered. The limiting factor appeared to be a variable dissociation of active Adriamycin from the antibody that unpredictably caused hemopoietic depression. This study demonstrates the feasibility and reviews technical considerations in preparing immunoconjugate cocktails for patients with refractory malignancies. The major technical hurdle appears to be the selection of an effective conjugation method that can be used to optimally bind Adriamycin to monoclonal antibodies for targeted cancer therapy.
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PMID:Adriamycin custom-tailored immunoconjugates in the treatment of human malignancies. 326 48