Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper provides an overview of cancer chemotherapy with special reference to the pharmacokinetics of the nitrosoureas. At physiological PH, the chloroethylnitrosoureas can be decomposed into an isocyanate and 2-chloroethyl diazene hydroxide. Therefore, it is clear that they have both alkylation and carbamoylation actions. In addition to the spontaneous chemical dissociation, the nitrosoureas can be metabolized by liver microsomal enzymes to more polar hydroxylated products, and certain nitrosoureas can be denitrosated by these enzymes to the parent urea. Since the lipid-soluble nitrosoureas and some of the water-soluble nitrosoureas such as ACNU and MCNU demonstrated to cross the blood-brain barrier, they have been used in the treatment of primary brain tumors and tumors and tumors of metastatic origin. It has been demonstrated from the results of our study and other reports that the alkylation of DNA by ACNU progresses more slowly as compared with that of other alkylating agents. This is an important finding in relation to the appearance of delayed myelosuppression of the nitrosoureas and in the design of dose schedules of these agents. The major clinical emphasis has been directed towards the more active chloroethylnitrosoureas with reduced myelosuppression, and attempts are now made for this purpose. Unfortunately, the results of phase I and II trials of the newly developed nitrosoureas suggest that these agents produce delayed and cumulative bone marrow toxicity. Antitumor activity of the nitrosoureas is frequestly observed in chronic myelocytic leukemia, malignant lymphoma, brain tumors and small cell carcinoma of the lung, and less frequently in gastrointestinal carcinoma, multiple myeloma and malignant melanoma. In order to enhance clinical effects of the nitrosoureas, further investigation of the design in therapeutic schedules on the basis of their pharmacokinetic characteristics will be needed.
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PMID:[Cancer chemotherapy with special reference to pharmacokinetics of nitrosoureas]. 622 95

The experimental and clinical effects of ACNU so far recorded in Japan are reviewed. ACNU was highly effective in leukemia L-1210 and in other types of leukemias, ascites tumors, and solid tumors of mice and rats. On the basis of the results of phase I study, the maximum clinically tolerable single dose of ACNU was 101.8-135.7 mg/m2 at a time, and the total acceptable dose was 300-600 mg. The desirable interval between doses was 6-8 weeks. Phase II study revealed that ACNU seemed to be effective against small-cell carcinoma of the lung, brain tumors, Hodgkin's disease, and chronic myelocytic leukemia. In the treatment of small-cell carcinoma of the lung ACNU reduced the rate of brain metastasis and prolonged the survival of patients.
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PMID:Experimental and clinical effect of ACNU in Japan with emphasis on small-cell carcinoma of the lung. 624 13

Local chemotherapy by intra-arterial administration of ACNU was performed in 2 cases with CNS leukemia, which responded well to this therapy. The first patient was a 42-year-old male who was diagnosed as having chronic myelogenous leukemia with local infiltration of leukemic cells to the optic nerves. By intra-arterial infusion of ACNU (60mg), symptoms and results of ophthalomological examinations were improved remarkably. The second case was a 16-year-old male diagnosed as having acute lymphoblastic leukemia, and complicating with meningeal involvement during the course of chemotherapy. Complete remission was achieved by intra-thecal administration ACNU. Intra-arterial infusion of ACNU would be an effective local chemotherapy of CNS leukemia and its effectiveness could be achieved by less dose of ACNU compared to that of intravenous infusion. Therefore, side effects, e.g., delayed myelosuppression caused by ACNU could be decreased by this method.
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PMID:[Two cases of central nervous system leukemia which responded excellently to intra-arterial injection of ACNU]. 696 42