Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Melphalan, ifosfamide, prednisolone, nitrosourea [1-(4-amino-2-methyl-5-pyrimidyl)-3-(2-chloroethyl)-3-nitrosourea hydrochloride, ACNU or 1, 3-bis (2-chloroethyl)-1-nitrosourea, BCNU] and vincristine (MIP-NV) were given in combination to 48 patients with multiple myeloma. The response rate was 57% in previously untreated patients, and 39% in previously treated patients. The median survival time of previously untreated patients in stage IA + IIA was 49 months, and that of patients in stage IIIA + B was 27 months. The median survival time of stage III patients depended significantly on the duration of remission. The duration of remission and survival time of patients with relief of pain and improvement in daily activity were significantly longer than those of patients without such effects. Age, sex, blood hemoglobin concentration and bone lesion were important prognostic factors. As for the side effects, leukopenia (less than 1,000/microliter) and thrombocytopenia (less than 5 X 10(4)/microliter) occurred in 10.4% and 2.1% of the patients, respectively. It was concluded that multiple drug combination therapy with MIP-NV (MIP-NV therapy) was effective for patients with multiple myeloma at all clinical stages, because it resulted in long survival with low toxicity.
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PMID:Combination chemotherapy for multiple myeloma with melphalan, ifosfamide, prednisolone, nitrosourea and vincristine. 316 36

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

A 60-year-old woman was referred to us because of tumors on the occipital and the bilateral submaxillary areas. Biopsy proved them to be well-differentiated lymphosarcoma. On admission, systemic lymphadenopathy was noted and there was 26% of plasmacytoid cells in the bone marrow of the sternum. Monoclonal gammopathy of IgM,K type was found; her disease was diagnosed as a macroglobulinemia (IgM: 8,460 mg/dl). VENP-therapy consisted of vincristine 1 mg/w, cyclophosphamide 50 mg/d procarbazine 50 mg/d and prednisolone 30 mg/d was applied for about four weeks, but in vain. Transaminase levels were elevated (GOT 575 U, GPT 480 U) and the superficial lymphnodes did hardly diminish. Therefore, after improvement of the liver dysfunctions, 5 courses of AAAP-therapy, which was consisted of ACNU 50 mg/d (IV drip over 4 hrs), adriamycin 20 mg/d (IV push), methotrexate 25 mg/d (IV push) and prednisolone 60 mg/d (IV push) once a week or three were employed with excellent clinical effects. The superficial lymphnodes disappeared, M-protein and plasmacytoid cells in the bone marrow markedly decreased. An interval of the initial remission reached to 17 months. As previously reported, AAAP-therapy was also effective to multiple myeloma and acute lymphocytic leukemia of B-cell type. Therefore, AAAP-therapy would be one of the best chemotherapies for B-cell malignancy including macroglobulinemia.
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PMID:[A case report of macroglobulinemia responded to AAAP-therapy]. 682 Sep 7