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)

Untreated twenty patients of multiple myeloma were treated with the chemotherapy protocol as follows: Initial induction therapy;MP continuous or MP intermittent----IFN alpha----steroid pulse. Maintenance therapy;alkylating agents which have no cross resistance were used ((V) MP----(MP)----(V) EP----MCNU). Remission rate (CR+PR) after the initial MP therapy was 45%, and that after including IFN alpha and steroid pulse therapy was 50%, Fifty percent survival rate was almost as same as those reported previously (34M). Our protocol presented here was based on the idea that, initially, myeloma cells with proliferative activity could be affected by MP therapy, and subsequent IFN alpha therapy would have effect even on the residual myeloma cells. Serial checks of 3H-TdR uptake of myeloma cells during the therapy supported this idea. During the maintenance therapy, clinical responses to the initial induction therapy were not aggravated in the responded cases when evaluated by the variation of serum M-protein level. We propose that considering from a point of proliferative activity of myeloma cells is important for designing therapeutic protocols for multiple myeloma.
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PMID:[Study on the therapy of multiple myelomas--initial induction therapy (MP, IFN alpha, steroid pulse) and maintenance therapy (VMP, MP continuous, VEP, MCNU)]. 163 17

Seventy patients with progressive multiple myeloma received combination chemotherapy with cyclophosphamide and prednisolone (CP), BCNU, cyclophosphamide, procarbazine and prednisolone (BCPP), and MCNU, cyclophosphamide, melphalan and prednisolone (MCMP) as first line treatment. Total remission rate in patients treated with CP, BCPP, and MCMP was 76.2%, 86.1%, and 91%, and complete response rate 26.1%, 33.3% and 63.7%, respectively, 5-yr survival in the patients treated with CP and BCPP regimen was 51.9 +/- 11.1%, 39.7 +/- 8.9%, respectively, however, the difference was not significant, 1-yr survival in the patients treated with MCMP was 91 +/- 8.7%. It was postulated that long-term survival or cure can only be anticipated if the treatments giving high CR rates was developed. The study, though preliminary, supports the notion that MCMP therapy should be used as primary standard treatment for patients with multiple myeloma.
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PMID:[Combination chemotherapy of multiple myeloma]. 238 44

In the clinical phase studies, ranimustine showed very excellent responses against chronic myelogenous leukemia, polycythemia vera and thrombocythemia, and moderate responses against lymphoma or myeloma. The feature of response was the long duration. In cases with CML, CR rate was 82% and maintained for 2-18 months by single administration. In a randomized controlled study, the efficacy of ranimustine was compared with that of busulfan in 77 evaluable previously untreated patients with CML. These included 40 patients for an MCNU group (M) and 37 for busulfan group (B). No difference was seen in the remission rate, crisis rate and survival. A significant difference was observed only in the period of CR. Ranimustine showed almost equal efficacy to that of busulfan but was superior to busulfan in patients who needed rapid responses. The side effects were mild and transient. Despite of its administration by intravenous injection, use of ranimustine seemed convenient, considering the long interval between treatments, being comparable in this respect with oral busulfan. Ranimustine, therefore, seems a very effective drug for myeloproliferative disorders.
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PMID:[Ranimustine]. 240 79

Forty-four patients with progressive symptomatic multiple myeloma were treated with a protocol combining cyclophosphamide (10 mg/kg weekly), procarbazine (2 mg/kg daily), prednisolone (20 mg daily), and either BCNU (1 mg/kg weekly) (BCPP protocol) or MCNU (0.8-1 mg/kg) (MCPP protocol). Of these, 34 patients were treated with the former, and 10 patients with the latter. With BCPP protocol, 12 achieved a complete response, 11 evidenced a 75% response, and 7 displayed a 50% response. With MCPP protocol, on the other hand 2 achieved a complete response, 6 showed a 75% response, and 1 exhibited a 50% response. The median tumor halving time in both groups was 77 days and 57 days respectively. The 5-yr disease-free survival of patients treated with BCPP protocol was 62.0 +/- 10.8%. In MCPP group, 8 of 10 patients are alive with more than 49-87 weeks survival. Although myelotoxicity was moderate, other toxicities were moderate. Toxicity requiring dose modification and discontinuation of the scheduled therapy was observed.
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PMID:[Combination chemotherapy of multiple myeloma--BCNU.cyclophosphamide.procarbazine.prednisolone and MCNU.cyclophosphamide.procarbazine.prednisolone therapy]. 273 69

Sixty-seven patients with hematological malignancies and 4 with cancers were evaluated in this study. Standard administration of MCNU was instituted intravenously using 50-100 mg/m2 every 2 or 4 weeks, whereas some cases were treated with a higher dose therapy. Of 10 patients with chronic myelogenous leukemia, 7 achieved complete remission (CR), and 1 achieved partial remission (PR). A good response was also obtained in 9 of 10 patients with polycythemia vera and in all 4 patients with essential thrombocythemia. MCNU was less effective in malignant lymphoma (ML) and multiple myeloma (MM) than in myeloproliferative disorders. Two of 15 patients with ML and one of 21 patients with MM achieved CR, and two with ML and three MM achieved PR. Three patients with lung cancer and 1 with gastric cancer showed no response to MCNU. Delayed anemia, leukocytopenia and thrombocytopenia were observed in 38.7% of patients, and these were regarded as major side effects of MCNU. Nausea, vomiting, anorexia and elevated transaminase were also found in about 24% of patients, but only transiently. Our study indicates that MCNU is useful for chemotherapy of hematological malignancies, especially of myeloproliferative disorders. Therefore, further studies on combination chemotherapy with MCNU should be developed.
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PMID:[Phase II study of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU)]. 385 48

Forty-two cases of hematological malignancy (18 cases of CML, three cases of polycythemia vera, 10 cases of malignant lymphoma and 11 cases of multiple myeloma) were treated with MCNU. The results obtained were as follows. MCNU was markedly effective on CML cases, being especially useful during the chronic phase, and a partial remission was observed in one of three patients with CML blastic crisis. A good response was observed in all cases with polycythemia vera. In some cases of malignant lymphoma, a fair response was observed. No response was observed in any of the cases of multiple myeloma. Myelosuppression was a major side effect of MCNU, but other side effects other than melena were not severe.
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PMID:[Phase II study with methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU) in hematological malignancies]. 385 50

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 total of 117 cases with hematological malignancies were treated with MCNU at doses of 70-100 mg/m2. Following are the results obtained. 1. MCNU showed a marked depression of cells in the cases with CML, polycythemia vera and thrombocythemia. The low level of cells was maintained for 2 to 7 months. 2. A good response was observed in several cases with blastic crises of CML. 3. No response was observed in two cases with acute leukemia. 4. Although a fair response was observed in several cases with malignant lymphoma or multiple myeloma, moderate bone marrow suppression was observed in a majority of the cases.
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PMID:[Phase II study with methyl-6[[[2-chloroethyl) nitrosoamino] carbonyl] amino]-6-deoxy-alpha-D-glucopyranoside (MCNU) in hematological malignancies]. 634 81

Interferon-alpha (IFN-alpha) is an active therapeutic agent in multiple myeloma. IFN-alpha alone may induce complete or partial responses in approximately 20% of previously untreated patients. However, it remains less effective than conventional chemotherapy. Recently, it proved to be beneficial in some but not all studies, in combination with conventional chemotherapy, to improve the overall response rate and prolong the plateau phase in patients in remission. The Hanshin Hematological Neoplasia Study Group developed a regimen consisting of DMVM (dexamethasone, MCNU, VCR, melphalan) with IFN-alpha. This regimen yields an 69% response rate, including 26% complete remissions defined by disappearance of M-protein and morphological normalization of the bone marrow. The most effective strategy of administration has yet to be established.
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PMID:[The role of interferon-alpha in the treatment of multiple myeloma]. 769 1

A 75-year-old female was diagnosed as having multiple myeloma (IgG.lambda type. Stage IIA) with plasmacytoma of the head and back in October, 1989. She obtained partial remission by MCNU and MP therapy, but relapsed with massive ascites in January, 1991. VAD therapy was not effective and she died of multiple organ failure on February 23. Her ascites contained a large number of myeloma cells, and the phenotypic analysis and the response to interleukin-6 (IL-6) of these myeloma cells were examined. The myeloma cells were positive for CD33, CD45, CD45RA, CD63, CD71, plasma cell associated antigens such as CD38, PCA-1, BL3, and various kinds of adhesion molecules: CD11a/CD18 (LFA-1), CD29 (VLA-beta 1), CD44 (H-CAM), CD49d (VLA-4), CD54 (ICAM-1), CD56 (N-CAM), CD58 (LFA-3). IL-6 level in the ascites was increased at 91.0pg/ml. The myeloma cells showed an IL-6 dependent growth, which was inhibited by anti-IL-6 antibody (Ab) and anti-IL-6 receptor Ab in vitro. Myeloma cells appearing in ascites have rarely been reported. Our case suggested that IL-6 was a potent growth factor of myeloma cells through an autocrine mechanism in the ascites, and resulted in an aggressive myeloma.
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PMID:[Multiple myeloma with massive ascites fluid--immunophenotypic analysis of myeloma cell and its IL-6-dependent growth]. 786 16


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