UMLS:C0026764 - FACTA Search

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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

Patients who have received radiation to localized areas of marrow eventually regenerate marrow in the irradiated area, if the dose is 2,400 centigrays (cGy) or less. This trial was designed to deliver a radiation dose of 1500 cGy to all marrow containing sites in patients with multiple myeloma, a technique we refer to as total bone marrow irradiation, or TBMI. Patients with previously untreated myeloma received 12 weeks of melphalan (L-PAM) and prednisone (pred) therapy. Four weeks later, sequential irradiation was administered using the 3-2 technique with rest periods to permit recovery from radiation-induced cytopenia. This was followed by electron beam irradiation of the rib and skull fields. Following completion of TBMI, patients were untreated until relapse. Twenty patients were entered. At entry 5, 8, and 7 patients had low, intermediate and high tumor cell loads, respectively. Two patients had a serum Ca in excess of 12 mg/dl; 3 had an increased creatinine. The median performance (ECOG) was 1. At week 16, immediately prior to TBMI, 5 of the 20 patients fulfilled the Myeloma Task Force criteria for response and 5 others had improved. Six patients did not begin the radiation therapy portion of the protocol. Three had rapidly progressive disease, one persistent leukopenia, one refused radiation therapy and one was withdrawn by his physician. Only 6 of the fourteen patients receiving the radiation treatment phase of the protocol were able to tolerate the intended course of 1500 cGy to all areas. Eight other patients received lower doses. Patients completing the radiation phase of the protocol failed to have further reductions in M-protein or improvement in other parameters beyond those obtained on the chemotherapy phase of the protocol. The median duration of response and survival was 12.0 and 42 months, respectively. We suggest possible reasons for the disappointing results of this trial and conclude that this approach to the primary treatment of myeloma holds little promise.
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PMID:Melphalan and prednisone plus total bone marrow irradiation as initial treatment for multiple myeloma. 277 82

Six patients with multiple myeloma were treated with HLBI-MP regimen; HLBI 300 X 10(4)U/day daily, Melphalan 4 mg/day p.o. from day 1 to 4 and prednisolone 20 mg/day p.o. from day 1 to 4. Two patients had been refractory to a combination chemotherapy consisting of vincristine, cyclophosphamide, prednisolone and/or adriamycin, while the other 4 patients had been previously untreated. With the HLBI-MP regimen, 3 of 6 patients showed clinical effects. Among the two patients previously treated, one showed an improvement in performance status and the other disappearance of plasmacytoma, respectively. One previously untreated patient showed more than 50% reduction of M-protein. Slight to moderate leukocytopenia was found in all cases, but this was controlled without need for cessation of HLBI. HLBI-MP regimen is thus expected to be useful in the clinical management of patients with multiple myeloma.
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PMID:[Clinical trial of a combination of human lymphoblastoid interferon (HLBI), melphalan and prednisolone (HLBI-MP) in multiple myeloma]. 357 31

The glutathione (GSH) synthesis inhibitor, buthionine sulfoximine (BSO) was tested for cytotoxicity and thiol depletion in murine and human tumor cells in vitro, and for its antitumor activity and toxicity in vivo. The cell lines used in these studies included murine L-1210 leukemia, human RPMI 8226 myeloma, MCF-7 breast cancer and WiDr colon carcinoma. Soft agar colony forming assays showed that BSO was most effective at reducing tumor colony formation when exposed continuously to cells in vitro. Drug concentrations which inhibited colony formation to 50% of control levels ranged from 2.0-6.2 mM (for 1 hour exposures), 2-100 mM for 24 hour exposures and 0.4-1.40 microM (for continuous BSO exposures). Human myeloma cells proved most sensitive to BSO. In vitro cytotoxicity correlated with depletion of intracellular nonprotein sulfhydryls to less than or equal to 10% of control values in both L-1210 and 8226 cells. This was routinely achieved with prolonged exposures to mM BSO concentrations for greater than 24 hours. Normal mice tolerated high BSO doses (up to 5.0 g/kg) without evidence of acute toxicity. BSO was not active against L-1210 leukemia-bearing DBA/2 mice. When tested in vivo against MOPC-315 plasmacytoma-bearing BALB/c mice, BSO was not active at doses up to 4.0 g/kg. In contrast, the bifunctional alkylating agent melphalan (L-PAM) was active against MOPC-315 and this activity was enhanced by a 24 hour pretreatment of mice with 50 mg/kg of L-BSO.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytotoxic effects of glutathione synthesis inhibition by L-buthionine-(SR)-sulfoximine on human and murine tumor cells. 358 42

BALB/c mice cured of a large MOPC-315 or MOPC-104E plasmacytoma following treatment with a low dose (2.5 mg/kg) of melphalan (L-PAM) were resistant to challenge with the other plasmacytoma but to a much lesser extent than to challenge with the autochthonous plasmacytoma. The resistance of the L-PAM-cured MOPC-315-tumor bearers to challenge with MOPC-104E tumor cells was increased when the MOPC-104E tumor cells were admixed with MOPC-315 tumor cells prior to their inoculation. This enhanced resistance to MOPC-104E cells was due to elimination of the MOPC-104E tumor cells through an innocent bystander killing effect since it did not render the mice more resistant to a subsequent challenge with MOPC-104E tumor cells alone. Administration of carrageenan to L-PAM-cured MOPC-315-tumor bearers 1 day after the challenge with the mixture of MOPC-104E and MOPC-315 tumor cells drastically reduced the ability of the mice to resist the tumor challenge. All of the tumors that developed in such mice were of MOPC-104E origin only (as judged by the binding specificity of the myeloma proteins secreted by the tumor cells as well as that present on their surface) even though (a) the tumor inoculum used consisted of up to 10-fold more MOPC-315 than MOPC-104E tumor cells and (b) the MOPC-315 tumor cells divide more rapidly. The same protocol of carrageenan treatment did not reduce the ability of normal BALB/c mice to develop in vivo a primary cell-mediated cytotoxic response nor a primary antibody response indicating that it has no effect on the initiation of an immune response. Therefore, it is conceivable that carrageenan treatment reduced the ability of L-PAM-cured MOPC-315-tumor bearers to reject a challenge with MOPC-315 and MOPC-104E tumor cells by interfering at the effector stage. The ability of the L-PAM-cured MOPC-315-tumor bearers to reject the MOPC-315 cells present in the challenge mixture was reduced when the mice were treated with anti-Thy 1.2 antibody but not with carrageenan, indicating that T-cells independent from carrageenan-sensitive effector cells are required for the rejection of the MOPC-315 tumor cells. Thus, at least two different effector mechanisms participate in the rejection of a challenge composed of MOPC-315 and MOPC-104E tumor cells by L-PAM-cured MOPC-315-tumor bearers.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Some characteristics of the in vivo antitumor immunity exhibited by mice cured of a large MOPC-315 tumor by a low dose of melphalan. 367 24

Pharmacokinetic studies in 11 patients with multiple myeloma were undertaken on the first and last days of one course of chemotherapy. The drug was administered PO in single doses of 6-14 mg daily. Melphalan concentrations were determined by high-performance liquid chromatography. The interpatient variability of pharmacokinetic parameters noted by other authors was observed. Regression analysis showed a significant positive correlation between the elimination rate constant for melphalan and renal function (P = 0.003). The form of the line which describes the overall elimination rate constant for melphalan is given by the equation: Kel = 5.67 X 10(-3) + [4.90 X 10(-5) X GFR]. There was also a significant negative correlation between renal function and the area under the plasma melphalan concentration/time curve (P = 0.006). In vitro stability studies of melphalan in plasma at 37 degrees C and pharmacokinetic data suggest that hydrolysis and renal clearance are the major mechanisms of melphalan elimination. This work shows quantitatively the relationship between renal function and drug elimination and how the data may be used in predicting melphalan half-life from creatinine clearance.
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PMID:Renal function in the elimination of oral melphalan in patients with multiple myeloma. 371

The Authors have described a case of interstitial pneumonia due to 1-phenyl alanine (Melphalan). This case report, where a diagnosis of myeloma of the lung was excluded, was characterised by contact with a single cytotoxic agent in low doses and a short delay before the appearance of the pneumopathy. The different cytotoxic substances capable of inducing such pulmonary lesions are recalled as well as the mechanisms responsible for the phenomenon. The Authors compare their observations to the 5 well documented cases in the literature and suggest that hypersensitivity may have been a contributory factor in their case.
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PMID:[Interstitial pneumopathy caused by melphalan]. 372 61

It is well known that the case of multiple myeloma shows punched-out lesions of the cranium without intracranial hypertension. In this paper a case of multiple myeloma is reported showing intracranial hypertension due to a large tumor that developed in the left parietal bone. There are only 13 case reports about cranial mass lesion of multiple myeloma since 1928. A 52 year-old female was admitted to Iwate Prefectural Isawa Hospital suffering from headache, nausea and vomiting. She had been already diagnosed as multiple myeloma and treated with chemotherapy using Cyclophosphamide, Melphalan and Prednisolone for 2 years. On admission, a large subcutaneous mass was presented on the left parietal region. Craniogram revealed large osteolytic lesion of the left parietal bone and 3 punched-out lesions of the frontal bone. CT scan revealed a large mass lesion in the left epidural space, diploe and subcutaneous space. Angiography showed avascular area. Brain scintigram showed diffuse hot area. Other skeletal bones showed no abnormality. Laboratory examination revealed high concentration of gamma-globulin and high erythrocyte sedimentation rate. Electrophoresis showed high value of immunoglobulin G; immunoglobulin assay was as follows: IgG-6000 mg/dl, IgA-150 mg/dl, IgM-410 mg/dl, IgE-0 mg/dl. Serum electrolytes were within normal limits. Urine didn't include Bence-Jones protein. The patient was diagnosed as multiple myeloma suffering from intracranial hypertension caused by large tumor which developed in the left parietal bone. On the operation, large tumor was existed in the epidural and subcutaneous space invading into the diploe but without infiltration into the dura mater or cerebral cortex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case of multiple myeloma showing intracranial hypertension due to large cranial mass lesions]. 375 28

Recombinant DNA technology has made adequate quantities of human interferons available for both in vitro and in vivo testing. In the clonogenic assay, RPMI-8226 myeloma cells were tested with recombinant interferon alfa-2b (Intron A), melphalan, cyclophosphamide, and prednisone. Prednisone used as a single agent had the least cytotoxic effect. Concentrations of alfa-2b as low as 1 unit/mL (international antiviral activity) showed a reduction in colony number of less than 30% of the untreated controlled cultures. Melphalan and cyclophosphamide showed measurable cytotoxic activity, expressed in terms of 50% inhibition of colony growth, at doses of 0.15 microgram/mL and 0.4 microgram/mL, respectively. Additive antiproliferative effects were noted with combinations of alfa-2b plus cyclophosphamide and alfa-2b plus prednisone. However, the alfa-2b-melphalan combination had a synergistic effect on tumor-cell colony reduction. Even greater cytotoxic activity was seen with the three-drug combination of alfa-2b, melphalan, and prednisone. Clinical trials have shown that alfa-2b may be effective in patients with relapsing and refractory multiple myeloma. Of 38 patients evaluated, seven responded to treatment. Three of the seven responders have continued to respond for over 33 months, with monoclonal proteins approaching undetectable levels. A pilot study of the feasibility of combining alfa-2b with melphalan and prednisone in previously untreated patients with multiple myeloma has been completed. Although response was not the primary objective of this study, an overall response rate of 78% was achieved using criteria established by the Chronic Leukemia Task Force. Phase II trials conducted thus far have established tumor responsiveness to interferons in human myeloma. To clearly define the role of these agents in the treatment of myeloma, well-planned multicenter studies are needed.
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PMID:Interferons in the treatment of multiple myeloma. 376 41

Since interferon alfa-2b (Intron A) is useful as a single agent, it is important to determine if interferon can be combined with standard chemotherapy to improve both response and survival in patients with cancer. Using clonogenic assays, interferon was tested alone and in combination with cyclophosphamide (Cytoxan) or melphalan (Alkeran) using several dose and exposure schedules to evaluate cytotoxicity. In vitro, continuous-exposure interferon produced optimal cell kill. Maximum enhancement of cytotoxicity occurred with cyclophosphamide or melphalan pretreatment (1 hour) and/or simultaneous interferon treatment. Based upon these data, a phase I-II study was designed to determine the tolerance of cancer patients to a fixed dose of cyclophosphamide (150 mg/m2 p.o. daily X 4 days [days 2 to 5]) combined with increasing doses of interferon. Interferon was administered subcutaneously on treatment cycle days 1 to 5, plus days 8, 10, 12, 15, 17, and 19 of the 21-day regimen. Three patients had partial responses: one breast cancer, one angiosarcoma, and one myeloma (mixed). All patients reported mild flu-like symptoms, fatigue, and anorexia. Leukopenia occurred in all patients; three required treatment interruption to allow recovery. Eight patients had a fall in hemoglobin (mean decrease 1.4 g/dL). The combination of cyclophosphamide and interferon was safe and deserves further trial in cancer treatment. However, using this combination schedule, interferon doses greater than or equal to 5 X 10(6) IU were poorly tolerated and compromised administration of full-dose cyclophosphamide.
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PMID:Interferon alfa-2b-cyclophosphamide combination studies: in vitro and phase I-II clinical results. 376 44

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