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)

Interferon alfa-2b (Intron A; Schering Plough) has been shown to be active in advanced previously treated multiple myeloma (MM). Recent in vitro evidence has suggested synergy between cytotoxic agents and interferon alfa-2b. This phase I-II protocol was initiated to study interferon alfa-2b in combination with melphalan and prednisone. Groups of five patients received interferon alfa-2b twice-weekly for two weeks at dose levels of 0.5, 1.0, 2.0, 5.0 and 10.0 X 10(6) IU/m2. During week 2, melphalan (9 mg/m2) and prednisone (40 mg/m2) were administered concurrently with interferon alfa-2b followed by a rest period during nadir myelosuppression, the cycles being repeated every 28 days. Thirty patients were entered of whom 21 were Stage III, 3 Stage II and 6 Stage I. Median nadir WBC/mm3 and platelets/mm3 at the various dose levels are given in the table. Serious adverse reactions while on study included myocardial infarction, renal failure and leukopenia-related sepsis. Early response information is available. Twenty-six patients are evaluable for response. Seven have had progressive disease and 19 (69%) a partial response, the median duration was 11+ months. Interferon alfa-2b does not appear to antagonize melphalan/prednisone effectiveness and may be additive or synergistic. Full evaluation of this combination will be undertaken in randomized controlled trials which are now underway.
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PMID:Interferon alfa-2b/melphalan/prednisone in previously untreated patients with multiple myeloma: a phase I-II trial. 359 2

Natural interferon-alpha preparation "Sumiferon" was recently developed in Japan. This is a human lymphoblastoid interferon (HLBI) preparation. Like other interferon preparations, this preparation showed both direct and indirect antitumor effect and the toxicities were moderate. The phase I-II studies were carried out in 38 major institutions in Japan. In the phase I study in 5 patients with advanced breast cancer, the maximum tolerated dose (MTD) was found to be 12 X 10(6) units/day given for 1 month. In the phase II study, HLBI was given in at 3 approximately 6 X 10(6) units/day. Out of 391 cases, 280 were evaluable. Complete and partial responses (CR and PR) were observed in 40 (14.3%) out of 280 evaluable cases, including 11 (19.6%) out of 56 renal cell cancer, 14 (19.2%) out of 73 multiple myeloma, and 9 (17.3) out of 52 malignant lymphoma among others. Major side effects observed were: fever (69.8%), gastrointestinal disturbances (31.4%), leukopenia (30.7%), thrombocytopenia (27.8%), hepatotoxicities (23.6%) and general fatigue (22.1%). Sumiferon seemed to be one of useful antitumor drugs effective against renal cancer.
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PMID:[Introduction of natural interferon-alpha "Sumiferon"]. 363 77

Four weeks after returning from a holiday on Ischia, a 53-year-old man fell ill with nocturnal sweating, fever, severe general malaise and hepatosplenomegaly. Sternal marrow and liver punctures revealed an infection with Leishmania donovani, i.e. Kala-Azar. Characteristic features were hyperplasia of the plasma cells in the bone marrow and liver, together with lymphoplasmocytoid cell wash-out and polyclonal IgG proteinaemia. Treatment with pentamidine (Lomidine) was unsatisfactory, while all manifestations of the disease regressed after two courses of sodium stibogluconate (Pentostam), although the hypergammaglobulinaemia and hyperproteinaemia disappeared only slowly. The plasma-cell hyperplasia in conjunction with the hypergammaglobulinaemia, which suggest multiple myeloma, is interpreted as a result of antibody formation by the chronic parasitic infection. Together with storage-cell hyperplasia it is also taken to be the cause of the peripheral leukopenia and thrombocytopenia.
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PMID:[Kala-azar originating in Ischia]. 365 55

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

Twenty-one patients with alkylator-resistant plasmacell neoplasms were treated with Peptichemio (PTC) at a dose of 40 mg/m2 for 3 days every 3 weeks or, in the case of persistent leukopenia and/or thrombocytopenia, at the single dose of 70 mg/m2 every 2-3 weeks according to haematological recovery. Seventeen patients, 10 with multiple myeloma and seven with extramedullary plasmacytoma (EMP), were fully evaluable. Six of 17 patients (35%) responded: three of seven EMP patients had a complete remission and 3 of 10 multiple myeloma patients had an objective response greater than 50%. The median duration of response was 8.5 months. An EMP patient obtained a complete response lasting for 16 months. The most frequent toxic effect were phlebosclerosis, occurring in all the patients, and myelosuppression, which was severe in only one case. PTC appears to be an active drug in patients with plasmacell neoplasms even if resistant to alkylating agents.
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PMID:Peptichemio in pretreated patients with plasmacell neoplasms. 378 Aug 12

A Phase II study of recombinant leukocyte A interferon (rIFN-alpha A, Ro 22-8181) was performed in 121 patients with hematological malignancies at 33 institutions from July, 1982 to May, 1984. Patients received Ro 22-8181 by intramuscular injection daily for more than 4 weeks. Daily doses were escalated from 3 X 10(6) to 6X, 9X, 18X, 36X and 50X 10(6) units every 3-7 days. Among 70 evaluable cases, complete or partial responses were observed in 15 patients (21.4%). One complete and 10 partial responses (22.4%) were noted in 49 cases of multiple myeloma, 2 partial remissions (18.2%) in 11 cases of malignant lymphoma and 2 partial remissions (25.0%) in 8 cases of leukemia. Side effects included fever (57.0%), anorexia (34.2%), nausea-vomiting (22.8%), malaise (19.0%), leukopenia (44.3%), thrombocytopenia (45.6%) and increase of GOT or GPT (26.6% or 22.8%). They were all not serious and disappeared quickly after the discontinuation of Ro 22-8181.
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PMID:[Phase II study of recombinant leukocyte A interferon (Ro 22-8181) in hematological malignancies]. 388 64

A Phase I study of interferon alfa-2a was conducted in 20 patients with disseminated cancer to establish the relationship between dose and interferon-related side effects. Fever was the most common side effect, and was not dose-related. Other side effects not related to dose included flu-like symptoms, gastrointestinal symptoms, and numbness of fingers and toes. A dose-response relationship was seen for leukopenia, thrombocytopenia, and the elevation of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT). A Phase II study was then conducted in 641 patients to evaluate the efficacy of interferon alfa-2a in a number of disseminated malignant neoplasms. The 415 male and 226 female patients, almost all of whom had malignancies refractory to standard therapy, were treated with interferon alfa-2a at an initial daily dose of 3 X 10(6) U for 3 days. Doses were increased gradually at 3- to 7-day intervals until the therapeutic dosage was established. The daily dose could not exceed 50 X 10(6) U, and treatment was continued for at least one month. Efficacy rates, for 65 patients who achieved partial or complete responses, based on the total number of evaluable patients by cancer type were: 11/49 (22.4%), multiple myeloma; 4/21 (19%), lymphomas; 15/108 (13.8%), renal cell carcinoma; 2/30 (6.6%), bladder cancer; 4/39 (10.2%), brain tumors; 5/26 (19.2%), melanoma; 12/12 (100%), cutaneous lymphoma; 10/19 (52.6%), other skin cancers; 2/30 (6.6%), bone and soft tissue sarcomas. Overall, 65/371 (17.5%) of evaluable subjects responded.
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PMID:Clinical studies of recombinant interferon alfa-2a (Roferon-A) in cancer patients. 394 42

Thirty-five fully evaluable patients with advanced multiple myeloma, refractory to standard chemotherapeutic agents, were entered into a phase II trial with mitoxantrone at a starting dose of 12 mg/m2 iv every 3 weeks. There was one (3%) partial response (lasting 2 1/2 months) in a patient who had received treatment with five different agents, including doxorubicin (total dose, 150 mg/m2). Four additional patients (11%) showed objective evidence of clinical improvement, lasting 4-7 months. Mitoxantrone was well-tolerated with no drug-induced deaths and only moderate to severe leukopenia as the dose-limiting toxicity in the majority of patients. Although mitoxantrone had a low level of activity in this heavily pretreated patient population, consideration should be given to future trials incorporating mitoxantrone into a new drug combination.
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PMID:Phase II trial of mitoxantrone in multiple myeloma: a Southwest Oncology Group Study. 409 95

A disease in mink has been discovered that has many of the features of collagen diseases in man. Affected animals suffer from wasting with leukopenia and thrombocytopenia as well as plasma cell infiltration, hypergammaglobulinemia, glomerulonephritis, arteritis and amyloidosis. Cell-free filtrates and ultracentrifugates from diseased animals induced the disease in normal mink, and aleutian genotypes were unusually susceptible to infection. This genotype was characterized by abnormal lysosomal structures in all the granule-forming cells, resembling the Chediak-Higashi syndrome of man. Anti-gamma-globulin factors similar to human rheumatoid factors were reported, although tests for antibodies such as ANF and LE factors have been negative. Arteritis and glomerulonephritis lesions stained positively for gamma-globulin, and Coombs-type sensitized red cells have been detected in the majority of affected mink. Some mink develop a monodispersion of hypergammaglobulinemia resembling the serum protein changes in human myeloma. These studies highlight genetic, immunological and microbiological causative factors in a mink disorder resembling human collagen disease.
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PMID:Viral plasmacytosis (Aleutian disease) of mink resembling human collagen disease. 533 35

Vincristine 0.25 mg/m2 by IV push and bleomycin 5 units daily by continuous infusion were given on days 1, 2, 3 and 4, together with prednisone 1,000 mg/m2 po in 4 divided doses either on days 1, 3, 5, and 7 (6 patients) or on days 1 and 3 (11 patients) to 17 patients with various lymphoproliferative diseases who had failed their previous treatment program. Fourteen were leukopenic and/or thrombocytopenic. Of 10 patients with non-Hodgkin's lymphoma 2 achieved complete remission and 5 a partial response. Both patients with Hodgkin's disease achieved partial response. A decrease in plasma M protein (median decrease 51%) was observed in 3/3 patients with multiple myeloma and 2/2 with Waldenstrom's macroglobulinemia. Decrease in tumor cell infiltration by 48%, 58% and 100% was observed in 3 patients (2 with macroglobulinemia and 1 with myeloma) in the bone marrow. Leukopenia of less than 3,600/mm3 and thrombocytopenia of less than 70,000/mm3 reverted to normal in 5/7 and 7/10 patients, respectively. Remission duration ranged from 4 to 35+ weeks (median 17 weeks). Three patients had severe GI bleeding. Psychosis controlled by phenothiazines was observed in one, and bleomycin toxicity (anaphylaxis, skin rash, and lung toxicity, one each) was observed in 3 patients. No severe neurotoxicity was observed.
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PMID:Treatment of refractory lymphoproliferative diseases with daily, low-dose vincristine, continuous infusion of bleomycin, and high-dose prednisone. 620 45


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