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)

Thirteen patients with hematological neoplasms were treated with Bestrabucil (100 mg/day po, total dose 700-9,900 mg), which is the benzoate of an estradiol-chlorambucil conjugate. The diseases from which they suffered consisted of T-cell leukemia (3), lymphoma (3), myeloma (5) and essential thrombocytosis (2). Although this drug was less effective against myeloma, the other diseases were more or less relieved with this medication. That is, Bestrabucil was effective in all three patients with T-cell leukemia, both with essential thrombocytosis and two of the three with lymphoma. It is most interesting that adult T-cell leukemia (ATL) cells decreased remarkably with Bestrabucil, along with the disappearance of several symptoms (bone pain, hypercalcemia etc.). The main side effects during this medication were mammary pain (eight of 13 patients, 62%), anorexia (five of 13 patients, 39%) and loss of libido (three of 13 patients, 23%), but neither severe myelosuppression nor hepatorenal dysfunction was induced.
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PMID:[Clinical trial of bestrabucil (KM 2210) in hematopoietic malignancies]. 287 6

A phase 2 trial of vincristine infusion was conducted in a group of 21 patients with refractory multiple myeloma. Patients were generally heavily pretreated with radiotherapy and chemotherapy. Vincristine was given intravenously (IV) as a 0.5 mg bolus and followed immediately by infusion of 0.25 to 0.50 mg/m2/d for 5 days. Courses were repeated every 3 weeks in the absence of disease progression or prohibitive toxicity. Objective responses (partial) were noted in two patients (10%), both of whom were administered 0.5 mg/m2/d infusions. Response durations were brief (2.2 and 1.2 months). Toxicity consisted of neurotoxicity and myelosuppression. In addition to the occurrence of paresthesias and myalgias, ileus (two cases) and moderately severe loss of motor function (two cases) were observed. The mean lowest WBC count following treatment was 2.67 X 10(3)/microL v 3.96 X 10(3)/microL pretreatment (P = .008). The mean lowest platelet count was 75.0 X 10(3)/microL v 106.8 X 10(3)/microL pretreatment (P = .008). Vincristine infusion appears to have limited activity in the treatment of refractory multiple myeloma. Additionally, response durations were short lived and toxicity, both neurologic and hematologic, was appreciable.
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PMID:Single agent vincristine by infusion in refractory multiple myeloma. 299 7

High dose melphalan (HDM, 140 mg/m2 i.v.) has been evaluated in 58 patients under 63 years with multiple myeloma. Among previously untreated patients 11/41 (27%) entered a complete remission (CR: no measurable myeloma protein and a normal bone marrow) and 21 (51%) entered a partial remission (more than 50% reduction in myeloma protein and improvement in all other features). Median duration of remission is 19 months. Two patients who had responded to previous conventional treatment entered CR after HDM. Among 15 patients who had failed on previous chemotherapy the response rate was 66% including two CRs. However, in this group all patients have relapsed within 1 year. Profound myelosuppression, moderate nausea, vomiting, mucositis and diarrhoea with reversible alopecia occurred in all patients. There were 10 deaths within 2 months of treatment mainly due to sepsis and haemorrhage. In a subsequent study, high dose methyl prednisolone (1 g/m2 daily for 5 d) has been added to HDM. Response rates are similar with 6/22 (27%) CR, 13/22 (59%) PR and 2/22 NR but there was only one early death, reflecting improvements in medical management. The high CR rate is an encouraging feature of this approach which is now to be the basis of a prospective trial sponsored by the Medical Research Council in which HDM, with and without steroids, is compared to the best available conventional therapy (the MRC VI Myelomatosis trial).
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PMID:Multiple myeloma treated with high dose intravenous melphalan. 359 57

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

Alpha-2-interferon (IFN) has demonstrable activity in advanced, relapsing, or refractory multiple myeloma. Because of the in vitro synergism between the IFNs and cytotoxic agents, we conducted a trial of 30 previously untreated patients with multiple myeloma utilizing various doses of alpha-2-IFN in combination with standard oral doses of melphalan and prednisone. The combination was well-tolerated without unusual or unexpected toxic effects. The limiting toxicity included dose-related myelosuppression, and alpha-2-IFN induced flu-like symptoms and fatigue. Response was seen in at least as many patients as would be expected with melphalan and prednisone alone. The maximal tolerated dose for a phase II-III trial was 5.0 X 10(6) IU/m2 of alpha-2-IFN in combination with standard doses of melphalan and prednisone. Future trials should utilize this dose of alpha-2-IFN with dose de-escalation according to tolerance.
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PMID:Alpha-2-interferon/melphalan/prednisone in previously untreated patients with multiple myeloma: a phase I-II trial. 369 41

Twenty previously treated patients with multiple myeloma were treated with rDNA human alpha-2 interferon (INTRON A) in a phase II trial. Patients received an induction phase of therapy consisting of 3-100 X 10(6) IU/m2 iv given every other day pending myelosuppression. Patients then received 10 X 10(6) IU/m2 three times a week sc. In patients not responding to the iv and sc protocol, prednisone (20 mg orally) was given with each dose of INTRON A to determine whether additional responses could be produced and whether toxicity could be reduced. During the sc phases of therapy, INTRON A was escalated pending hematologic and nonhematologic toxicity. Three partial remissions were achieved in patients receiving the initial iv/sc therapy, and one additional patient responded when prednisone was added (durations of remission, 5, 6, 8, and 9 months). Myelosuppression was the dose-limiting toxic effect in both the iv and sc phases of therapy. Constitutional symptoms (flu-like) were seen in the majority of patients, but were tolerable. With the utilization of prednisone, flu-like symptoms were reduced in frequency and degree. Escalation of the dose of INTRON A was possible in the majority of patients when prednisone was added; however, only one patient (of seven) responded to combination therapy. INTRON A can produce remissions in 20% of patients with previously treated multiple myeloma. No improvement in the response rate was achieved utilizing a high-dose induction program. Although the dose of INTRON A could be escalated when prednisone was added, the response rate was not enhanced.
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PMID:Phase II study of rDNA alpha-2 interferon (INTRON A) in patients with multiple myeloma utilizing an escalating induction phase. 376 70

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

54 consecutively referred, previously untreated patients with stage II and III multiple myeloma have been treated with the M-2 protocol. 50% of patients had a performance status of less than 50%. 13% were stage II and 87% stage III. In 50 of 54 patients (90%), and objective response according to the Myeloma Task Force was achieved; 10% of the responses have been complete (9+, 15+, 17+, 18+ and 66+ months). Remissions now range from 1 to 86+ months. The actuarial median survival determined from the initiation of therapy will exceed 4 years. Toxicity was acceptable with mild myelosuppression. These results confirm the efficacy of the M-2 protocol in multiple myeloma with regards to response rate and survival.
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PMID:Combination chemotherapy for multiple myeloma with BCNU, cyclophosphamide, vincristine, melphalan, and prednisone (M-2 protocol). 385 63

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

Alpha interferons are biological response modifiers that regulate immune function, slow cell proliferation, and inhibit virus replication. Large supplies of purified preparations are now available for clinical trials. Common toxicity includes an influenza-like syndrome to which tolerance occurs after several doses, and chronic fatigue and anorexia that may be dose-limiting. Myelosuppression is mild. Alpha interferons have established clinical activity against several human cancers, including melanoma, Kaposi's sarcoma, multiple myeloma, non-Hodgkin's lymphoma, hairy cell leukemia, and renal cell carcinoma. These data and alpha interferon nomenclature are summarized in table form. Intranasal alpha interferon is effective in prophylaxis of common viral upper respiratory tract infections, although toxicity in long-term use is prohibitive. Short-term administration to high risk populations may be most useful. Optimal doses and schedules need to be determined for all indications.
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PMID:The new alpha interferons. 391 Mar 84


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