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)

The aim of the present randomized trial was to compare high-dose therapy (HDT) with continued conventional chemotherapy in patients with multiple myeloma (MM) who responded to the initial treatment. From May 1994 to October 1999, 216 patients (122 men/94 women; stage II or III; Eastern Cooperative Oncology Group [ECOG] score less than 3) entered the study. Initial chemotherapy consisted of 4 cycles of alternating vincristine, BCNU, melphalan, cyclophosphamide, prednisone/vincristine, BCNU, Adriamycin, dexamethasone (VBMCP/VBAD). Responding patients were randomly assigned to receive 8 additional cycles of VBMCP/VBAD, intensification with melphalan 200 mg/m2, or melphalan 140 mg/m2 plus 12 Gy fractionated total body irradiation (TBI). One-hundred sixty-four patients were randomly assigned, 83 to continued chemotherapy and 81 to HDT. The complete remission (CR) rate was significantly higher with HDT (30% vs 11%; P = .002). However, progression-free survival (PFS) was not significantly different between HDT and conventional therapy (median, 42 vs 33 months; P = not significant [NS]), and overall survival (OS) was similar in both groups (median, 61 vs 66 months). Finally, survival after relapse was identical in the 2 arms (15.9 vs 16.4 months). In conclusion, these results show that HDT intensification, when given to myeloma patients who have responded to the initial chemotherapy, significantly increases the CR rate but has no significant impact on PFS or OS.
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PMID:High-dose therapy intensification compared with continued standard chemotherapy in multiple myeloma patients responding to the initial chemotherapy: long-term results from a prospective randomized trial from the Spanish cooperative group PETHEMA. 1610 75

In 2004, multiple myeloma was diagnosed in more than 15,000 people in the United States and will account for approximately 20% of deaths due to hematologic malignancies. Although traditional therapies such as melphalan (Alkeran)/prednisone, combination chemotherapy with VAD (vincristine, doxorubicin [Adriamycin], and dexamethasone), and high-dose chemotherapy with stem cell transplantation have shown some success, median survival remains between 3 to 5 years. Treatment options for patients with multiple myeloma have increased in recent years, with the promise of improvement in survival. New agents, such as the proteasome inhibitor bortezomib (Velcade), the antiangiogenic and immunomodulator thalidomide (Thalomid) and its analogs, such as lenalidomide (Revlimid), together with other small molecules, including arsenic trioxide (Trisenox), and other targeted therapies, have been studied alone and in combination with other antineoplastic therapies, either as induction therapy prior to stem cell transplantation or in patients with relapsed disease. Bortezomib recently was approved in the United States for the treatment of multiple myeloma in patients who have received at least one prior therapy. The use of bortezomib-based regimens as front-line therapy as well as the use of other agents in multiple myeloma remain under investigation, and approvals for both thalidomide and lenalidomide are hoped for soon, with the overall prospect of patient outcome continuing to be increasingly positive.
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PMID:New treatments for multiple myeloma. 1650 32

Not all patients who fulfill the minimal criteria for diagnosis of multiple myeloma should be treated. If doubt exists about beginning therapy, one should wait and re-evaluate the patient in 2 or 3 months. There is no evidence that early treatment of multiple myeloma is advantageous. All patients should be considered possible candidates for an autologous stem cell transplantation. If they are deemed to be eligible, they should be treated for 3 to 4 months with therapy that does not damage the hematopoietic stem cells. Currently, most physicians use thalidomide plus dexamethasone or dexamethasone alone for induction. Vincristine, doxorubicin (Adriamycin), and dexamethasone (VAD) have been used in the past. Autologous stem cell transplantation prolongs disease-free survival and overall survival. The treatment-related mortality rate is 1% to 2%. Melphalan, 200 mg/m2, is the most widely used preparative regimen. Although allogeneic transplantation is attractive, the mortality rate (about 20%) is too high to recommend conventional allogeneic transplantation. Non-myeloablative transplantation is currently under investigation. If the patient is not a candidate for autologous stem cell transplantation, therapy with melphalan and prednisone is a good choice. Patients with relapsed or refractory disease may be treated with dexamethasone, thalidomide and dexamethasone, bortezomib (Velcade, PS-341), or lenalidomide (Revlimid, not yet approved by the Food and Drug Administration).
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PMID:Treatment of multiple myeloma: an emphasis on new developments. 1658 96

The natural history of multiple myeloma (MM) was revolutionized by the introduction of haematopoietic stem cell transplantation to the treatment armamentarium of this disease. Defined subgroups of MM patients (such as the elderly or dialysis-dependent) have required an individualized approach in order to minimize the transplant-related mortality. Little, however, is known about the management of 12-30% of MM patients with coexistent AL amyloidosis as the amyloidopathy is often overlooked and when recognized these patients commonly are excluded from clinical trials. While occult amyloidosis appears to have no impact on the toxicity and outcome of MM patients, the presence of symptomatic amyloidopathy clearly worsens their prognosis. Use of induction chemotherapy drugs that can cause further damage to the heart (Adriamycin), nervous system (Vincristine) or kidneys should be avoided as should lengthy delays in proceeding to autograft. Further, refining the transplant eligibility criteria for this subgroup of patients with co-existent amyloidopathy to include the number of organs involved and the degree of cardiac involvement (NYHA class, Troponins and NT-pro-BNP levels) along with melphalan dose-adjustment will minimize the treatment-related toxicity and mortality and possibly allow a reversal of the organ damage induced by the amyloidogenic light chain.
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PMID:Multiple myeloma-associated AL amyloidosis: is a distinctive therapeutic approach warranted? 1671 10

Pegylated liposomal doxorubicin (Doxil, Caelyx) is associated with less frequent neutropenia, alopecia and cardiotoxicity than conventional doxorubicin and has an improved pharmacokinetic profile, allowing for intravenous administration over 1 hour. In the US and EU (as well as a number of other countries), pegylated liposomal doxorubicin is approved for use in combination with the proteasome inhibitor bortezomib for the treatment of patients with relapsed or refractory multiple myeloma. Results of the primary efficacy analysis of a large phase III trial in bortezomib-naive patients with relapsed or refractory multiple myeloma demonstrated that the combination of pegylated liposomal doxorubicin plus bortezomib significantly prolonged the time to progression (TTP) compared with bortezomib alone. In addition, pegylated liposomal doxorubicin plus bortezomib significantly increased TTP in most subgroup analyses, including in patients with or without previous anthracycline exposure. A number of secondary outcomes, including progression-free survival and overall survival at 15 months, were also improved with the combination compared with bortezomib alone in the overall study population. Pegylated liposomal doxorubicin plus bortezomib was associated with a higher incidence of grade 3 or 4 adverse events than bortezomib alone, which was mainly attributed to an increase in myelosuppression and gastrointestinal events with the combination. These events were predictable and often managed by dosage modifications and supportive therapy. The addition of pegylated liposomal doxorubicin to bortezomib treatment did not increase the incidence of cardiotoxicity or peripheral neuropathy, but did induce hand-foot syndrome in a proportion of patients. Pegylated liposomal doxorubicin plus bortezomib is now established as an additional standard of care in the treatment of patients with relapsed or refractory multiple myeloma who have received at least one prior therapy.
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PMID:Pegylated liposomal Doxorubicin: a review of its use in the treatment of relapsed or refractory multiple myeloma. 1901 77

This study describes a spectrum of renal diseases that can precede the diagnosis of multiple myeloma (MM). Patients presenting manifestations of renal disease were recorded as individual patients of MM. Fifty patients (male 41; female 9) were included in this study. Diagnosis of MM was confirmed by two or more of the following four features: lytic bone lesions, serum or urine monoclonal peak, Bence Jones proteinuria, and greater than 20% plasma cells in bone marrow. Renal disease was present in 42 of 50 (84%) patients before MM was diagnosed. In only eight of 50 (16%) patients, diagnosis of MM preceded the detection of renal disease. Renal diseases consisted of acute renal failure in 26 patients (52%), chronic renal failure in 15 patients (30%) and nephrotic syndrome in 9 patients (18%). Some of the patients with acute or chronic renal failure also had heavy proteinuria. Percutaneous renal biopsy was done in 17 patients. Renal histopathology showed amyloidosis (n = 10), cast nephropathy (n = 5), nodular glomerulosclerosis (n = 1), and mesangioproliferative glomerulonephritis with plasma cell infiltration (n = 1). Hypercalcemia (calcium 11-13.8 mg/dL) was the most common precipitating factor for acute renal failure. All 50 patients received combination chemotherapy of melphalan and prednisolone or vincristine, Adriamycin, and dexamethasone. More than half of the total number of patients did not complete chemotherapy because of death or lost to follow-up. Nineteen patients with acute renal failure and eight patients with chronic renal failure were treated with hemodialysis. Fourteen patients (28%) with acute renal failure had recovery of renal function. Twenty-three patients (46%) were lost to follow-up. Seven patients (14%) died from sepsis, uremia, or hyperkalemia. Remission of MM was found in 9 of 21 (42.8%) patients who completed chemotherapy. Thus, acute renal failure is the most common renal disease preceding the diagnosis of MM. Reversal of renal function is achieved with chemotherapy and hemodialysis treatment.
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PMID:Renal disease is a prodrome of multiple myeloma: an analysis of 50 patients from eastern India. 1946 74

Doxorubicin and pegylated liposomal doxorubicin are key compounds of several induction regimens used prior to autologous stem cell transplantation in patients with de novo multiple myeloma, such as vincristine, doxorubicin, dexamethasone (VAD), vincristine, pegylated liposomal doxorubicin/Doxil, dexamethasone (DVd) or PS-341/bortezomib, doxorubicin, dexamethasone (PAD). The aim of this article is to summarize the more recent data available on the efficacy of these combinations and to discuss their role as part of initial therapy.
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PMID:Combination regimens using doxorubicin and pegylated liposomal doxorubicin prior to autologous transplantation in multiple myeloma. 1958 27

A total of eighty patients with various malignancies seen between September 2008 and April 2009 at the University of Nigeria Teaching Hospital (UNTH) Ituku Ozalla, Enugu, Nigeria, had their absolute neutrophil counts, done at Days 0 and 12 of the first cycle of their various chemotherapeutic regimens. They were adult patients who had been diagnosed of various malignancies, consisting of Breast cancer 36 (45%), Non-Hodgkin's lymphoma 8 (10%), Hodgkin's lymphoma 13 (16.25%), Colorectal carcinoma 6 (7.5%), Multiple myeloma 7 (8.75%), Cervical carcinoma 1 (1.25%) and other malignancies 9 (11.25%), Manual counting of absolute neutrophil count was done using Turks solution and improved Neubauer counting chamber and Galen 2000 Olympus microscope. The socio demographic data of the patients were assessed from a questionnaire. There were 27 males (33.75%) and 53 females (66.25%). Their ages ranged from 18 - 80 years with a median of 45 years. The mean absolute neutrophil count of the respondents pre-and post chemotherapy was 3.7 +/- 2.1 x 10(9)/L and 2.5 +/- 1.6 x 10(9)/L respectively. There were significant differences in both the absolute neutrophil count (p=0.00) compared to the pre-chemotherapy values. Chemotherapeutic combinations containing cyclophosphamide and Adriamycin were observed to cause significant reduction in absolute neutrophil.
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PMID:Absolute neutrophil values in malignant patients on cytotoxic chemotherapy. 2197 Feb 73

This clinical vignette illustrates how our therapeutic approaches to early stages of multiple myeloma have changed over the past decade with novel therapies reducing disease and preventing disease progression. Recent paradigms of multiple myeloma describe the disease as a spectrum of clinical stages, including asymptomatic 'smoldering' states that progress to symptomatic states. The average 5-year survival rate of patients with multiple myeloma diagnosed between 1996 and 2004 according to surveillance epidemiology and end results (SEER) data is 35.9%. Here, we describe the use of novel therapeutic agents including bortezomib, lenalidomide, bisphosphonates, Doxil/Caelyx, and dexamethasone, and their success in affecting the course of disease. Multiple trials have shown an increased benefit of these newer agents over prior multiple myeloma treatment regimens. At 13 years and 8 months from diagnosis, our patient is doing well, and thus is a model of how long-term control of multiple myeloma prolongs survival.
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PMID:Novel therapies delay the progression of smoldering multiple myeloma: Case report and discussion. 2227 34

Doxil, also known as Caelyx, is an established liposomal formulation of doxorubicin used for the treatment of ovarian cancer, sarcoma and multiple myeloma. While showing reduced doxorubicin related toxicity, Doxil does not greatly improve clinical outcome. To become biologically active, doxorubicin needs to be released from its carrier. Uptake and breakdown of the liposomal carrier and subsequent doxorubicin release is not fully understood and in this study we explored the hypothesis that Doxil is taken up by tumor cells and slowly degraded intracellularly. We investigated the kinetics of liposomal doxorubicin (Doxil) in vitro as well as in vivo by measuring cytotoxic effect, intracellular bioavailability and fate of the carrier and its content. To prevent fixation artifacts we applied live cell imaging in vitro and intravital microscopy in vivo. Within 8h after administration of free doxorubicin, 26% of the drug translocated to the nucleus and when reaching a specific concentration killed the cell. Unlike free doxorubicin, only 0.4% of the doxorubicin added as liposomal formulation entered the nucleus. Looking at the kinetics, we observed a build-up of nuclear doxorubicin within minutes of adding free doxorubicin. This was in contrast to Doxil showing slow translocation of doxorubicin to the nucleus and apparent accumulation in the cytoplasm. Observations made with time-lapse live cell imaging as well as in vivo intravital microscopy revealed the liposomal carrier colocalizing with doxorubicin in the cytoplasm. We also demonstrated the sequestering of liposomal doxorubicin in the lysosomal compartment resulting in limited delivery to the nucleus. This entrapment makes the bioavailable concentration of Doxil-delivered doxorubicin significantly lower and therefore ineffective as compared to free doxorubicin in killing tumor cells.
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PMID:Intact Doxil is taken up intracellularly and released doxorubicin sequesters in the lysosome: evaluated by in vitro/in vivo live cell imaging. 2401 86


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