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)

Prior studies have shown that the P-glycoprotein is a cell membrane efflux pump that is quantitatively increased in expression in multidrug-resistant tumor cell lines. In this study, fresh tumor tissues from patients with multiple myeloma, malignant lymphoma, or metastatic breast cancer were studied immunohistochemically for P-glycoprotein expression and for in vitro sensitivity to doxorubicin. Twenty-six patients who were either previously untreated or in relapse after chemotherapy had tumor specimens submitted that could be evaluated in both assays. The testing was done independently and blindly in separate laboratories instead of our being provided relevant clinical data on the patients. Tumor cells from 12 of the 26 patients (46%) stained positively for P-glycoprotein. Fifteen of the 26 specimens (58%) exhibited drug resistance in vitro. Although only three (21%) of the 14 P-glycoprotein-negative tumors exhibited in vitro resistance to doxorubicin, all 12 fresh tumors that stained positively for P-glycoprotein were resistant to doxorubicin. The difference in frequency of intrinsic doxorubicin resistance between P-glycoprotein-negative and -positive tumors was highly significant (P less than .001). Similar trends were observed in each of the individual tumor categories and were statistically significant in myeloma and breast cancer. Four of the biopsy specimens that stained positively for P-glycoprotein and exhibited doxorubicin resistance were from patients who had not received prior cytotoxic chemotherapy. Similar conclusions were reached when results of drug sensitivity tests were ranked in relation to the median infective dose rather than by criteria based on correlations with clinical drug resistance. Our findings indicate that positive staining for P-glycoprotein associated with multidrug resistance predicts intrinsic cellular resistance of human cancers to doxorubicin. We anticipate that immunohistochemical staining for P-glycoprotein will prove useful in clinical oncology.
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PMID:Prediction of doxorubicin resistance in vitro in myeloma, lymphoma, and breast cancer by P-glycoprotein staining. 256 3

Mitoxantrone is an anthraquinone antineoplastic agent with structural similarities to doxorubicin. It has a mechanism of action similar to the anthracyclines. Its primary elimination route is hepatic metabolism (only seven percent renal excretion) and it has a terminal half-life of approximately 40 hours. Mitoxantrone has significant activity in the treatment of metastatic breast cancer, acute leukemias, and non-Hodgkin's lymphoma. Some activity is reported in head and neck cancer, Hodgkin's, myeloma, bladder cancer, prostate cancer, non-small-cell lung cancer, and liver cancer. There is a suggestion of incomplete cross-resistance between mitoxantrone and the anthracyclines in certain neoplasms. Some activity is reported with mitoxantrone in patients refractory to the anthracyclines in breast cancer, acute leukemias, and non-Hodgkin's lymphomas. The usual doses used in solid tumors and in lymphomas are mitoxantrone 12-14 mg/m2 iv q3-4wk and in leukemias is mitoxantrone 12 mg/m2/d X 5 d iv for initial induction.
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PMID:Mitoxantrone. 351 24

Two women are described in whom, on the basis of prior therapy for breast cancer and the presence of painful, lytic bone lesions, an initial diagnosis of metastatic breast cancer was made. Further evaluation established the diagnosis of multiple myeloma in both patients. Neither had evidence of recurrent breast cancer. These cases indicate that women with a history of breast cancer in whom lytic bone lesions develop without evidence of extraskeletal metastases should have the diagnosis of multiple myeloma excluded.
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PMID:Multiple myeloma masquerading as metastatic breast cancer. 394 26

Fifty-two patients with advanced cancer received sequentially escalating doses of 3 to 50 million units of recombinant DNA-produced alpha interferon by daily intramuscular injection. There were 23 patients with metastatic breast cancer, 17 patients with nodular poorly differentiated lymphocytic lymphoma, and 12 patients with multiple myeloma. Complete and partial remissions were obtained in 35 percent of patients with nodular poorly differentiated lymphoma, whereas rare activity was found in breast cancer and multiple myeloma. Dose-limiting toxicity occurred in patients receiving 36 million units or more and consisted of fatigue/asthenia, weight loss, and elevation of transaminase levels, requiring frequent interruption, reduction in dose, or cessation of treatment. Hematologic toxicity was rarely a limiting factor, but myelosuppression was severe in some patients with multiple myeloma. All toxicities were reversible on discontinuation of treatment. Antibodies to recombinant leukocyte A interferon were seen infrequently but may adversely affect therapy.
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PMID:Collaborative phase I-II study of recombinant DNA-produced leukocyte interferon (clone A) in metastatic breast cancer, malignant lymphoma, and multiple myeloma. 654 79

Paclitaxel is a new anticancer agent with a novel mechanism of action. It promotes polymerisation of tubulin dimers to form microtubules and stabilises microtubules by preventing depolymerisation. In noncomparative trials, continuous infusion of paclitaxel 110 to 300 mg/m2 over 3 to 96 hours every 3 to 4 weeks produced a complete or partial response in 16 to 48% of patients with ovarian cancer and 25 to 61.5% of patients with metastatic breast cancer, many of whom were refractory to treatment with cisplatin or doxorubicin, respectively. 23 to 100% of patients with ovarian cancer achieved complete or partial responses with paclitaxel in combination with cisplatin, carboplatin, cyclophosphamide, altretamine and/or doxorubicin. Similarly, response rates of 30 to 100% were observed with paclitaxel plus doxorubicin, cisplatin, mitoxantrone and/or cyclophosphamide in patients with metastatic breast cancer. Comparative trials in patients with advanced ovarian cancer showed paclitaxel therapy to produce greater response rates than treatment with parenteral hydroxyurea (71 vs 0%) or cyclophosphamide (when both agents were combined with cisplatin) [79 vs 63%]. Paclitaxel was also more effective than mitomycin in 50 patients with previously untreated breast cancer (partial response in 20 vs 4% of patients). Paclitaxel therapy also produced promising results in patients with advanced squamous cell carcinoma of the head and neck, malignant melanoma, advanced non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), germ cell cancer, urothelial cancer, oesophageal cancer, non-Hodgkin's lymphoma or multiple myeloma, and was successfully combined with cisplatin, carboplatin and/or etoposide in patients with NSCLC, SCLC or advanced squamous cell carcinoma of the head and neck. Hypersensitivity reactions were initially a concern with administration of paclitaxel, although current dosage regimens have reduced the incidence of these events to less than 5%. The major dose-limiting adverse effects of paclitaxel are leucopenia (neutropenia) and peripheral neuropathy. Other haematological toxicity was generally mild. Cardiac toxicity was reported in small numbers of patients and most patients developed total alopecia. Several aspects of paclitaxel use remain to be clarified, including the optimal treatment schedule and infusion time, confirmation of the tolerability profile and efficacy of combination regimens in an expanded range of malignancies. Long term follow-up of paclitaxel recipients will also allow the effects of the drug on patient survival to be determined. Nevertheless, paclitaxel is a promising addition to the current therapies available, with significant activity reported in patients with advanced ovarian or breast cancer or other types of tumors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Paclitaxel. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the treatment of cancer. 753 Jun 32

Perhaps the best example of the integration of chemotherapy and biotherapy is autologous stem cell rescue following high dose chemotherapy. This analysis was undertaken to determine the outcome for patients treated in an autologous bone marrow transplant program, which was initiated in January 1989, and to illustrate the impact which biological response modifiers have had on the toxicity, survival, and costs associated with this aggressive treatment approach. Patients with metastatic cancer and good performance status were treated according to disease-specific treatment protocols. Peripheral blood stem cells [PBSC] came into use in 1990, hematopoietic colony stimulating factors [CSFs] in 1991. Outcome was monitored prospectively from the inception of the program. Five years after the program's inception, 75 patients had undergone 96 intensive chemotherapy treatments followed by autologous PBSC rescue. This included 35 patients with breast cancer, 15 with lymphoma or Hodgkin's Disease, five ovary, four melanoma, three sarcoma, three lung cancer, three leukemia, three testicular, two myeloma, one non-lung small cell carcinoma, and one medulloblastoma. Twenty-one patients underwent back-to-back cycles of intensive therapy and rescue; 14 of whom had breast cancer. Twelve patients were treated in 1989, 14 in 1990, 18 in 1991, 14 in 1992, and 17 in 1993. While four of the first 12 patients died within 60 days of reinfusion of cells in 1989, no patients have died within this time frame as a direct result of therapy during the subsequent four years. No patients have been lost to follow-up. Median survival was only eight months in 1989, but has not been reached for subsequent years. For all patients, median failure-free survival (FFS) is 17.2 months; 1-year FFS is 57%, 2-year 36%, and 3-year 29%. Median overall survival (OS) is 30.4 months; 1-year OS 66%, 2-year 52%, and 3-year 42%. From 1990-1993, for patients with metastatic breast cancer (21), and recurrent lymphoma (15), FFS and OS are comparable to the best results published from academic teaching hospitals. Twenty-one patients have survived over two years, 18 of whom continue in remission. Patients were hospitalized for an average of 31 days in 1989, 28.9 in 1990, 24.5 in 1991, and only 13.0-14.0 days in 1992-1993. Two patients were treated entirely as outpatients. Average hospital charges for the 96 treatments have been $120,000 with a range of $15,000 to $461,000, and currently average around $100,000.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The integration of high-dose chemotherapy and biotherapy: initial 5-year experience with autologous bone marrow transplantation in a comprehensive community cancer center. 778 Apr 84

The purpose of this study was to determine the toxicities and potential effectiveness of high-dose busulfan, melphalan and thiotepa (Bu/Mel/TT) followed by autologous peripheral blood stem cell (PBSC) infusion in patients with a variety of diseases. A phase II clinical trial of Bu (12 mg/kg), Mel (100 mg/m2) and TT (500 mg/m2) followed by PBSC infusion in 104 patients with breast cancer (n = 48), malignant lymphoma (n = 25), ovarian cancer (n = 13), multiple myeloma (n = 7) and other malignancies (n = 11) was performed. Sixty-two patients were treated in an academic medical center and 42 in a community cancer center. Grade 3-4 regimen-related toxicities occurred in 14% of patients, causing regimen-related mortality in six (6%) patients with an overall transplant-related mortality of 9%. Transplant-related deaths occurred in 6/62 patients (10%) treated in an academic medical center and in 3/42 (7%) treated in a community cancer center. Complete remissions (CR) were achieved in 1/17 (6%) patients with refractory stage IV breast cancer, 4/4 patients with responsive stage IV breast cancer, 6/13 (46%) with more-advanced lymphoma and 4/4 with less-advanced lymphoma. These patients are alive and disease-free a median of 712, 279, 461 and 404 days after transplant, respectively. Nineteen of 22 patients with stage II-III breast cancer remain alive and disease-free a median of 365 days after transplant. Complete remissions were also seen in 4/9 patients with ovarian cancer and 3/7 with multiple myeloma. The Bu/Mel/TT regimen followed by autologous PBSC infusion is associated with acceptable morbidity and mortality, appears to have significant activity in patients with breast cancer and is well tolerated in the adjuvant setting of stage II-III breast cancer. Bu/Mel/TT also appears to have significant activity in patients with lymphoma, multiple myeloma and possibly ovarian cancer. Further phase II-III studies are warranted in patients with these and other malignancies.
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PMID:Phase II study of high-dose busulfan, melphalan and thiotepa with autologous peripheral blood stem cell support in patients with malignant disease. 880 98

High-dose chemotherapy--in conjunction with the transplantation of either mononuclear cells harvested from the marrow or CD 34+ cells harvested from the peripheral blood--has proved effective in curing certain patients with leukemia, lymphoma, and, to a lesser extent, multiple myeloma. Though the CD 34+ therapy is a relatively new treatment and the mononuclear cell therapy is more standard, both have been successfully used to reconstitute lethally damaged hematopoietic stem cells. Allogeneic transplants have been more effective than autologous transplants against tumors, but they also pose a greater hazard of death from complications, graft-versus-host disease, and infections. More currently, this approach has been used in patients with certain solid tumors, either in a metastatic or recurrent disease setting or as an adjuvant to surgery and/or standard doses of chemotherapy in patients with a known high risk of recurrence. Unfortunately, the majority of the studies about the impact of this therapy have been small and nonrandomized against standard therapy, and they have encompassed diverse populations of patients. This makes comparisons with contemporary standard--dose approaches--already problematic from a statistical point of view--even more dangerous because of the dissimilarity of the groups being compared. Particularly in the high-risk adjuvant setting, data suggest that those patients that meet the eligibility criteria for high-dose therapy and transplantation exhibit the prognostic factors for a positive outcome. When one compares these results with those of a more heterogeneous group of patients treated with conventional therapy, the conclusion might be drawn that high-dose therapy is superior to standard therapy, when a longer follow-up of the patients in the study will show this to be untrue. Thus there is a plea from clinicians and physicians conducting trials for prospective, randomized trials that would allow a fair comparison between high-dose therapy in combination with transplant procedures and a more conventional, standard chemotherapy, which is often less toxic and definitely less expensive. This article reviews the data for transplantation in four tumors: breast cancer, ovarian cancer, small-cell lung cancer, and germ cell testis cancer. There is such a small number of randomized trials that an attempt must be made to compare these small high-dose therapy studies with similar, though not identical, large studies of conventional therapy. This article attempts to make those comparisons, and several conclusions are drawn, which are detailed below. First, few data support the use of high-dose chemotherapy in any patient with recurrent and drug-resistant breast cancer or ovarian cancer. Similarly, few data support the use of high-dose approaches for patients with extensive small-cell lung cancer. For patients with metastatic breast cancer that has responded completely to conventional chemotherapy, no data suggest a survival advantage for the immediate consolidation of that response with high-dose chemotherapy. The only trial addressing this issue found that immediate transplantation led to a better disease-free survival rate, but overall survival, as compared with that of patients who received transplants at relapse, was not affected, and the study did not address the issue of the relative merits of conventional chemotherapy in either case. The only study of high-dose versus conventional chemotherapy was statistically underpowered, and it showed poorer-than-anticipated outcomes in the patients who received conventional therapy. Ongoing or recently completed trials will, it is hoped, address the many unanswered questions in this area. For patients with high-risk, non-metastatic breast cancer, no completed and analyzed phase III randomized studies address the relative merits of conventional versus high-dose therapy. (ABSTRACT TRUNCATED)
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PMID:High-dose chemotherapy and autologous bone marrow or stem cell reconstitution for solid tumors. 965 70

Clinical studies of agents capable of reversing P-glycoprotein (Pgp)-mediated multidrug resistance have attracted much attention in recent years. One question of interest in such studies is whether the concentrations achieved by chemosensitizers are sufficient to inhibit Pgp function. The goal of the present study was to develop a reliable ex vivo bioassay for analysis of the Pgp-inhibiting activity of chemosensitizer-containing patient serum. The fluorescent Pgp substrates daunorubicin (DNR) and rhodamine 123 (R123) were used as probes for Pgp function. The 8226/DOX6 human myeloma cell line, which expresses Pgp at levels that can be detected in clinical cancers, was used as a model system. The index chemosensitizers tested were dexverapamil (DVPM) and cyclosporin A, with particular focus on DVPM. Using flow cytometry, chemosensitizer effects on 1-h drug accumulation and on drug retention at 30 min were evaluated. In the studies using pooled human serum spiked in vitro with graded chemosensitizer concentrations, the order of assay sensitivity was R123 retention >>> R123 accumulation > DNR retention equal to DNR accumulation. Keeping serum spiked with DVPM for several hours at room temperature or 4 degreesC or for several months at -80 degreesC had no effect on Pgp-blocking activity. Sixteen blood samples from patients with metastatic breast cancer receiving DVPM to overcome epirubicin resistance were analyzed for Pgp-inhibiting activity and for levels of DVPM and nor-DVPM, the major metabolite of verapamil. Each patient sample was found capable of increasing R123 retention in the 8226/DOX6 cells, with activity factors of 3- to 8-fold and good agreement between DVPM blood levels and bioassay activity (r = 0.7168; two-sided P = 0.0018). The R123 retention assay developed and validated in this study seems to be a sensitive, reproducible, and easy-to-use method for analysis of Pgp-inhibiting activity of chemosensitizer-containing human serum. The assay seems capable of estimating DVPM blood levels and could prove to be a valuable tool for monitoring chemosensitizer treatment in cancer patients.
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PMID:Sensitive and rapid bioassay for analysis of P-glycoprotein-inhibiting activity of chemosensitizers in patient serum. 981 84

A 72-year-old woman with a history of early breast cancer suffered a fracture of the eighth thoracic vertebra resulting in paraplegia. Magnetic resonance imaging (MRI) showed spinal cord compression by a tumor between the ninth and tenth thoracic vertebrae. Local radiotherapy was begun under the diagnosis of metastatic breast cancer, but bone marrow aspiration and biopsy subsequently revealed plasma-cell proliferation rather than adenocarcinoma. This case report serves to demonstrate that clinicians should consider multiple myeloma as a cause of lytic bone lesions without extraskeletal metastases even in patients with a history of breast cancer.
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PMID:Multiple myeloma mimicking bone metastasis from breast cancer: report of a case. 987 55


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