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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Melanoma patients with very advanced disease are usually excluded from chemoimmunotherapy trials; however, the efficacy of intensive treatment regimens needs to be established for this patient population. This study aimed to evaluate the response rate and survival achieved with chemoimmunotherapy in very advanced melanoma patients. Forty-two patients received dacarbazine (250 mg/m2, days 1-3), cisplatin (30mg/m2, days 1-3), interferon-alpha (10 Mio IU/m2 subcutaneously, days 1-5) and intravenous interleukin-2 (18 Mio IU/m2 over 6 h, 12 h then 24 h, followed by 13.5 MioIU/m2 in 72 h). In cases of brain metastases (n = 12) radiation therapy was added. Ten patients (24%) achieved a partial response, 11 (26%) had stable disease and 21 (50%) had disease progression in an intention-to-treat analysis. The median overall survival of patients with a partial response or stable disease was 9 months in contrast to 3.5 months in patients with disease progression. Normal serum lactate dehydrogenase before the start of treatment was a strong favourable prognostic marker for survival (P< 0.002). We conclude that the described treatment schedule offers safe palliation in patients with very advanced metastatic melanoma.
Melanoma Res 1998 Dec
PMID:Long-term outcome of treatment with dacarbazine, cisplatin, interferon-alpha and intravenous high dose interleukin-2 in poor risk melanoma patients. 991 18

Malignant melanoma has a propensity to metastasize widely to many organs, involving the liver in up to one-third of cases. Fulminant hepatic failure is an unusual presentation of hepatic neoplasms, whether primary or metastatic. We describe a case of malignant melanoma with liver metastases that rapidly progressed to fulminant hepatic failure and death. Striking elevations of liver tests, particularly lactate dehydrogenase, were seen. Liver biopsy showed diffuse intrasinusoidal infiltration with melanoma cells. In patients with malignant melanoma, raised serum lactate dehydrogenase levels may suggest hepatic involvement, with extreme elevations possibly predictive of liver failure.
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PMID:Fulminant hepatic failure secondary to malignant melanoma: case report and review of the literature. 993 68

Recent reports on the use of a quantitative measurement of S100B protein for the detection of metastatic melanoma have yielded promising results. In this study we evaluated 489 serum samples from 64 patients suffering from advanced melanoma (UICC/AJCC stage IV) to compare the sensitivity of a S100B immunoradiometric assay (IRMA) with that of conventional blood parameters as well as other known clinical prognostic factors. In a univariate statistical analysis, gender, bone metastasis, and lactate dehydrogenase and S100B levels in serum samples were found to be significant prognostic markers (P<0.05). The S100B level represented the only relevant independent prognostic marker that was sustained in a multivariate analysis (P = 0.016). Furthermore, we were able to demonstrate that S100B is of relevance irrespective of the specific sites of metastatic involvement. The other laboratory parameters could not match the sensitivity rate of S100B. Overall survival rate was strongly associated with serum S100B values. The results of our study suggest that S100B might be a useful tool as a melanoma marker and an independent prognostic factor in advanced metastatic melanoma. S100B serum detection is likely to be of great interest for the pretreatment stratification and/or monitoring of patients enrolled in clinical studies.
Melanoma Res 1999 Apr
PMID:Prognostic significance of serum S100B detection compared with routine blood parameters in advanced metastatic melanoma patients. 1038 Sep 38

In this report, antitumor effects of YoshixolTR in vivo and in vitro were investigated in B16 melanoma cells. For in vivo experiments, the present study shows a dramatic inhibition of tumor growth of B16 melanoma transplanted on the leg or intraperitoneal cavity after treatment with YoshixolTR intraperitoneally. A proliferation of B16 cells in vitro was inhibited by YoshixolTR in a dose-and time-dependent manner. YoshixolTR induced apoptosis-like cell death in histological observations (phase-contrast, scanning and transmission electron microscopy), DNA fragmentation, and a smaller increase in lactate dehydrogenase (LDH) as a marker of cell leakage. Immunohistochemical investigation of cytoskeletal components, such as actin and tubulin, showed a cell wall disruption of B16 melanoma cells and a nuclear extrusion after the treatment with YoshixolTR. Treatment with YoshixolTR in vitro showed an arrest at the G0/G1 stage of the cell cycle, followed by a flow cytometric measurement. As a possible physiological mechanism of YoshixolTR on B16 melanoma cells, intracellular Ca++ was measured with Fura-2 technique. An adequate concentration of YoshixolTR, which induces apoptosis-like cell death, showed a decrease in intracellular free Ca++ concentration. In conclusion, YoshixolTR has an antitumor potency with a new biological mechanism of cell growth, proliferation, and differentiation, including cellular signalling pathways, and is a new candidate for an ideal chemotherapeutic agent against malignant tumors.
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PMID:YoshixolTR inhibits B16 melanoma cell growth in vivo and induces apoptosis-like (quantum thermodynamic) cell death. 1046 54

The biological mechanisms of chemoimmunotherapy efficacy in vivo have not been fully clarified; furthermore, few data are available to predict its efficacy on the basis of clinical and immunological pretreatment factors. In this paper, pre- and post-treatment serum levels of cytokines (interleukin [IL]-6, IL-10, IL-12 and neopterin) and soluble IL-2 receptors (sIL-2R), as well as circulating levels of T-cell and NK subpopulations, were analysed according to clinical outcome in 66 advanced metastatic melanoma (MM) patients treated with subcutaneous IL-2 in association with interferon-alpha, cisplatin and tamoxifen. Our purpose was to correlate the immune modifications during treatment with the clinical response and to define pretreatment factors with predictive value for clinical outcome. The overall response rate was 35%, with a median overall survival of 11.3 months. During treatment, responding patients showed a common marked increase in IL-12 (mainly released by activated macrophages), sIL-2R and neopterin serum levels, associated with high levels of total lymphocytes and circulating natural killer lymphocytes; progressing patients were characterized by an increase in IL-6 serum levels (directly related to the increase in tumour burden). Multivariate analysis showed that high pretreatment IL-12 levels (P = 0.05) and, to a lesser extent, lactate dehydrogenase levels in the normal range (< or = 450 U/I; P = 0.061) are independent favourable prognostic factors for survival. Our results show that macrophage activation in an immunostimulating way either before or during treatment is associated with a better clinical response and improved survival in advanced MM patients treated with IL-2-based chemoimmunotherapy.
Melanoma Res 2000 Feb
PMID:Macrophage-mediated immunostimulation modulates therapeutic efficacy of interleukin-2 based chemoimmunotherapy in advanced metastatic melanoma patients. 1071 41

A phase II study was performed to evaluate the efficacy of cisplatin combined with interleukin-2 and interferon-alpha2b administered subcutaneously to patients with metastatic malignant melanoma (MMM). Between April 1994 and January 1999, 87 patients with MMM and a WHO performance status of < or = 2 were entered into the study. The first 42 patients had prophylactic cimetidine; the other 45 patients did not. An overall response rate of 27% was achieved in the 82 patients evaluable for response. The median response duration was 7.0 months (range 4.4-29.0 months). The median survival for all patients was 10.1 months (range 0.4-64.9+ months). Toxicity was substantial but generally manageable and usually reversed on dose reduction or temporary interruption of treatment. Two patients (2%) died of treatment-related toxicity. No difference in response or survival was seen in the patients treated with or without cimetidine. In multivariate analysis, lactate dehydrogenase level (P < 0.001), number of metastatic sites (P = 0.014) and performance status (P = 0.035) was shown to be independent prognostic factors for survival. This high dose interleukin-2 subcutaneous regimen resulted in a small fraction of long-term survivors. The response and survival results were not superior to other studies using lower and less toxic interleukin-2 doses.
Melanoma Res 2000 Feb
PMID:Subcutaneous interleukin-2 and interferon-alpha plus cisplatin with and without prophylactic cimetidine in patients with metastatic malignant melanoma: a phase II study. 1071 42

Malignant melanoma cells are known to secrete interleukin-6, and elevated interleukin-6 serum levels were reported to correlate with shorter median survival rates. We, therefore, investigated serum values of interleukin-6 and its surrogate C-reactive protein for the ability to discriminate progressive from non-progressive metastatic melanoma disease. Just prior to re-staging examinations, interleukin-6, C-reactive protein and the conventional parameter lactate dehydrogenase were determined in 74 patients with stage IV malignant melanoma according to the criteria of the American Joint Committee on Cancer. We found all tested serum parameters to be significantly elevated in progressive disease. Calculating sensitivities and specificities by logistic regression analysis, the highest sensitivities, according to the established thresholds, were found for interleukin-6 and C-reactive protein with 86% and 76%, respectively. Lactate dehydrogenase had the highest specificity with 94%. Calculating Somers' D rank correlation and the area under the "Receiver Operating Characteristic" curve, all three parameters showed high ability to driscriminate progressive from non-progressive disease. By multiple logistic regression, lactate dehydrogenase was identified to be the most statistically significant marker for progressive disease. We conclude that, comparable to lactate dehydrogenase, interleukin-6 and its surrogate C-reactive protein are useful serum markers for monitoring metastatic malignant melanoma.
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PMID:Interleukin-6 and its surrogate C-reactive protein are useful serum markers for monitoring metastasized malignant melanoma. 1114 23

In metastatic melanoma S100beta as well as melanoma inhibitory activity (MIA) are elevated in the serum in the majority of patients. Elevation has been found to correlate with shorter survival, and changes in these parameters in the serum during therapy were recently reported to predict therapeutic outcome in advanced disease. However, the value of these markers with respect to other possible markers by multivariate analysis has not yet been proven for individual patients. In this prospective study, S100beta and MIA were measured in the serum of 67 consecutive patients before and following treatment. Analysing both the sensitivity and the specificity of the serum parameters by the areas under the receiver operating characteristics (ROC) curves, decreases in S100beta and MIA during therapy were associated with response to therapy, while increases indicated progressive disease. Unexpectedly, the individual diagnostic value of changes in tumour markers during therapy was not superior to one-point measurements at restaging. Moreover, S100beta and MIA were not superior to the conventional parameters lactate dehydrogenase and C-reactive protein (CRP) on multiple logistic regression analysis. Applying classification and regression trees (CARTs), one-point measurements of CRP was shown to be the most relevant overall parameter.
Melanoma Res 2001 Jun
PMID:Are responses to therapy of metastasized malignant melanoma reflected by decreasing serum values of S100beta or melanoma inhibitory activity (MIA)? 1146 18

This analytic (phase II) study aimed to investigate the hypothesis that the decline in serum melanoma-inhibiting activity (MIA) levels following initiation of treatment might have prognostic value. The mean serum lactate dehydrogenase (LDH), MIA and S100 levels in patients with malignant melanoma before treatment were higher than in the control group. Patients with visceral dissemination had much higher mean serum MIA levels than patients with nodal spread only. A regression model was constructed to analyse the prognostic factors in patients with advanced stage malignant melanoma. Therapy included surgical excision or lymph node dissection, hypofractionated radiotherapy, and immunotherapy or chemotherapy. Blood samples were collected within 24 h before the initiation of systemic treatment and two or three times more at 20-28 day intervals. Overall survival was investigated by univariate analysis, and correlation with clinical factors was compared using the log-rank test. Gender, primary tumour site, surgery, radiation therapy, serum S100 levels before systemic treatment and choice of chemotherapy were not correlated with the outcome. In addition to the stage of disease, low serum LDH levels before systemic treatment and a decline in serum MIA levels following initiation of systemic treatment predicted a favourable outcome. Metastasis to visceral organs was associated with higher serum MIA levels. Persistence of high serum MIA levels despite systemic treatment predicts an unfavourable prognosis.
Melanoma Res 2001 Dec
PMID:Prognostic significance of melanoma inhibiting activity levels in malignant melanoma. 1245 54

The purpose of the study was to evaluate serum S100beta protein as a marker of disease activity in patients with malignant melanoma (MM) and compare it with serum alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). One hundred sixty-four patients with MM, stages I-IV according to the American Joint Committee on Cancer (AJCC), were studied. Recurrent disease was categorized as active (AD) if metastases were evident clinically or with imaging investigations and inactive (ID) if no metastases were apparent at the time of sample collection. The sensitivity and specificity of S100beta, LDH, and ALP for discrimination between AD and ID were calculated using receiver-operating characteristic curve (ROC) analysis. Serum S100beta, LDH, and ALP concentrations were significantly higher in AD compared to ID. Serum S100beta protein was the best discriminator between AD and ID, the areas under the ROC curve being 0.89, 0.71, and 0.70 for S100beta, LDH, and ALP, respectively. Serum S100beta and LDH levels (both p < 0.0001) and serum ALP levels (p = 0.0014) corresponded with the number of metastatic sites involved. Using a cutoff point of 0.20 microg/L for serum S100beta protein, a specificity of 93% with a sensitivity of 68% was obtained for AD in MM. In stage IV disease, S100 was an independent predictor of survival in univariate (p = 0.001; hazard ratio = 1.0156) and multivariate (p = 0.038; hazard ratio = 1.0108) analyses. Serum S100beta protein is a better indicator of disease activity in MM than LDH or ALP and is an independent predictor of survival in stage IV disease.
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PMID:Serum S100beta protein as a marker of disease activity in patients with malignant melanoma. 1177 56


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