Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278883 (metastatic melanoma)
 6,224 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.
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PMID:Long-term outcome of treatment with dacarbazine, cisplatin, interferon-alpha and intravenous high dose interleukin-2 in poor risk melanoma patients. 991 18

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.
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PMID:Prognostic significance of serum S100B detection compared with routine blood parameters in advanced metastatic melanoma patients. 1038 Sep 38

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.
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PMID:Macrophage-mediated immunostimulation modulates therapeutic efficacy of interleukin-2 based chemoimmunotherapy in advanced metastatic melanoma patients. 1071 41

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.
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PMID:Are responses to therapy of metastasized malignant melanoma reflected by decreasing serum values of S100beta or melanoma inhibitory activity (MIA)? 1146 18

PURPOSE: To evaluate a panel of pretreatment clinical and laboratory parameters in metastatic melanoma (MM) in order to verify their impact on response and survival in a single prospective multi-institutional phase III study comparing out-patient chemotherapy (CT) vs bioCT. METHODS: A total of 176 patients were randomised to receive CT (cisplatin, dacarbazine, optional carmustine) or bioCT (the same CT followed by subcutaneous IL-2 plus intramuscular alpha-IFN-2b). Pretreatment total leucocytes, lymphocytes, eosinophyls, C-reactive protein (CRP), lactate dehydrogenase (LDH), erytrosedimentation rate (ESR), and fibrinogen were analyzed. Some clinical parameters (performance status, age, sex, and disease site) were also considered. As we found a positive trend for bio-CT with no statistical significance in OR (25.3% vs 20.2%) and OS (11 Mo vs 9.5 Mo), all analyses are stratified by treatment arm. RESULTS: In univariate analysis, higher value of lymphocytes percentage (P <.0001), lower value of total leucocytes (P=.005), CRP (P=.003), LHD (P <.0001), ESR (P <.027), fibrinogen (P <.0001), and no liver disease were strongly related to a better survival. In a multivariate analysis, using the Cox proportional hazards model, only fibrinogen (P=.004), LDH (P=.009) and liver disease (P=.04) were found to have an independent role on clinical outcome in metastatic melanoma patients. CONCLUSION: Liver disease and higher LDH and fibrinogen levels had an important impact on survival in MM patients. In particular, fibrinogen has been recently reconsidered both for its determinant role in the host hemostatic system, and for its capability to provide protection against NK and LAK-cell-induced lysis. These observations could have some important implications for therapeutic approaches, in particular when immunological strategies are used.
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PMID:Fibrinogen: a novel predictor of responsiveness in metastatic melanoma patients treated with bio-chemotherapy: IMI (italian melanoma inter-group) trial. 1469 May 41

The prognosis associated with Stage III melanoma is variable (17-65% 5-year survival) and primarily influenced by the number of lymph nodes involved, the presence of ulceration in a primary lesion, and the tumor burden present in each lymph node. In patients with metastatic (Stage IV) melanoma, the prognosis remains dismal (6-18% 5-year survival) and is influenced primarily by the sites (and extent) of metastatic involvement. Serum lactate dehydrogenase is the only prognostic biomarker useful in metastatic melanoma and it has been incorporated into the 2002 American Joint Committee on Cancer tumor, node, metastasis staging system. In this review, the known prognostic factors in Stage III and IV melanoma are reviewed. Selected investigational therapies and associated biomarkers are also discussed.
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PMID:Biomarkers in melanoma: stage III and IV disease. 1572 93

We aimed to create a prognostic model in metastatic melanoma based on independent prognostic factors in 321 patients receiving interleukin-2 (IL-2)-based immunotherapy with a median follow-up time for patients currently alive of 52 months (range 15-189 months). The patients were treated as part of several phase II protocols and the majority received treatment with intermediate dose subcutaneous IL-2 and interferon-alpha. Neutrophil and monocyte counts, lactate dehydrogenase (LDH), number of metastatic sites, location of metastases and performance status were all statistically significant prognostic factors in univariate analyses. Subsequently, a multivariate Cox's regression analysis identified elevated LDH (P<0.001, hazard ratio 2.8), elevated neutrophil counts (P=0.02, hazard ratio 1.4) and a performance status of 2 (P=0.008, hazard ratio 1.6) as independent prognostic factors for poor survival. An elevated monocyte count could replace an elevated neutrophil count. Patients were assigned to one of three risk groups according to the cumulative risk defined as the sum of simplified risk scores of the three independent prognostic factors. Low-, intermediate- and high-risk patients achieved a median survival of 12.6 months (95% confidence interval (CI), 11.4-13.8), 6.0 months (95% CI, 4.8-7.2) and 3.4 months (95% CI, 1.2-5.6), respectively. The low-risk group encompassed the majority of long-term survivors, whereas the patients in the high-risk group with a very poor prognosis should probably not be offered IL-2-based immunotherapy.
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PMID:Elevated neutrophil and monocyte counts in peripheral blood are associated with poor survival in patients with metastatic melanoma: a prognostic model. 1605 22

This study was conducted to examine the prognostic impact of four biomarkers [tyrosinase and MART-1 messenger RNA (mRNA), S100beta protein and lactate dehydrogenase (LDH)] in patients with metastatic melanoma, together with established clinical factors. Tyrosinase and MART-1 mRNA were measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). S100beta was measured using a commercially available immunoassay, and LDH was analysed conventionally. All markers were measured in blood samples before interleukin-2-based immunotherapy in 85 patients with metastatic melanoma. LDH, S100beta, tyrosinase, number of metastatic sites, location of metastatic sites and performance status were all significant factors for survival in univariate analyses. In multivariate analysis, tyrosinase [hazard ratio (HR)=1.6; 95% confidence interval (CI), 1.1-2.6; P=0.04] and LDH (HR=2.0; 95% CI, 1.1-3.5; P=0.02) were both independent prognostic factors for survival. A combination variable of tyrosinase and LDH remained independently associated with survival (P=0.04) after adjusting for the American Joint Committee on Cancer (AJCC) stage IV classification in a multivariate analysis involving both models. It can be concluded that tyrosinase mRNA and elevated LDH are independent prognostic factors for poor survival in this group of 85 patients. Additional studies are needed before the prognostic value of tyrosinase mRNA in metastatic melanoma can be firmly established. Further evaluation of the combined measurement of tyrosinase mRNA and LDH is warranted.
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PMID:Tyrosinase messenger RNA in peripheral blood is related to poor survival in patients with metastatic melanoma following interleukin-2-based immunotherapy. 1617 68

Serum levels of S100B and/or lactate dehydrogenase (LDH) are putative tumor markers in melanoma. Early changes in such markers may correlate with a positive immune response to vaccine therapy. In patients with metastatic melanoma, S100B and LDH serum levels were measured at baseline, and 1 week after 3 weekly subcutaneous injections of investigational, patient-specific vaccines consisting of autologous dendritic cells loaded with antigens from irradiated proliferating autologous tumor cells, and suspended in granulocyte macrophage colony-stimulating factor. There was a poor correlation between S100B and LDH levels at baseline (p = 0.324). Fourteen (14) patients with measurable disease had higher S100B (p = 0.0456) and LDH (p = 0.0013) levels than 31 patients who lacked measurable disease at that time. Fourteen (14) deceased patients (median survival, 13 months) had a mean baseline S100B of 0.62 mug/L (95% confidence interval [CI] 0.00-1.66) and LDH of 815 U/L (95% CI 222-1408); 31 surviving patients (median follow-up, 35.4 months) had mean S100B of 0.07 mug/L (95% CI 0.00-0.23; p = 0.006) and LDH of 442 U/L (95% CI 296-588; p = 0.002). Elevated baseline levels of LDH and S100B were each predictive of inferior progression-free survival (PFS) and overall survival (OS) (both p < 0.0001), but S100B was a better predictor for PFS than LDH. Changes in LDH between baseline and week 4 were not predictive of survival, but an increase in S100B predicted for inferior OS ( p = 0.039). Both LDH and S100B are predictive tumor markers in patients with metastatic melanoma. This is the first study to examine the changes in serum levels of LDH and S100B in response to an autologous tumor-cell vaccine.
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PMID:Lack of elevation of serum S100B in patients with metastatic melanoma as a predictor of outcome after induction with an autologous vaccine of proliferating tumor cells and dendritic cells. 1845 90


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