Sorafenib and dacarbazine as first-line therapy for advanced melanoma: phase I and open-label phase II studies

Eisen, Tim; Marais, Richard; Affolter, Annette; Lorigan, Paul; Robert, Caroline; Corrie, Pippa; Ottensmeier, Christian; Chevreau, Christine; Chao, David; Nathan, Paul; Jouary, Thomas; Harries, Mark; Négrier, Sylvie; Montegriffo, Elaine; Ahmad, Tanya; Gibbens, I.; James, Maggie; Strauss, Uwe Phillip; Prendergast, Susan; Gore, Martin

doi:10.1038/bjc.2011.257

Cited by 39 publications

(24 citation statements)

References 35 publications

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“…Sorafenib and sunitinib are multi-tyrosine kinase inhibitors that aim to downregulate neoangiogenesis via inhibition of multiple molecular pathways. To our knowledge, there are seven published trials assessing their efficacy in patients with metastatic melanoma (Table 2) [39][40][41][42][43][44][45]. Five out of the seven trials allowed patients with BM to participate.…”

Section: Reviewmentioning

confidence: 99%

Revisiting the role of systemic therapies in patients with metastatic melanoma to the CNS

Papadatos-Pastos

Januszewski

Dalgleish³

2013

Expert Review of Anticancer Therapy

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The CNS is a common site of metastasis in patients with malignant melanoma. Locoregional control either with surgery or radiotherapy is first-line treatment for patients with brain metastasis should they be suitable candidates. For those patients who are not and those who progress after previous treatment, there is an unmet clinical need for effective systemic therapies. Systemic cytotoxics, such as temozolamide and fotemustine, have only modest activity, resulting in a median progression-free survival ranging from 1-2 months, in patients with metastatic melanoma to the brain. Newer systemic treatments such as vemurafenib and ipilimumab have been approved for the treatment of melanoma, but evidence regarding their activity in brain metastases is inconclusive due to the limited access of patients to clinical trials. This is now being revised and more data are emerging supporting the inclusion of patients with brain metastasis in trials. In this review, the authors present data regarding the efficacy of systemically administered therapies in patients with metastatic melanoma to the brain.

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Section: Reviewmentioning

confidence: 99%

Revisiting the role of systemic therapies in patients with metastatic melanoma to the CNS

Papadatos-Pastos

Januszewski

Dalgleish³

2013

Expert Review of Anticancer Therapy

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“…It has been shown that use of sorafenib enhances the response of melanoma to regional chemotherapy (Augustine et al 2010). Anti-cancer activity of sorafenib in malignant melanomas has been demonstrated in several studies (Eisen et al 2011;Escudier et al 2007). Among the latest inhibitors of the aberrant BRAF activity is a synthetic compound PLX4032 (vemurafenib).…”

Section: Braf Gene Mutation V600ementioning

confidence: 99%

Immunohistochemical analysis of the S100A1, S100B, CD44 and Bcl-2 antigens and the rate of cell proliferation assessed by Ki-67 antibody in benign and malignant melanocytic tumours

Sviatoha

Tani

Kleina³

et al. 2010

Melanoma Research

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Malignant melanomas usually have an unfavourable prognosis and poor response to chemotherapy. Deregulation of cell proliferation, programmed cell death and intercellular interactions are among several important mechanisms that might lead to malignant transformation of melanocytes and melanoma progression. The S100A1, S100B, Bcl-2 and CD44 antigens have all been described as being involved in different processes of melanoma progression. The expression of these antigens, as well as the rate of cell proliferation, was analyzed retrospectively in melanocytic tumours from 126 patients (32 males and 94 females, age ranging from 11 to 91 years). The series included benign (45 intradermal, 27 compound and eight displastic naevi) and malignant (39 primary and 14 metastatic) melanocytic tumours. The proliferating rate assessed by Ki-67 staining was lower in naevi than in melanomas, with a correlation coefficient of r = 0814. There was no overlap for rate of proliferation between benign and malignant tumours. The expression of S100A1 was low in benign melanocytic tumours and increased in malignant melanomas (r = 0.61). In contrast, a higher percentage of S100B antigen-positive cells were observed in benign melanocytic lesions than in melanomas (Pearson correlation coefficient, 0.627). In addition, positive immunostaining for S100B antigen in malignant melanomas corresponded with the areas with increased proliferating rate. The expression of Bcl-2 was lower in melanomas than in benign melanocytic tumours (r = -0.53). Bcl-2-negative areas within melanomas had an increased proliferating rate. The expression of CD44 showed a large variation both in benign and malignant melanocytic tumours. CD44 antigen expression was higher in melanomas with known metastases than in those without metastases, but this difference was not statistically significant.

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“…Common genetic mutations Cutaneous BRAF ~ 50% [Davies et al 2002;Cheng et al 2011;Long et al 2011] V600E 80% V600K 16% V600G/R 3% NRAS 20% [Goel et al 2006;Jakob et al 2011] Acral/mucosal c-KIT 10% [Curtin et al 2006;Jiang et al 2008] BRAF/NRAS <10% [Wong et al 2005] Uveal GNAQ ~ 45% [Onken et al 2008;Van Raamsdonk et al 2010] GNA11 ~ 60% [Onken et al 2008;Van Raamsdonk et al 2010] frequent grade 2 and higher adverse events (AEs) associated with vemurafenib were arthralgia (21%), rash (18%), fatigue (13%), alopecia (8%), photosensitivity (12%), nausea (8%) and diarrhoea (5% [Eisen et al 2011;Hauschild et al 2009;McDermott et al 2008]. RAF-265 is another small-molecule multikinase inhibitor of mutant/wild-type BRAF and VEGFR.…”

Section: Melanoma Typementioning

confidence: 99%

Targeted therapy and immunotherapy in advanced melanoma: an evolving paradigm

Khattak¹,

Fisher²,

Turajlic

et al. 2012

Ther Adv Med Oncol

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Metastatic melanoma is one of the most challenging malignancies to treat and often has a poor outcome. Until recently, systemic treatment options were limited, with poor response rates and no survival advantage. However, the treatment of metastatic melanoma has been revolutionized by developments in targeted therapy and immunotherapy; the BRAF inhibitor, vemurafenib, and anticytotoxic T-lymphocyte antigen 4 antibody, ipilimumab, are the first agents to demonstrate a survival benefit. Despite the success of these treatments, most patients eventually progress, and research into response and resistance mechanisms, rationally designed combination therapies and evaluation of the role of these agents in the adjuvant setting is critically important.

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Sorafenib and dacarbazine as first-line therapy for advanced melanoma: phase I and open-label phase II studies

Cited by 39 publications

References 35 publications

Revisiting the role of systemic therapies in patients with metastatic melanoma to the CNS

Revisiting the role of systemic therapies in patients with metastatic melanoma to the CNS

Immunohistochemical analysis of the S100A1, S100B, CD44 and Bcl-2 antigens and the rate of cell proliferation assessed by Ki-67 antibody in benign and malignant melanocytic tumours

Targeted therapy and immunotherapy in advanced melanoma: an evolving paradigm

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