Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Melanoma: HELP
Articles by Dr. Axel Hauschild
Based on 160 articles published since 2008
||||

Between 2008 and 2019, A. Hauschild wrote the following 160 articles about Melanoma.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7
1 Guideline S3-guideline "diagnosis, therapy and follow-up of melanoma" -- short version. 2013

Pflugfelder, Annette / Kochs, Corinna / Blum, Andreas / Capellaro, Marcus / Czeschik, Christina / Dettenborn, Therese / Dill, Dorothee / Dippel, Edgar / Eigentler, Thomas / Feyer, Petra / Follmann, Markus / Frerich, Bernhard / Ganten, Maria-Katharina / Gärtner, Jan / Gutzmer, Ralf / Hassel, Jessica / Hauschild, Axel / Hohenberger, Peter / Hübner, Jutta / Kaatz, Martin / Kleeberg, Ulrich R / Kölbl, Oliver / Kortmann, Rolf-Dieter / Krause-Bergmann, Albrecht / Kurschat, Peter / Leiter, Ulrike / Link, Hartmut / Loquai, Carmen / Löser, Christoph / Mackensen, Andreas / Meier, Friedegund / Mohr, Peter / Möhrle, Matthias / Nashan, Dorothee / Reske, Sven / Rose, Christian / Sander, Christian / Satzger, Imke / Schiller, Meinhard / Schlemmer, Heinz-Peter / Strittmatter, Gerhard / Sunderkötter, Cord / Swoboda, Lothar / Trefzer, Uwe / Voltz, Raymond / Vordermark, Dirk / Weichenthal, Michael / Werner, Andreas / Wesselmann, Simone / Weyergraf, Ansgar J / Wick, Wolfgang / Garbe, Claus / Schadendorf, Dirk / Anonymous5740759. ·Department of Dermatology, University Hospital Tübingen, Germany. ·J Dtsch Dermatol Ges · Pubmed #23721604.

ABSTRACT: -- No abstract --

2 Guideline Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. 2012

Dummer, R / Hauschild, A / Guggenheim, M / Keilholz, U / Pentheroudakis, G / Anonymous3630737. ·Dermatologische Klinik, UniversitätsSpital Zürich, CH-8091 Zürich, Switzerland. ·Ann Oncol · Pubmed #22997461.

ABSTRACT: -- No abstract --

3 Guideline Diagnosis and treatment of melanoma. European consensus-based interdisciplinary guideline--Update 2012. 2012

Garbe, Claus / Peris, Ketty / Hauschild, Axel / Saiag, Philippe / Middleton, Mark / Spatz, Alan / Grob, Jean-Jacques / Malvehy, Josep / Newton-Bishop, Julia / Stratigos, Alexander / Pehamberger, Hubert / Eggermont, Alexander M / Anonymous220737 / Anonymous230737 / Anonymous240737. ·University Department of Dermatology, Tuebingen, Germany. claus.garbe@med.uni-tuebingen.de ·Eur J Cancer · Pubmed #22981501.

ABSTRACT: Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumour and causes 90% of skin cancer mortality. A unique collaboration of multi-disciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on CM diagnosis and treatment, based on systematic literature reviews and the experts' experience. Diagnosis is made clinically and staging is based upon the AJCC system. CMs are excised with one to two centimetre safety margins. Sentinel lymph node dissection (SLND) is routinely offered as a staging procedure in patients with tumours more than 1mm in thickness, although there is as yet no clear survival benefit for this approach. Interferon-α treatment may be offered to patients with stage II and III melanoma as an adjuvant therapy, as this treatment increases at least the disease-free survival (DFS) and less clear the overall survival (OS) time. The treatment is however associated with significant toxicity. In distant metastasis, all options of surgical therapy have to be considered thoroughly. In the absence of surgical options, systemic treatment is indicated. BRAF inhibitors like vemurafenib for BRAF mutated patients as well as the CTLA-4 antibody ipilimumab offer new therapeutic opportunities apart from conventional chemotherapy. Therapeutic decisions in stage IV patients should be primarily made by an interdisciplinary oncology team ('tumour board').

4 Guideline Melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. 2010

Dummer, R / Hauschild, A / Guggenheim, M / Jost, L / Pentheroudakis, G / Anonymous3110663. ·Department of Dermatology, Zürich University Hospital, Switzerland. ·Ann Oncol · Pubmed #20555080.

ABSTRACT: -- No abstract --

5 Guideline Diagnosis and treatment of melanoma: European consensus-based interdisciplinary guideline. 2010

Garbe, Claus / Peris, Ketty / Hauschild, Axel / Saiag, Philippe / Middleton, Mark / Spatz, Alain / Grob, Jean-Jacques / Malvehy, Josep / Newton-Bishop, Julia / Stratigos, Alexander / Pehamberger, Hubert / Eggermont, Alexander. ·Center for Dermatooncology, Department of Dermatology, 72076 Tübingen, Germany. claus.garbe@med.uni-tuebingen.de ·Eur J Cancer · Pubmed #19959353.

ABSTRACT: Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumour and causes 90% of skin cancer mortality. A unique collaboration of multi-disciplinary experts from the European Dermatology Forum, the European Association of Dermato-Oncology and the European Organization of Research and Treatment of Cancer was formed to make recommendations on CM diagnosis and treatment, based on systematic literature reviews and the experts' experience. Diagnosis is made clinically and staging is based upon the AJCC system. CMs are excised with one to two centimetre safety margins. Sentinel lymph node dissection is routinely offered as a staging procedure in patients with tumours more than 1mm in thickness, although there is as yet no resultant survival benefit. Interferon-alpha treatment can be offered to patients with more than 1.5mm in thickness and stage II to III melanoma as an adjuvant therapy, as this treatment increases the relapse-free survival. The lack of a clear survival benefit and the presence of toxicity however limit its use in practice. In distant metastasis, all options of surgical therapy have to be considered thoroughly. In the absence of surgical options, systemic medical treatment is indicated, but with, to date, low response rates. Therapeutic decisions should be made by the melanoma team and the informed patient after full discussion of the options.

6 Guideline Cutaneous malignant melanoma: ESMO clinical recommendations for diagnosis, treatment and follow-up. 2008

Dummer, R / Hauschild, A / Jost, L / Anonymous3710598. ·Department of Dermatology, University of Kiel, Kiel, Germany. ·Ann Oncol · Pubmed #18456782.

ABSTRACT: -- No abstract --

7 Guideline Evidence-based and interdisciplinary consensus-based German guidelines: systemic medical treatment of melanoma in the adjuvant and palliative setting. 2008

Garbe, Claus / Hauschild, Axel / Volkenandt, Matthias / Schadendorf, Dirk / Stolz, Wilhelm / Reinhold, Uwe / Kortmann, Rolf-Dieter / Kettelhack, Christoph / Frerich, Bernhard / Keilholz, Ulrich / Dummer, Reinhard / Sebastian, Günther / Tilgen, Wolfgang / Schuler, Gerold / Mackensen, Andreas / Kaufmann, Roland. ·University Department of Dermatology, Tübingen, Germany. claus.garbe@med.uni-tuebingen.de ·Melanoma Res · Pubmed #18337653.

ABSTRACT: Systemic medical treatment of melanoma is administered in the adjuvant and palliative setting. Adjuvant therapy may be considered in patients with primary melanoma with more than 1.5 mm tumor thickness and with regional node metastasis. Presently no indication for systemic adjuvant chemotherapy or for adjuvant therapy with nonspecific immune-stimulatory agents outside controlled studies is seen. Interferon-alpha is the first substance in the adjuvant therapy of melanoma, which has shown to present a significant advantage to the patients in some prospective randomized studies. Good arguments for using adjuvant interferon-alpha therapy in high-risk melanoma patients exist. Both high-dose and low-dose interferon-alpha show promise. The major indications for systemic chemotherapy and chemoimmunotherapy are inoperable recurrent tumors, inoperable regional metastases and distant metastases (stage IV). As treatment in such situations is primarily palliative, the effect of any regimen on the quality of life must be carefully weighed. As a first line treatment, single agent therapy is recommended, as polychemotherapy or biochemotherapy did not show significant advantages for prolongation of survival; hence they are more toxic. An urgent need for development of new treatment modalities is necessary and general principles of experimental immunotherapy are outlined.

8 Guideline Evidence and interdisciplinary consensus-based German guidelines: surgical treatment and radiotherapy of melanoma. 2008

Garbe, Claus / Hauschild, Axel / Volkenandt, Matthias / Schadendorf, Dirk / Stolz, Wilhelm / Reinhold, Uwe / Kortmann, Rolf-Dieter / Kettelhack, Christoph / Frerich, Bernhard / Keilholz, Ulrich / Dummer, Reinhard / Sebastian, Günther / Tilgen, Wolfgang / Schuler, Gerold / Mackensen, Andreas / Kaufmann, Roland. ·University Department of Dermatology, Tübingen, Germany. claus.garbe@med.uni-tuebingen.de ·Melanoma Res · Pubmed #18227710.

ABSTRACT: The primary treatment of a melanoma is surgical excision. An excisional biopsy is preferred, and safety margins of 1 cm for tumor thickness up to 2 mm and 2 cm for higher tumor thickness should be applied either at primary excision or in a two-step procedure. When dealing with facial, acral or anogenital melanomas, micrographic control of the surgical margins may be preferable to allow reduced safety margins and conservation of tissue. The sentinel lymph node biopsy should be performed in patients whose primary melanoma is thicker than 1.0 mm and this operation should be performed in centers where both the operative and nuclear medicine teams are experienced. In clinically identified lymph node metastases, radical lymph node dissection is considered standard therapy. If distant metastases involve just one internal organ and operative removal is feasible, then surgery should be seen as therapy of choice. Radiation therapy for the primary treatment of melanoma is indicated only in those cases in which surgery is impossible or not reasonable. In regional lymph nodes, radiation therapy is usually recommended when excision is not complete (R1 resection) or if the nodes are inoperable. In distant metastases, radiation therapy is particularly indicated in bone metastases, brain metastases and soft tissue metastases.

9 Review Melanoma. 2018

Schadendorf, Dirk / van Akkooi, Alexander C J / Berking, Carola / Griewank, Klaus G / Gutzmer, Ralf / Hauschild, Axel / Stang, Andreas / Roesch, Alexander / Ugurel, Selma. ·Department of Dermatology, University Hospital Essen, Essen, Germany; German Cancer Consortium, Heidelberg, Germany. Electronic address: dirk.schadendorf@uk-essen.de. · Department of Surgical Oncology, Netherlands Cancer Institute Antoni van Leeuwenhoek, Amsterdam, Netherlands. · Department of Dermatology and Allergy, University Hospital Munich, Munich, Germany. · Department of Dermatology, University Hospital Essen, Essen, Germany; German Cancer Consortium, Heidelberg, Germany. · Department of Dermatology, Hannover Medical School, Skin Cancer Centre Hannover, Hannover, Germany. · Department of Dermatology, University Hospital, Kiel, Germany. · Centre of Clinical Epidemiology, Institute of Medical Informatics, Biometry, and Epidemiology, University Hospital Essen, Essen, Germany; Department of Epidemiology, School of Public Health, Boston University, Boston, MA, USA. ·Lancet · Pubmed #30238891.

ABSTRACT: Cutaneous melanoma causes 55 500 deaths annually. The incidence and mortality rates of the disease differ widely across the globe depending on access to early detection and primary care. Once melanoma has spread, this type of cancer rapidly becomes life-threatening. For more than 40 years, few treatment options were available, and clinical trials during that time were all unsuccessful. Over the past 10 years, increased biological understanding and access to innovative therapeutic substances have transformed advanced melanoma into a new oncological model for treating solid cancers. Treatments that target B-Raf proto-oncogene serine/threonine-kinase (BRAF)

10 Review Survival of patients with advanced metastatic melanoma: the impact of novel therapies-update 2017. 2017

Ugurel, Selma / Röhmel, Joachim / Ascierto, Paolo A / Flaherty, Keith T / Grob, Jean Jacques / Hauschild, Axel / Larkin, James / Long, Georgina V / Lorigan, Paul / McArthur, Grant A / Ribas, Antoni / Robert, Caroline / Schadendorf, Dirk / Garbe, Claus. ·Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. Electronic address: selma.ugurel@uk-essen.de. · Bremen, Germany. · Melanoma, Immunotherapy and Innovative Therapy Unit, Istituto Nazionale Tumori Fondazione "G. Pascale", Naples, Italy. · Massachusetts General Hospital, Boston, MA, USA. · Department of Dermatology, Timone Hospital and Aix-Marseille University, Marseille, France. · Department of Dermatology, University Hospital of Schleswig-Holstein, Kiel, Germany. · Royal Marsden Hospital NHS Foundation Trust, London, UK. · Melanoma Institute Australia, The University of Sydney, and Royal North Shore Hospital, Sydney, NSW, Australia. · University of Manchester, The Christie NHS Foundation Trust, Manchester, UK. · Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia and University of Melbourne, Parkville, VIC, Australia. · University of California, Los Angeles, CA, USA. · Gustave Roussy Cancer Campus, Villejuif Grand-Paris, France. · Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. · Center for Dermatooncology, Department of Dermatology, University of Tuebingen, Tuebingen, Germany. ·Eur J Cancer · Pubmed #28756137.

ABSTRACT: The treatment of metastatic melanoma is still undergoing a process of major change. The two most important novel therapeutic strategies, selective kinase inhibitors and immune checkpoint blockers, both significantly prolong survival times of patients with advanced metastatic disease. Different agents, dose regimens and combinations have been tested against each other vigorously within these two groups. However, results from prospective head-to-head comparative studies of both strategies are still lacking. We performed an exploratory analysis of survival data from selected clinical trials representative for the new treatment strategies in advanced metastatic melanoma. Eighty-three Kaplan-Meier survival curves from 25 trials were digitised and grouped by therapeutic strategy and treatment line. For each of these groups, mean survival curves were generated for progression-free (PFS) and overall survival (OS) by weighted averaging. Survival curves grouped together by therapeutic strategy revealed a high concordance, particularly in the first-line setting. For kinase inhibitors, the most favourable PFS and OS in all therapy lines were observed for combined BRAF plus MEK inhibition. For immune checkpoint inhibitors, combined PD-1 plus CTLA-4 inhibition demonstrated the best survival outcome in all categories except for OS in first-line therapy. For the latter, combined PD-1 plus CTLA-4 inhibition showed similar outcomes as single-agent PD-1 inhibition. Comparison of kinase inhibitors and checkpoint blockers revealed a superiority of combined BRAF plus MEK inhibition within the first 6 months, later changing to a superiority of PD-1 blockers alone or in combination with CTLA-4 blockers. These results need confirmation by prospective clinical trials.

11 Review Advances in the Treatment of Advanced Extracutaneous Melanomas and Nonmelanoma Skin Cancers. 2017

Komatsubara, Kimberly M / Jeter, Joanne / Carvajal, Richard D / Margolin, Kim / Schadendorf, Dirk / Hauschild, Axel. ·From the Columbia University Medical Center, New York, NY; Ohio State University Medical Center, Columbus, OH; City of Hope, Duarte, CA; Department of Dermatology, University Hospital Essen, Essen, Germany; Department of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany. ·Am Soc Clin Oncol Educ Book · Pubmed #28561682.

ABSTRACT: Cutaneous malignancies make up the greatest proportion of all human cancers and include melanomas as well as nonmelanoma skin cancers (NMSCs) such as basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), as well as less common Merkel cell carcinoma (MCC), cutaneous lymphomas, cutaneous adnexal tumors, Kaposi sarcomas, and other sarcomas. Each of these NMSCs differ significantly in biology, clinical behavior, and optimal treatment recommendations from each other and from cutaneous melanoma. Similarly, less common extracutaneous melanomas, such as mucosal (MMs) and uveal (UMs), are unique biologic and clinical entities that require distinct diagnostic and management considerations. In this review, we summarize recent advances in biology and treatment of extracutaneous melanomas and NMSCs, including MMs, UMs, cSCC, BCC, and MCC.

12 Review Survival of patients with advanced metastatic melanoma: The impact of novel therapies. 2016

Ugurel, Selma / Röhmel, Joachim / Ascierto, Paolo A / Flaherty, Keith T / Grob, Jean Jacques / Hauschild, Axel / Larkin, James / Long, Georgina V / Lorigan, Paul / McArthur, Grant A / Ribas, Antoni / Robert, Caroline / Schadendorf, Dirk / Garbe, Claus. ·Department of Dermatology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany. Electronic address: selma.ugurel@uk-essen.de. · 28355 Bremen, Germany. · Melanoma, Immunotherapy and Innovative Therapy Unit, Istituto Nazionale Tumori, Fondazione "G. Pascale", Naples, Italy. · Massachusetts General Hospital, Boston, MA, USA. · Dermatology Department, Timone Hospital and Aix-Marseille University, Marseille, France. · University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany. · Royal Marsden Hospital NHS Foundation Trust, London, UK. · Melanoma Institute Australia and The University of Sydney, Sydney, NSW, Australia. · University of Manchester, The Christie NHS Foundation Trust, Manchester, UK. · Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia; University of Melbourne, Parkville, VIC, Australia. · University of California, Los Angeles, CA, USA. · Gustave Roussy Cancer Campus, Villejuif Grand-Paris, France. · Department of Dermatology, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany. · Center for Dermatooncology, Department of Dermatology, University Tuebingen, 72074 Tuebingen, Germany. ·Eur J Cancer · Pubmed #26707829.

ABSTRACT: The survival of advanced metastatic melanoma has been greatly improved within the past few years. New therapeutic strategies like kinase inhibitors for BRAF-mutant melanoma and immune checkpoint blockers proved to prolong survival times within clinical trials, and many of them have already entered routine clinical use. However, these different treatment modalities have not yet been tested against each other, which complicate therapy decisions. We performed an explorative analysis of survival data from recent clinical trials. Thirty-five Kaplan-Meier survival curves from 17 trials were digitised, re-grouped by matching inclusion criteria and treatment line, and averaged by therapy strategy. Notably, the survival curves grouped by therapy strategy revealed a very high concordance, even if different agents were used. The greatest survival improvement was observed with the combination of BRAF plus MEK inhibitors as well as with Programmed-death-1 (PD1) blockers with or without cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) blockers, respectively, with these two treatment strategies showing similar survival outcomes. For first-line therapy, averaged survival proportions of patients alive at 12 months were 74.5% with BRAF plus MEK inhibitor treatment versus 71.9% with PD-1 blockade. This explorative comparison shows the kinase inhibitors as similarly effective as immune checkpoint blockers with regard to survival. However, to confirm these first trends for implementation into an individualised treatment of melanoma patients, data from prospective clinical trials comparing the different treatment strategies head-to-head have to be awaited.

13 Review Melanoma. 2015

Schadendorf, Dirk / Fisher, David E / Garbe, Claus / Gershenwald, Jeffrey E / Grob, Jean-Jacques / Halpern, Allan / Herlyn, Meenhard / Marchetti, Michael A / McArthur, Grant / Ribas, Antoni / Roesch, Alexander / Hauschild, Axel. ·Department of Dermatology, University Duisburg-Essen, University Hospital Essen, Hufelandstrasse 55, 45147 Essen, Germany. · German Cancer Consortium (DKTK), Heidelberg, Germany. · Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. · Department of Dermatology, University Tübingen, Tübingen, Germany. · Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. · Department of Dermatology and Skin Cancers, APHM Timone Hospital Aix-Marseille University, Marseille, France. · Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. · Melanoma Research Center, Wistar Institute, Philadelphia, Pennsylvania, USA. · Division of Cancer Medicine and Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. · Departments of Medicine, Surgery, and Medical and Molecular Pharmacology, University of California Los Angeles, Los Angeles, California, USA. · Department of Dermatology, University Hospital Schleswig-Holstein (UKSH), Kiel, Germany. ·Nat Rev Dis Primers · Pubmed #27188223.

ABSTRACT: Melanoma is a common cancer in the Western world with an increasing incidence. Sun exposure is still considered to be the major risk factor for melanoma. The prognosis of patients with malignant (advanced-stage) melanoma differs widely between countries, but public campaigns advocating early detection have led to significant reductions in mortality rates. As well as sun exposure, distinct genetic alterations have been identified as associated with melanoma. For example, families with melanoma who have germline mutations in CDKN2A are well known, whereas the vast majority of sporadic melanomas have mutations in the mitogen-activated protein kinase cascade, which is the pathway with the highest oncogenic and therapeutic relevance for this disease. BRAF and NRAS mutations are typically found in cutaneous melanomas, whereas KIT mutations are predominantly observed in mucosal and acral melanomas. GNAQ and GNA11 mutations prevail in uveal melanomas. Additionally, the PI3K-AKT-PTEN pathway and the immune checkpoint pathways are important. The finding that programmed cell death protein 1 ligand 1 (PDL1) and PDL2 are expressed by melanoma cells, T cells, B cells and natural killer cells led to the recent development of programmed cell death protein 1 (PD1)-specific antibodies (for example, nivolumab and pembrolizumab). Alongside other new drugs - namely, BRAF inhibitors (vemurafenib and dabrafenib) and MEK inhibitors (trametinib and cobimetinib) - these agents are very promising and have been shown to significantly improve prognosis for patients with advanced-stage metastatic disease. Early signs are apparent that these new treatment modalities are also improving long-term clinical benefit and the quality of life of patients. This Primer summarizes the current understanding of melanoma, from mechanistic insights to clinical progress. For an illustrated summary of this Primer, visit: http://go.nature.com/vX2N9s.

14 Review Integrating first-line treatment options into clinical practice: what's new in advanced melanoma? 2015

Dummer, Reinhard / Schadendorf, Dirk / Ascierto, Paolo A / Larkin, James / Lebbé, Celeste / Hauschild, Axel. ·aDepartment of Dermatology, University Hospital Zürich, Zürich, Switzerland bDepartment of Dermatology, University Hospital Essen, Essen cDepartment of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany dIstituto Nazionale Tumori Fondazione 'G. Pascale', Naples, Italy eRoyal Marsden NHS Foundation Trust, London, UK fAPHP Oncodermatology Unit, University Paris 7 Diderot U976, Paris, France. ·Melanoma Res · Pubmed #26426764.

ABSTRACT: Melanoma remains a serious form of skin cancer in Europe and worldwide. Localized, early-stage melanomas can usually be treated with surgical excision. However, the prognosis is poorer for patients with advanced disease. Before 2011, treatment for advanced melanoma included palliative surgery and/or radiotherapy, and chemotherapy with or without immunotherapy, such as interleukin-2. As none of these treatments had shown survival benefits in patients with advanced melanoma, European guidelines had recommended that patients be entered into clinical trials. The lack of approved first-line options and varying access to clinical trials meant that European clinicians relied on experimental regimens and chemotherapy-based treatments when no other options were available. Since 2011, ipilimumab, an immuno-oncology therapy, and vemurafenib and dabrafenib, targeted agents that inhibit mutant BRAF, have been approved by the European Medicines Agency for the treatment of advanced melanoma. More recently, the MEK inhibitor, trametinib, received European marketing authorization for use in patients with BRAF mutation-positive advanced melanoma. In 2014, the anti-PD-1 antibody nivolumab was approved as a first-line therapy in Japan. Whereas nivolumab and another anti-PD-1 antibody, pembrolizumab, were approved as second-line therapies in the USA, their recent approval in Europe are for first-line use based on new clinical trial data in this setting. Together these agents are changing clinical practice and making therapeutic decisions more complex. Here, we discuss current and emerging therapeutic options for the first-line treatment of advanced melanoma, and how these therapies can be optimized to provide the best possible outcomes for patients.

15 Review Treatment algorithms in stage IV melanoma. 2015

Espinosa, Enrique / Grob, Jean-Jacques / Dummer, Reinhard / Rutkowski, Piotr / Robert, Caroline / Gogas, Helen / Kefford, Richard / Eggermont, Alexander M M / Martin Algarra, Salvador / Hauschild, Axel / Schadendorf, Dirk. ·1Service of Oncology, Hospital La Paz, Madrid, Spain · 2Department of Dermatology, Hopital Ste Marguerite, Marseille, France · 3Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland · 4Department of Sarcoma and Melanoma, M. Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland · 5Department of Dermatology (CR), and General Director (AE), Institute Gustave Roussy, Villejuif Cedex, France · 6First Department of Medicine, University of Athens Medical School, Athens, Greece · 7Department of Oncology, Westmead Hospital and Melanoma Institute Australia, University of Sydney, Sydney, Australia · 8Service of Oncology, Clinica Universitaria de Navarra, Pamplona, Spain · 9Department of Dermatology, University of Kiel, Kiel, Germany · and 10Department of Dermatology, University Hospital Essen, Essen, Germany. ·Am J Ther · Pubmed #24413374.

ABSTRACT: The molecular classification of melanoma and the advent of new drugs are changing the paradigm of therapy for advanced melanoma. A review of the recent key studies was performed, followed by a discussion in an expert forum. The aim of this review was to generate a therapeutic algorithm for stage IV melanoma. Tumor genotyping for BRAF and/or KIT should be performed before selection of therapy. For most BRAF-mutated melanoma patients and particularly those with a high tumor load, vemurafenib or other BRAF inhibitors such as dabrafenib are the treatment of choice. KIT inhibitors can be effective in KIT-mutant tumors, especially in those patients with mutations at exons 11 and 13. Ipilimumab is a good option for patients with nontargetable or nondetected mutations and those who progress under therapy with vemurafenib or a KIT inhibitor. There is still a role for conventional chemotherapy either as first-line treatment in BRAF wild-type patients or as salvage therapy in second or third line, or after other treatment modalities. Participation in clinical trials is strongly encouraged, either in first or in subsequent lines. New therapeutic options for advanced melanoma are guided by tumor genotyping. The current therapeutic algorithm includes kinase inhibitors, anti-CTLA4 therapy, immunotherapy, and chemotherapy, depending on the tumor genotype and response to previous treatments. Participation in clinical trials should always be encouraged because the treatment goal is long-term survival and potential cure in a subset of patients.

16 Review Side effects and toxicities of targeted therapies in stage IV melanoma. 2015

Ascierto, Paolo A / Bastholt, Lars / Hersey, Peter / Cinat, Gabriela / Eggermont, Alexander M M / Hauschild, Axel / Espinosa, Enrique / Robert, Caroline. ·1Unit of Melanoma, Cancer Immunotherapy and Innovative Therapy, Istituto Nazionale Tumori-Fondazione G. Pascale, Naples, Italy; 2Odense University Hospital, Odense, Denmark; 3Newcastle University, Newcastle, Australia; 4Instituto de Oncologia Angel Rolfo, Buenos Aires, Argentina; 5Institut Gustave Roussy, Villejuif, France; 6University of Kiel, Kiel, Germany; 7Hospital La Paz, Madrid, Spain; and 8Institut Gustave Roussy, Villejuif, France. ·Am J Ther · Pubmed #24185314.

ABSTRACT: As the incidence of melanoma continues to increase worldwide, the search for new therapies for advanced (stage IV) melanoma brings with it new patterns of toxicity to contend with. This review covers the toxicity profiles of new treatments for advanced melanoma currently in development. Therefore, the latest literature on melanoma treatment was surveyed for data on reported toxicities. The new types of treatments can be roughly divided into targeted tyrosine kinase inhibitors and immunomodulating agents. Each has its own set of toxicities particular to type and to individual drug. Targeted tyrosine kinase inhibitors generally cause fatigue, whereas immunomodulatory agents induce a specific set of adverse events known as immune-related adverse events (irAEs). Despite the incidence of adverse events, these agents hold promise for the treatment of stage IV melanoma. With new treatment opportunities come increased chance of toxic reactions. The key to successful melanoma treatment in the future is likely to be novel combinations of new therapeutic agents.

17 Review Who benefits most from adjuvant interferon treatment for melanoma? 2015

Gogas, Helen / Abali, Huseyin / Ascierto, Paolo A / Demidov, Lev / Pehamberger, Hubert / Robert, Caroline / Schachter, Jacob / Eggermont, Alexander M M / Hauschild, Axel / Espinosa, Enrique. ·1First Department of Medicine, Athens University Medical School, Athens, Greece; 2Division of Medical Oncology, Baskent University School of Medicine, Adana, Turkey; 3Unit of Medical Oncology and Innovative Therapy, Istituto Nazionale Tumori Fondazione "G. Pascale," Naples, Italy; 4Department of Biotherapy, Blokhin Cancer Center, Moscow, Russia; 5Department of Dermatology, Medical University of Vienna, Vienna, Austria; 6Department of Dermatology, Institute Gustave Roussy, Villejuif Cedex, France; 7Department of Oncology, Sheba Medical Center, Tel Hashomer, Israel; 8Department of Dermatologie, University of Kiel, Kiel, Germany; and 9Oncology Service, Hospital La Paz, Madrid, Spain. ·Am J Ther · Pubmed #24176884.

ABSTRACT: Metastatic melanoma has a poor prognosis; the median survival for patients with stage IV melanoma ranges from 8 to 18 months after diagnosis. Interferon-α provides significant improvement in disease-free survival at the cost of poor tolerability. Identifying patients who benefit the most may improve the cost:benefit ratio. In addition, no data exist for the role of adjuvant therapy in noncutaneous melanoma. Molecular profiles may help to identify patients who benefit the most from adjuvant interferon therapy. In this review, the American Joint Commission on Cancer 2009 staging criteria and emerging biomarker data to guide adjuvant treatment decisions will be discussed. Several criteria to guide selection of patients are discussed in detail. These include Breslow thickness, number of positive lymph nodes, whether or not the primary lesion has ulcerated, immunologic markers, and cytokine profiles. Substantial progress has been made in deciding which patients benefit from interferon-α adjuvant therapy. Interferon-α is the only agent currently approved for the adjuvant treatment of this deadly disease, despite its side effect profile. More effective drugs with better tolerability are needed.

18 Review Frontline approach to metastatic BRAF-mutant melanoma diagnosis, molecular evaluation, and treatment choice. 2014

Chapman, Paul B / Hauschild, Axel / Sondak, Vernon K. ·From the Memorial Sloan-Kettering Cancer Center, New York, NY; Universitätsklinikum Schleswig-Holstein, Kiel, Germany; Department of Cutaneous Oncology, Moffitt Cancer Center, and Departments of Oncologic Sciences and Surgery, University of South Florida, Tampa, FL. ·Am Soc Clin Oncol Educ Book · Pubmed #24857132.

ABSTRACT: An estimated 76,100 patients will be diagnosed with invasive melanoma in the United States in 2014, and 9,710 patients will die from the disease. In almost all cases, the cause of death is related to the development of widespread metastatic disease. Although death rates from most types of cancer have steadily decreased in the United States--a 20% decrease during two decades from a peak of 215.1 deaths per 100,000 population in 1991 to 171.8 in 2010--death rates from melanoma have steadily increased during the same time, especially among males. The news regarding melanoma is far from all bad. Increases in our understanding of the human immune system have led to the development of new immunotherapeutic drugs such as ipilimumab, which has been shown to improve survival in phase III trials in metastatic melanoma, and anti-programmed death 1 (anti-PD1) antibodies, recently hailed by ASCO as one of the past year's most noteworthy clinical cancer advances. However, no discovery has influenced and, indeed, transformed the management of metastatic melanoma more than the identifıcation of activating mutations in the BRAF gene in the mitogen-activated protein kinase (MAPK) pathway, which occur in about half of cutaneous melanomas and can be targeted with small molecule inhibitors of the BRAF protein, the downstream MEK protein, or both. This article will address how patients with metastatic melanoma are evaluated for their mutation status and how the presence of a targetable mutation influences therapeutic decisions regarding systemic therapy and even surgery.

19 Review Ipilimumab in patients with cancer and the management of dermatologic adverse events. 2014

Lacouture, Mario E / Wolchok, Jedd D / Yosipovitch, Gil / Kähler, Katharina C / Busam, Klaus J / Hauschild, Axel. ·Memorial Sloan Kettering Cancer Center, New York, New York; Weill-Cornell Medical College, New York, New York. Electronic address: lacoutum@mskcc.org. · Memorial Sloan Kettering Cancer Center, New York, New York; Weill-Cornell Medical College, New York, New York; Ludwig Institute for Cancer Research, New York, New York. · Departments of Dermatology, Neurobiology and Anatomy, and Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina. · Department of Dermatology, University of Kiel, Kiel, Germany. · Memorial Sloan Kettering Cancer Center, New York, New York. ·J Am Acad Dermatol · Pubmed #24767731.

ABSTRACT: Ipilimumab is a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 to augment antitumor T-cell responses. Phase III studies have demonstrated survival benefit in both previously treated and treatment-naïve patients with metastatic melanoma. In clinical trials, adverse events (AEs) related to treatment with ipilimumab were mostly grade 1/2 (as per Common Terminology Criteria for AEs, Version 4.02), and mostly reversible with appropriate management. Distinct immune-related AEs that may reflect the mechanism of action of ipilimumab have been identified, and occur commonly in the skin, typically presenting as a maculopapular rash, which can be accompanied by pruritus, pruritus with no skin lesions, alopecia, and vitiligo. Histologic analyses have revealed epidermal spongiosis, and perivascular CD4(+) T-cell infiltrates with some eosinophils in areas of rash. Timely implementation of toxicity-specific treatment guidelines that emphasize vigilance and early intervention allows mitigation of dermatologic AEs. Adherence to guidelines is necessary to maintain quality of life, ensure consistent dosing, and obtain the best possible clinical outcome.

20 Review Melanoma in 2013: Melanoma--the run of success continues. 2014

Schadendorf, Dirk / Hauschild, Axel. ·Department of Dermatology, University Duisburg-Essen, University Hospital Essen, Hufelandstrasse 55, 45147 Essen, Germany. · Departments of Dermatology, University Hospital Schleswig-Holstein (UKSH), Campus Kiel, Schittenhelmstrasse 7, 24105 Kiel, Germany. ·Nat Rev Clin Oncol · Pubmed #24419300.

ABSTRACT: -- No abstract --

21 Review Adjuvant interferon alfa in malignant melanoma: an interdisciplinary and multinational expert review. 2013

Ascierto, Paolo A / Gogas, Helen J / Grob, Jean Jacques / Algarra, Salvador Martín / Mohr, Peter / Hansson, Johan / Hauschild, Axel. ·Unit of Melanoma, Cancer Immunotherapy and Innovative Therapy, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale," Naples, Italy. paolo.ascierto@gmail.com ·Crit Rev Oncol Hematol · Pubmed #22874771.

ABSTRACT: Interferon alfa (IFNα) and pegylated IFNα2b (PegIFNα2b) are the only agents currently approved for the adjuvant treatment of resected melanoma at high risk of recurrence. Meta-analyses showed statistically significant disease-free survival (DFS) and overall survival (OS) benefits versus controls but did not clarify optimal dose/duration. We review data from all recent clinical trials to provide the latest information on dose, duration, and potential predictive factors of treatment success. Recent data largely confirm DFS and OS benefits but optimal dose/duration is not clarified. The data suggest greater responses in patients with stage III micro-metastatic versus macro-metastatic disease, and ulceration may also predict greater sensitivity to therapy, although further investigation is needed. Presently, IFNα and PegIFNα2b remain valid adjuvant therapies following resection of high-risk melanoma; the most appropriate treatment regimen should be determined on an individual patient basis according to patient lifestyle and approach, potential for toxicity, and the available clinical evidence.

22 Review Progression of cutaneous melanoma: implications for treatment. 2012

Leong, Stanley P L / Mihm, Martin C / Murphy, George F / Hoon, Dave S B / Kashani-Sabet, Mohammed / Agarwala, Sanjiv S / Zager, Jonathan S / Hauschild, Axel / Sondak, Vernon K / Guild, Valerie / Kirkwood, John M. ·Center for Melanoma Research and Treatment and Department of Surgery, California Pacific Medical Center, San Francisco, CA, USA. leongsx@cpmcri.org ·Clin Exp Metastasis · Pubmed #22892755.

ABSTRACT: The survival rates of melanoma, like any type of cancer, become worse with advancing stage. Spectrum theory is most consistent with the progression of melanoma from the primary site to the in-transit locations, regional or sentinel lymph nodes and beyond to the distant sites. Therefore, early diagnosis and surgical treatment before its spread is the most effective treatment. Recently, new approaches have revolutionized the diagnosis and treatment of melanoma. Genomic profiling and sequencing will form the basis for molecular taxonomy for more accurate subgrouping of melanoma patients in the future. New insights of molecular mechanisms of metastasis are summarized in this review article. Sentinel lymph node biopsy has become a standard of care for staging primary melanoma without the need for a more morbid complete regional lymph node dissection. With recent developments in molecular biology and genomics, novel molecular targeted therapy is being developed through clinical trials.

23 Review Management of pegylated interferon alpha toxicity in adjuvant therapy of melanoma. 2012

Daud, Adil / Soon, Christopher / Dummer, Reinhard / Eggermont, Alexander M M / Hwu, Wen-Jen / Grob, Jean Jacques / Garbe, Claus / Hauschild, Axel. ·University of California, San Francisco, Melanoma Program, San Francisco 1600 Divisadero St, Rm A741, Box 1770, San Francisco, CA 94115, USA. adaud@medicine.ucsf.edu ·Expert Opin Biol Ther · Pubmed #22694288.

ABSTRACT: INTRODUCTION: Both native IFNα2b and pegylated IFNα2b (PegIFNα2b) are approved for the adjuvant treatment of high-risk melanoma. AREAS COVERED: This review compares the toxicity profiles of high-dose IFNα2b (HDI) and PegIFNα2b, and provides recommendations on the management of common PegIFNα2b-related toxicities, based on available clinical data and published literature. EXPERT OPINION: The toxicity profile of PegIFNα2b at the approved dose (6 μg/kg/week for 8 weeks then 3 μg/kg/week for up to 5 years) is qualitatively similar to HDI in melanoma. The most common adverse events (AEs) are fatigue, anorexia, hepatotoxicity, flu-like symptoms, injection site reactions and depression. However, fatigue and flu-like symptoms appear less severe with PegIFNα2b, and toxicity seems to occur earlier, whereas with HDI toxicity may increase with time. Most AEs can be managed effectively by dose modification and aggressive symptom control. Dosing to tolerance using a three-step dose reduction schedule to maintain an ECOG performance status of 0 - 1 may enable patients experiencing toxicity to remain on treatment; this can be applied readily in clinical practice. PegIFNα2b is therefore a valuable alternative option for adjuvant treatment in melanoma, with a toxicity profile similar to that of HDI overall but a more convenient administration schedule.

24 Review Management of immune-related adverse events and kinetics of response with ipilimumab. 2012

Weber, Jeffrey S / Kähler, Katharina C / Hauschild, Axel. ·H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA. jeffrey.weber@moffitt.org ·J Clin Oncol · Pubmed #22614989.

ABSTRACT: Monoclonal antibodies directed against the immune checkpoint protein cytotoxic T-lymphocyte antigen-4 (CTLA-4; CD152)-ipilimumab and tremelimumab-have been investigated in metastatic melanoma and other cancers and have shown promising results. Recently, ipilimumab was approved by the US Food and Drug Administration for the treatment of metastatic melanoma. We review the literature on managing the adverse effects and kinetics of tumor regression with ipilimumab and provide guidelines on their management. During treatment with these antibodies, a unique set of adverse effects may occur, called immune-related adverse events (irAEs). These include rashes, which may rarely progress to life-threatening toxic epidermal necrolysis, and colitis, characterized by a mild to moderate, but occasionally also severe and persistent diarrhea. Hypophysitis, hepatitis, pancreatitis, iridocyclitis, lymphadenopathy, neuropathies, and nephritis have also been reported with ipilimumab. Early recognition of irAEs and initiation of treatment are critical to reduce the risk of sequelae. Interestingly, irAEs correlated with treatment response in some studies. Unique kinetics of response have been observed with CTLA-4 blockade with at least four patterns: (1) response in baseline lesions by week 12, with no new lesions seen; (2) stable disease, followed by a slow, steady decline in total tumor burden; (3) regression of tumor after initial increase in total tumor burden; and (4) reduction in total tumor burden during or after the appearance of new lesion(s) after week 12. We provide a detailed description of irAEs and recommendations for practicing oncologists who are managing them, along with the unusual kinetics of response associated with ipilimumab therapy.

25 Review Mucosal melanomas of the head and neck: new aspects of the clinical outcome, molecular pathology, and treatment with c-kit inhibitors. 2011

Papaspyrou, Giorgios / Garbe, Claus / Schadendorf, Dirk / Werner, Jochen A / Hauschild, Axel / Egberts, Friederike. ·Department of Otolaryngology, Head and Neck Surgery, Philipps University Marburg, Marburg, Germany. ·Melanoma Res · Pubmed #21897303.

ABSTRACT: Approximately 50% of mucosal melanomas affect the head and neck region representing approximately 9% of all malignant head and neck tumors. The pathogenesis of this disease is unknown. Mucosal melanomas are characterized by an aggressive biological behavior, leading to a 5-year survival rate of less than 25%. Data for this review were identified by searches of Medline, Current Contents, PubMed, and references from relevant articles using the terms 'mucosal melanoma,' 'head and neck melanoma,' 'c-kit mutation in melanoma,' and 'c-kit inhibitors'. Therapy aims for the complete surgical excision of the primary tumor, whereas sentinel node biopsy is not established and present data do not support the addition of radiotherapy. Mutilating operations of larger tumors should be avoided, as they do not inhibit the frequent development of distant metastasis. C-kit mutations and amplifications are found in approximately 15-30% of mucosal and acral-lentiginous melanomas. Therefore, the use of so-called targeted therapies addressing molecular structures in mucosal melanomas seem to represent new promising treatment tools. In this study, we review the literature regarding epidemiology, molecular pathology, and therapy of mucosal melanomas of the head and neck emphasizing c-kit protein inhibiting treatment modalities for tumors carrying c-kit mutations.

Next