The introduction in clinical practice of new drug compounds both targeted therapies anti-BRAF and checkpoint inhibitors have largely improved our potential to manage advanced metastatic melanoma ...patients. This has led to a significant improvement in terms of response rates and particularly in the overall survival (OS). The long-term results of trials with follow-up data of patients treated with targeted or immunotherapies reported median OS rates around 24 months, with 5-year survival rates around 35-40%. As to the drugs currently available and reimbursed by the Italian National Health System, 3 combinations of anti-BRAF/anti-MEK inhibitors are available (dabrafenib/trametinib, vemurafenib/cobimetinib and the most recently introduced encorafenib/binimetinib). As for checkpoint inhibitors, first line immunotherapy is represented by anti-PD1 blockers (nivolumab and pembrolizumab), whilst the anti-CTLA-4 ipilimumab can be used as second line immunotherapy. The decision-making factors that define the best treatment approach in stage IV patients with metastatic melanoma include the mutation pattern, performance status, high/low tumor load, brain metastases, progression pattern (low/fast), and availability of clinical trials. This review will analyze the current therapeutic tools adopted for the treatment of metastatic melanoma patients. It will then focus on the latest results obtained by novel treatments (checkpoint inhibitors and targeted therapies) which can be used in the clinical daily practice.
Ipilimumab and Nivolumab are novel monoclonal antibodies that have recently been used successfully for treatment of metastatic melanoma. Ipilimumab is a human monoclonal antibody against Cytotoxic T ...Lymphocyte Antigen 4 (CTLA4) receptor, which suppresses T-cell proliferation and stimulates an inflammatory response against cancer cells. Nivolumab is an IgG4 monoclonal antibody against the cytotoxic T lymphocyte associated programmed death 1 receptor (PD-1). Ipilimumab and Nivolumab combination treatment has been shown to induce remission and prolong survival in patients with metastatic melanoma. The side effect profile of these medications has not been well studied. One entity of the side effects reported in the literature is immune-related adverse events (irAEs). There have been few case reports where these events were serious and irreversible. In this case report, we describe a fatal and severe diffuse panmyositis that involved the cardiac, respiratory, and extraocular muscles in a patient with metastatic melanoma secondary to combination treatment with Ipilimumab/Nivolumab.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract
The notion of treating the patient, and not the particular disease, has been emphasized by physicians for some time. In the past decade, this idea advanced with the human genome project, and ...has been taken further with the advent of personalized dermatology, or using genetics to drive pharmacological treatment. For example, recent melanoma treatment trials focus entirely on the genetic makeup of the individual. Although some dermatological conditions such as melanoma are being targeted with gene-specific therapy, the idea of choosing a drug based on the genetic makeup to treat other dermatologic conditions might be relevant, since it may increase drug efficacy or decrease adverse drug events. This concept of pharmacogenomics could be applied throughout the field of dermatology. Online libraries have been developed to guide drug efficacy, dose prediction and adverse events. We provide a list of current systemic dermatologic drugs in which the pharmacokinetics and pharmacodynamics have been studied. It would be beneficial to guide patient treatment with these drugs, if we can better understand their pharmacogenomics.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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