Witold Owczarek

Management of dermatological adverse events during nivolumab treatment

Programmed death 1 receptor (PD-1) inhibitors, such as nivolumab, are effective in the treatment of advanced and metastatic melanoma, as well as in kidney, bladder, and non-small cell lung carcinomas. Adverse events of PD-1 inhibitors result mostly from autoimmune mechanisms, include gastrointestinal inflammatory diseases, hepatotoxicity, neurotoxicity, endocrinopathies, and skin toxicities. In this article, we highlight the main cutaneous adverse events associated with PD-1 inhibitors and provide a set of practical guidelines about their management. Additionally, we report a case of nivolumab-induced bullous pemphigoid in a patient with metastatic melanoma.

The direct costs of drug-induced skin reactions

[b] Abstract Objective.[/b] The aim of the study was an assessment of direct costs of patients hospitalised for for skin adverse drug reactions during 2002-2012 in the Department of Dermatology at the Military Institute of Medicine (Ministry of Defence) in Warsaw. The analysis was carried out from the perspectives of the public payer and service provider. [b]Materials and method. [/b]The retrospective study was carried out in a group of 164 adult patients due to skin adverse drug reactions. Analysis was based on data from patient medical records and medical orders which provided information on the used resources, including diagnostic tests, medical consultations, medicinal products, hospitalisation duration, together with cost estimation, regardless of the treatment being the cause of the skin reaction. [b]Results[/b]. According to the International Statistical Classification of Diseases and Related Health Problems(ICD) diagnosis and scores, assigned by the National Healthcare Fund, it has been estimated that patient hospitalisation at the Department of Dermatology for skin drug reaction incurred costs at the average amount of €717.00 per patient. The complex diagnostics and pharmacotherapy of the same group of patients generated costs for the hospital at the average amount of €680 per patient. [b]Conclusions[/b]. As a result of the analysis, the therapy for skin adverse drug effects generates significant costs, both for the payer and the service provider. Since the costs are comparable, it seems that the pricing of medical procedures by the public payer is adequate for the costs incurred by the medical service provider.

The incidence and management of cutaneous adverse events of the epidermal growth factor receptor inhibitors

Overexpression of the epidermal growth factor receptor (EGFR) is found in many cancers, including those of the head and neck area, non-small-cell lung cancer, and colorectal, cervical, prostate, breast, ovary, stomach, and pancreatic cancer. The EGFR inhibitors are used at present in the treatment of such cancers. Skin lesions that develop during and after cancer treatment may be due to specific cytostatics, molecular-targeted drugs, radiation therapy, complementary therapy, or the cancer itself, and hence knowledge is essential to distinguish between them. The mechanism through which skin toxicity arises during treatment with EGFR inhibitors is not well known, but seems to be due to the modification of the RAS/RAF/MEK/ERK signal path associated with its activation, which results in the similarity between the adverse effects of EGFR inhibitors and the treatment of melanoma with BRAF and MEK inhibitors. The most common side effects are pruritus, xerosis, papulopustular rash, hand-foot skin reaction, alopecia and dystrophy of the hair, and paronychia. This work presents options for prevention and suggestions for managing these adverse events, which are of importance in the care of patients undergoing oncological treatment.

Recommendations for diagnosis and therapy of cutaneous melanoma

Podstawą klinicznej diagnostyki roznicowej czerniakow skory i kwalifikacji do biopsji wycinającej jest obecnie dermoskopia. Dla ustalenia rozpoznania i określenia najwazniejszych czynnikow rokowniczych podstawowe znaczenie ma biopsja wycinająca podejrzanych w kierunku wczesnego czerniaka zmian barwnikowych skory (wyciecie calej grubości skory i powierzchownej warstwy tkanki tluszczowej). Wczesne rozpoznanie i chirurgiczne usuniecie czerniaka nie tylko poprawia rokowanie, ale daje szanse wyleczenia okolo 90% chorych. Kolejne etapy postepowania terapeutycznego obejmują kwalifikacje chorych do radykalnego wyciecia blizny po biopsji wycinającej z wlaściwymi marginesami oraz wykonania biopsji wezla wartowniczego. W przypadku przerzutow do regionalnych wezlow chlonnych postepowaniem z wyboru jest wykonanie radykalnej limfadenektomii. Zaleca sie wlączanie chorych na czerniaki skory o wysokim ryzyku nawrotu (przerzuty do wezlow chlonnych i/lub owrzodzenie pierwotnej zmiany) do prospektywnych badan klinicznych nad leczeniem uzupelniającym. Obecnośc przerzutow odleglych wiąze sie ze zlym rokowaniem. W sytuacji uogolnienia nowotworu konieczne jest wykonanie badania w kierunku mutacji genu BRAF . Dlugoletnie przezycia dotyczą glownie chorych poddanych resekcji pojedynczych ognisk przerzutowych. W systemowym leczeniu — przede wszystkim pierwszej linii — u chorych z obecnością mutacji BRAF V600 znajduje zastosowanie inhibitor BRAF — wemurafenib lub dabrafenib (preferencyjnie w skojarzeniu z inhibitorem MEK) oraz — niezaleznie od statusu mutacji BRAF — immunoterapia przeciwcialami anty-PD-1 (niwolumab lub pembrolizumab), ewentualnie ipilimumab (przeciwcialo anty-CTLA4).

Diagnosis and treatment of basal cell and squamous cell carcinoma and melanoma of the skin recommended by the Oncology Section of the Polish Dermatology Society as well as the Melanoma Academy Section of the Polish Society of Oncological Surgery

Basal cell carcinoma (BCC) as well as the squamous cell carcinoma (SCC) are the most frequent malignant neoplasms among Caucasian patients. Despite the fact, that they seldom metastasise and are not directly fatal, they constitute a significant clinical issue. Such cancers infiltrate surrounding tissues and destroy the surrounding structures, e.g., bones and cartilages. This results in such structures developing severe defects and significantly reduces the quality of life of the patients. Those with chronic immunosuppresion or a genetic predisposition to develop UV-induced skin cancer are at risk of dying, particularly if the cancer is aggressive. The Oncology Department of the Polish Dermatology Society (Polish: Sekcja Onkologiczna Polskiego Towarzystwa Dermatologicznego — PTD) as well as the Melanoma Academy Department of the Polish Society of Oncological Surgery (Polish: sekcja Akademia Czerniaka Polskiego Towarzystwa Chirurgii Onkologicznej — PTChO), basing on the current European guidelines, American recommendations of the National Comprehensive Cancer Network (revision 1.2015) and interventional reviews of publications elaborated by the Cochrane Skin Group, attempted to systemise the diagnostic and therapeutic procedures and o determine rules for primary and secondary prevention in patients suspected/diagnosed with a basal cell or squamous cell carcinoma. The paper presents recommendations regarding diagnosis and treatment of skin cancers, taking all related benefits and challenges into consideration, as well as recommendations for post treatment patients monitoring.

The Polish Expert Group Position Statement on The Safety of Biological Treatments with Monoclonal Antibodies and Fusion Proteins

Objective: The first biological therapeutics have already reached their patent expiration dates and corresponding biosimilars have been approved by the EMA and FDA. The approval of products similar, but not identical to already known innovative biologics is stirring a lot of debate about safety concerns, as well as the relevance of these differences to clinical practice. Methods: A Group of 13 experts involved in various aspects of biological therapies in Poland was established. Modified Delphi method of voting was performed to achieve consensus regarding the most important aspects of biological

Leczenie biologiczne łuszczycy w Polsce

Psoriasis biological treatment in Poland Biologics are an important, but expensive treatment option in certain inflammatory diseases. Psoriasis is chronic disease that is a major public health problem in all countries. The paper shows the practical applicability of biological agents in this disease therapy. Many aspects of the clinical, cost and availability of biological treatment of psoriasis in Poland were discussed.