Współistnienie zespołu ręka–stopa i rozległych zmian rumieniowo- -obrzękowych – skórne działania niepożądane po sorafenibie

Wprowadzenie: Zespół ręka–stopa (erytrodyzestezja dłoniowo-podeszwowa)to dermatoza wywoływana przez toksyczne działanie niektórychchemioterapeutyków i leków biologicznych na skórę, objawiającasię zmianami rumieniowymi, hiperkeratozą i pęcherzami zlokalizowanymigłównie na dłoniach i podeszwach. Zespół ten jest jednym z najczęściejwystępujących objawów ubocznych u pacjentów leczonychsorafenibem – inhibitorem kinaz tyrozynowych o działaniu antyangiogennymi antyproliferacyjnym. Rzadko opisywano współistnieniezespołu ręka–stopa ze zmianami rumieniowymi. Cel pracy: Przedstawienie obrazu klinicznego toksycznego działaniasorafenibu na skórę, w związku z coraz częstszym stosowaniem chemioterapeutykówz grupy inhibitorów kinaz. Opis przypadku: Przedstawiono 71-letnią kobietę leczoną sorafenibemz powodu rozsianego raka nerki, u której stwierdzono objawy erytrodyzestezjidłoniowo-podeszwowej współistniejące z rozległymi zmianamirumieniowymi, rozwijającymi się po 6 dniach stosowania leku.W terapii zastosowano kortykosteroidy ogólne, leki przeciwhistaminoweoraz leczenie miejscowe preparatami kortykosteroidowymii maściami z mocznikiem, a także zmniejszono dawkę chemioterapeutykuo połowę, uzyskując poprawę stanu skóry. Wnioski: Nowoczesne terapie przeciwnowotworowe charakteryzująsię dużym potencjałem toksycznym w stosunku do skóry, co stanowiwyzwanie nie tylko dla onkologów, ale także dla dermatologów

The Variations’ in Genes Encoding TIM-3 and Its Ligand, Galectin-9, Influence on ccRCC Risk and Prognosis

Renal cell cancer is the most common type of kidney cancer in adults, and clear cell renal cell carcinoma (ccRCC) is the most diagnosed type. T cell immunoglobulin and mucin-domain-containing-3 (TIM-3) belongs to immunological checkpoints that are key regulators of the immune response. One of the known TIM-3 ligands is galectin-9 (LGALS9). A limited number of studies have shown an association between TIM-3 polymorphisms and cancer risk in the Asian population; however, there is no study on the role of LGALS9 polymorphisms in cancer. The present study aimed to analyze the influence of TIM-3 and LGALS9 polymorphisms on susceptibility to ccRCC and patient overall survival (OS), with over ten years of observations. Using TaqMan probes, ARMS–PCR, and RFPL-PCR, we genotyped two TIM-3 single-nucleotide polymorphisms (SNPs): rs1036199 and rs10057302, and four LGALS9 SNPs: rs361497, rs3751093, rs4239242, and rs4794976. We found that the presence of the rs10057302 A allele (AC + AA genotypes) as well as the rs4794976 T allele (GT + TT genotypes) decreased susceptibility to ccRCC by two-fold compared to corresponding homozygotes. A subgroup analysis showed the association of some SNPs with clinical features. Moreover, TIM-3 rs1036199 significantly influenced OS. Our results indicate that variations within TIM-3 and LGALS9 genes are associated with ccRCC risk and OS

Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma

International audienceBACKGROUND The role of adjuvant treatment in high-risk muscle-invasive urothelial carcinoma after radical surgery is not clear. METHODS In a phase 3, multicenter, double-blind, randomized, controlled trial, we assigned patients with muscle-invasive urothelial carcinoma who had undergone radical surgery to receive, in a 1:1 ratio, either nivolumab (240 mg intravenously) or placebo every 2 weeks for up to 1 year. Neoadjuvant cisplatin-based chemotherapy before trial entry was allowed. The primary end points were disease-free survival among all the patients (intention-to-treat population) and among patients with a tumor programmed death ligand 1 (PD-L1) expression level of 1% or more. Survival free from recurrence outside the urothelial tract was a secondary end point. RESULTS A total of 353 patients were assigned to receive nivolumab and 356 to receive placebo. The median disease-free survival in the intention-to-treat population was 20.8 months (95% confidence interval [CI], 16.5 to 27.6) with nivolumab and 10.8 months (95% CI, 8.3 to 13.9) with placebo. The percentage of patients who were alive and disease-free at 6 months was 74.9% with nivolumab and 60.3% with placebo (hazard ratio for disease recurrence or death, 0.70; 98.22% CI, 0.55 to 0.90; P<0.001). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 74.5% and 55.7%, respectively (hazard ratio, 0.55; 98.72% CI, 0.35 to 0.85; P<0.001). The median survival free from recurrence outside the urothelial tract in the intention-to-treat population was 22.9 months (95% CI, 19.2 to 33.4) with nivolumab and 13.7 months (95% CI, 8.4 to 20.3) with placebo. The percentage of patients who were alive and free from recurrence outside the urothelial tract at 6 months was 77.0% with nivolumab and 62.7% with placebo (hazard ratio for recurrence outside the urothelial tract or death, 0.72; 95% CI, 0.59 to 0.89). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 75.3% and 56.7%, respectively (hazard ratio, 0.55; 95% CI, 0.39 to 0.79). Treatment-related adverse events of grade 3 or higher occurred in 17.9% of the nivolumab group and 7.2% of the placebo group. Two treatment-related deaths due to pneumonitis were noted in the nivolumab group. CONCLUSIONS In this trial involving patients with high-risk muscle-invasive urothelial carcinoma who had undergone radical surgery, disease-free survival was longer with adjuvant nivolumab than with placebo in the intention-to-treat population and among patients with a PD-L1 expression level of 1% or more

Treatment of muscle-invasive urothelial cancer with nivolumab (CheckMate 274 study): a plain language summary

International audienceWhat is this summary about? This is a summary of a paper published in a medical journal that describes the results of a study called CheckMate 274. This study looked at a new treatment for muscle-invasive urothelial cancer, a type of cancer found in the urinary tract that has spread from the inner lining of the urinary tract or bladder and into the surrounding muscle wall where it can then spread to other parts of the body. The standard treatment for muscle-invasive urothelial cancer is surgery to remove affected parts of the urinary tract. However, cancer returns in more than half of people after this surgery. Adjuvant therapy is given to people after surgery with muscle-invasive urothelial cancer with a goal to reduce the risk of the cancer coming back; however, at the time this study started, there was no standard adjuvant treatment. What happened in the study? In the CheckMate 274 study, researchers compared nivolumab with a placebo as an adjuvant treatment for people with muscle-invasive urothelial cancer. The aim of the study was to understand how well nivolumab worked to reduce the chance of the cancer returning after surgery. The study also looked at what side effects (unwanted or unexpected results or conditions that are possibly related to the use of a medication) people had with treatment. What do the results mean? The results showed that people who received nivolumab versus placebo: Survived longer before the cancer was detected again, including people who had programmed death ligand-1 (shortened to PD-L1) on their cancer cells. Survived longer before a secondary cancer outside of the urinary tract was detected. Experienced no differences in health-related quality of life (the impact of the treatment on a person's mental and physical health). Had similar side effects to the people who received nivolumab in other studies