Population pharmacokinetics of rotigotine extended-release microspheres for intramuscular injection in patients with early-stage Parkinson's disease.

AIMS: Rotigotine extended-release microspheres is a weekly intramuscular injection formulation to treat Parkinson's disease. This study aimed to develop a population pharmacokinetics (PK) model for rotigotine extended-release microspheres to investigate its PK ethnic differences. METHODS: Data for the study were obtained from three studies in China, Japan and the US. The population PK model was developed using the Phoenix NLME 8.3.5 software. Two parallel absorption models were created to include both zero- and first-order absorptions. The elimination phase was evaluated for one- and two-compartment linear models. Moreover, covariates including sex, body weight, body mass index, albumin, creatinine clearance and race were input into the model using a stepwise covariate method. RESULTS: We constructed a one-compartment linear model with the first parallel absorption model identified as the best-fitting model. Simulation results in patients with lighter body weight (45 kg) exhibited a 27% increase in Cmax,ss and a 31% increase in AUCtau,ss compared to those with median body weight (65 kg). Patients with heavier body weight (103 kg) showed a 27% decrease in Cmax,ss and a 29% decrease in AUCtau,ss compared to the median body weight group. Asian patients displayed only a 21% increase in Cmax,ss and a 6% increase in AUCtau,ss compared to non-Asian. While we could not fully conclude that race does not affect rotigotine exposure, dosage adjustments based on race were not deemed necessary. CONCLUSIONS: Exposure differences were mainly attributed to body weight, while dose adjustments were not needed for patients of different racial identities.

Experience With Bexarotene to Treat Cutaneous T-Cell Lymphomas: A Study of the Spanish Working Group of Cutaneous Lymphomas.

BACKGROUND AND OBJECTIVES: Bexarotene has been approved to treat advanced stage cutaneous T-cell lymphomas (CTCL) since 1999. However, very few data have been published on its long-term safety and efficacy profile. The aim of this study is to determine the tolerability to bexarotene and outcomes by collecting the 2nd largest case series to date on its long-term use vs CTCL. MATERIAL AND METHOD: This was a multicenter retrospective review of 216 patients with mycosis fungoides (174), or Sézary syndrome (42) on a 10-year course of bexarotene alone or in combination with other therapies at 19 tertiary referral teaching hospitals. RESULTS: A total of 133 men (62%) and 83 women (38%) were included, with a mean age of 63.5 year (27-95). A total of 45% were on bexarotene monotherapy for the entire study period, 22% started on bexarotene but eventually received an additional therapy, 13% were on another treatment but eventually received bexarotene while the remaining 20% received a combination therapy since the beginning. The median course of treatment was 20.78 months (1-114); and the overall response rate, 70.3%. Complete and partial response rates were achieved in 26% and 45% of the patients, respectively. Treatment was well tolerated, being the most common toxicities hypertriglyceridemia (79%), hypercholesterolemia (71%), and hypothyroidism (52%). No treatment-related grade 5 adverse events were reported. CONCLUSIONS: Our study confirms bexarotene is a safe and effective therapy for the long-term treatment of CTCL.

Experience With Bexarotene to Treat Cutaneous T-Cell Lymphomas: A Study of the Spanish Working Group of Cutaneous Lymphomas. / [Artículo traducido] Experiencia con bexaroteno en linfoma cutáneo de células T: un estudio del Grupo Español de Linfomas Cutáneos (GELC).

BACKGROUND AND OBJECTIVES: Bexarotene has been approved to treat advanced stage cutaneous T-cell lymphomas (CTCL) since 1999. However, very few data have been published on its long-term safety and efficacy profile. The aim of this study is to determine the tolerability to bexarotene and outcomes by collecting the 2nd largest case series to date on its long-term use vs CTCL. MATERIAL AND METHOD: This was a multicenter retrospective review of 216 patients with mycosis fungoides (174), or Sézary syndrome (42) on a 10-year course of bexarotene alone or in combination with other therapies at 19 tertiary referral teaching hospitals. RESULTS: A total of 133 men (62%) and 83 women (38%) were included, with a mean age of 63.5 year (27-95). A total of 45% were on bexarotene monotherapy for the entire study period, 22% started on bexarotene but eventually received an additional therapy, 13% were on another treatment but eventually received bexarotene while the remaining 20% received a combination therapy since the beginning. The median course of treatment was 20.78 months (1-114); and the overall response rate, 70.3%. Complete and partial response rates were achieved in 26% and 45% of the patients, respectively. Treatment was well tolerated, being the most common toxicities hypertriglyceridemia (79%), hypercholesterolemia (71%), and hypothyroidism (52%). No treatment-related grade 5 adverse events were reported. CONCLUSIONS: Our study confirms bexarotene is a safe and effective therapy for the long-term treatment of CTCL.

A meta-analysis evaluating effects of the rotigotine in Parkinson's disease, focusing on sleep disturbances and activities of daily living.

BACKGROUND: Rotigotine transdermal patch (TP) is a useful dopaminergic medication for Parkinson's disease (PD). This meta-analysis attempted to evaluate the effects of rotigotine TP on motor performance, activities of daily living (ADL) limitations, and sleep disturbances in patients with PD. METHODS: Only randomized controlled clinical trials (RCTs) with placebo design were included in this study. The clinical outcomes, evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS III), UPDRS-II, UPDRS Part II + III, Parkinson's Disease Sleep Scale (PDSS)-2, and adverse events (AEs) were evaluated. The Jadad scale was used to evaluate study quality. RESULTS: A total of 16 RCTs with 4682 patients with PD were enrolled in this study. We found that rotigotine TP significantly reduced the UPDRS-III, UPDRS-II, and UPDRS Part II + III scores, indicating that rotigotine TP led to a significant amelioration of movement symptoms and ADL limitations. Moreover, we found that rotigotine TP significantly reduced PDSS-2 scores, suggesting that rotigotine TP led to a remarkable improvement in sleep quality. Meanwhile, compared with the placebo group, patients taking rotigotine TP did not have added incidence of AEs. CONCLUSION: This study verified the efficacy and safety of rotigotine TP in treating PD. The findings of the present study provide compelling evidence concerning and insight into clinical usage of rotigotine TP. Future studies will focus on more non-motor symptoms affected by rotigotine TP.

Rotigotine patch prescription in inpatients with Parkinson's disease: evaluating prescription accuracy, delirium and end-of-life use.

BACKGROUND: Rotigotine patch, a trans-dermal dopamine agonist, is used acutely to replace oral dopaminergic medications for inpatients with Parkinson's disease where enteral routes are no longer available, and is also an option in end-of-life care where patients can no longer swallow. Concerns regarding acute use of Rotigotine include difficulty achieving dopaminergic equivalence, promotion of delirium/hallucinations and promotion of terminal agitation. OBJECTIVE: our objectives were to establish: (i) accuracy of Rotigotine prescribing, (ii) rates of delirium/hallucinations and (iii) rates of terminal agitation. METHOD: we retrospectively evaluated the use of Rotigotine in an inpatient population at a UK teaching hospital. Prescriptions between January 2018 and July 2019 were identified and inpatient records were analysed. OPTIMAL Calculator 2 was used as a gold standard for assessing conversion of oral dopaminergic medication to Rotigotine. RESULTS: a total of 84 inpatients were included. 25 (30%) patients were prescribed the recommended dose of Rotigotine; 31 (37%) higher and 28 (33%) lower than recommended. A total of 15 of 41 (37%) patients with dementia and 22 of 49 (45%) patients with delirium before initiation of Rotigotine inappropriately received the higher dose; 20 (24%) patients developed new/worsening delirium and 8 (10%) patients developed new/worsening hallucinations; and 59 (70%) patients were dead at time of evaluation, of these 40 (68%) died in hospital, 10 (25%) of whom experienced terminal agitation. CONCLUSIONS: acute conversion of oral dopaminergic medication to trans-dermal Rotigotine patch remains problematic despite the availability of validated tools. Inappropriate dosing may precipitate or worsen delirium/hallucinations. Use at end-of-life requires further evaluation.

Effects of dezocine and ropivacaine infiltration anesthesia on cellular immune function indicators, anesthesia recovery time and pain factors in patients with open liver resection.

The current experiment was carried out to explore the effects of dezocine combined with ropivacaine infiltration anesthesia on the anesthesia recovery time and pain factors of patients with open hepatectomy. A prospective randomized controlled method was used to select 92 patients with open liver cancer resection in our hospital from August 2017 to November 2019. The patients were divided into a study group (n=46) and a control group (n=46) using a computer-generated random number table. Both groups underwent general anesthesia, based on this, the study group was treated with ropivacaine infiltration anesthesia 10 minutes before skin incision, and dezocine was given intravenously 0.5 h before surgery, the control group was anesthetized with ropivacaine 10 minutes before the incision, and was given a saline injection 0.5 h before the operation. Compared the recovery of anesthesia (recovery time of spontaneous breathing, time to open eyes, time to extubation), the incidence of adverse reactions, and cellular immune function indicators (peripheral blood CD4+, CD4+/CD8+, NK cell levels), stress response indicators [serum blood glucose (Glu), norepinephrine (NE), adrenaline (E)], pain factors [serum dopamine (DA), neuropeptide Y (NPY), substance P (SP)] before induction of anesthesia (T0), completion of surgery (T1), 12 hours after surgery (T2), and 24 hours after surgery (T3) between the two groups, and the degree of pain (VAS score) at T2 and T3 were compared between the two groups. The levels of CD4+, CD4+/CD8+, and NK cells in peripheral blood at T1, T2, and T3 in the study group were higher than those in the control group (P<0.05); serum Glu, NE, and E levels in the study group at T1, T2, and T3 were lower than those in the control group (P<0.05); serum DA, NPY, and SP levels in the study group at T1, T2, and T3 were lower than those in the control group (P<0.05); the VAS scores of the study group at T2 and T3 were lower than those of the control group (P<0.05); the time of spontaneous breathing recovery, eyes opening and extubation in the study group were shorter than those in the control group (P<0.05); the incidence of restlessness (4.35%), transient hypertension (6.52%), and cough (2.17%) in the study group were lower than those in the control group (P<0.05). Dezocine and ropivacaine infiltration anesthesia can significantly shorten the recovery time of anesthesia and inhibit pain factor secretion in patients with open hepatectomy and can reduce the body's stress response after surgery, reduce immune function fluctuations, and can reduce the incidence of adverse reactions to anesthesia, and help promote patients' postoperative recovery.

Dezocine prevents sufentanil-induced cough during general anesthesia induction: a meta-analysis of randomised controlled trials.

BACKGROUND: Sufentanil is one of the opioids currently used to induce general anesthesia, and cough is one of the most common complications. Many drugs have been used to prevent sufentanil-induced cough (SIC), and dezocine is one of them. Dezocine is an analgesic, acting as partial antagonist of κ-receptors and agonist of µ-receptors. The purpose of our meta-analysis is to evaluate the efficacy of dezocine on SIC. METHODS: We searched multiple databases including PubMed, Embase, ScienceDirect, the Cochrane Library, and China National Knowledge Infrastructure databases (CNKI) to identify studies that met the inclusion criteria. This meta-analysis focused on the incidence and severity of SIC after dezocine intervention, as well as adverse effects. This meta-analysis was registered on PROSPERO with reference number ID: CRD 42020144943. RESULTS: Five randomised controlled trials (RCTs) were identified, including 890 patients. Each study was a comparison of dezocine with an equal volume of 0.9% saline. When the injection dose of dezocine was 0.1 mg/kg, the incidence (pooled risk ratio (RR) = 0.03, [95% CI: 0.02 to 0.07], P < 0.00001, I2 = 0%) and severity (mild: RR = 0.07, [95% CI: 0.03 to 0.18], P < 0.00001, I2 = 0%; moderate: RR = 0.05, [95% CI: 0.02 to 0.16], P < 0.00001, I2 = 0%; severe: RR = 0.04, [95% CI: 0.01 to 0.16], P < 0.00001, I2 = 0%) of SIC were significantly decreased. There were no statistically significant differences in vital signs between the two groups based on the results of the pooled analysis. CONCLUSION: This meta-analysis showed that dezocine significantly reduced the incidence and severity of SIC in the induction of general anesthesia, but had no significant effect on vital signs. More high-quality RCTs are needed to complement existing conclusions.

Synthetic Retinoid AM80 Ameliorates Lung and Arthritic Autoimmune Responses by Inhibiting T Follicular Helper and Th17 Cell Responses.

Rheumatoid arthritis is an autoimmune disorder that affects the joints and other organs. Pulmonary complications contribute significantly to rheumatoid arthritis mortality. Retinoic acid and its synthetic compound AM80 play roles in immunoregulation but their effect on mucosal autoimmunity remains largely unknown. T follicular helper (Tfh) and Th17 cells are known to promote inflammation and autoantibody production. Using the K/BxN autoimmune arthritis model, we elucidate a novel mechanism whereby oral AM80 administration suppressed lung mucosa-associated Tfh and autoantibody responses by increasing the gut-homing α4ß7 integrin expression on Tfh cells. This diverted Tfh cells from systemic (non-gut) inflamed sites such as the lung into the gut-associated lymphoid tissues, Peyer's patches, and thus reduced the systemic autoantibodies. AM80 also inhibited the lung Th17 response. AM80's effect in the lungs was readily applied to the joints as AM80 also inhibited Tfh and Th17 responses in the spleen, the major autoantibody producing site known to correlate with K/BxN arthritis severity. Finally, we used anti-ß7 treatment as an alternative approach, demonstrating that manipulating T cell migration between the gut and systemic sites alters the systemic disease outcome. The ß7 blockade prevented both Tfh and Th17 cells from entering the non-immunopathogenic site, the gut, and retained these T effector cells in the systemic sites, leading to augmented arthritis. These data suggest a dual beneficial effect of AM80, targeting both Tfh and Th17 cells, and warrant strict safety monitoring of gut-homing perturbing agents used in treating intestinal inflammation.

An observational study of rotigotine transdermal patch and other currently prescribed therapies in patients with Parkinson's disease.

Real-world data from large cohorts of patients with Parkinson's disease on the long-term effectiveness of different dopamine-substituting drug therapies are rare. The objective of this study was to obtain information on real-world management of PD with dopamine-substituting drugs. SP0854 (NCT00599339) was a prospective, multicenter, non-interventional, multiple-cohort, post-authorization safety study of rotigotine versus other dopaminergic therapies. The study was also part of a European Medicines Agency risk-management plan for the non-ergoline dopamine agonist rotigotine, focussing on cardiovalvular fibrosis. Eligible patients requiring monotherapy with a dopamine agonist, or levodopa in combination with a dopamine agonist were followed for ≤ 33 months; 1531 of 2195 patients completed the study. Mean motor scores improved for all dopamine-substituting treatments. Patients with more severe motor-symptoms/increased disability were more likely to receive levodopa alone or in combination with a DA at study onset. More patients who started on combination therapy with levodopa remained on this treatment versus those starting on dopaminergic monotherapy. This real-world study showed that the dopamine-substituting therapies were efficacious, with a safety profile consistent with that expected of dopaminergic treatments. Cardiovalvular pathology was rare and not found to be causally-related to rotigotine.

Hiccups in Parkinson's disease: an analysis of cases reported in the European pharmacovigilance database and a review of the literature.

BACKGROUND: Some reports have suggested an association between dopamine agonists and hiccups, involuntary contractions that merit full clinical attention because they can be very debilitating. Many drugs frequently used to treat hiccups are formally contraindicated in Parkinson's disease due to their liability to worsen motor symptoms, making the treatment of hiccups problematic in this disease. The objective of the present study was to analyze all spontaneous reports of hiccups from the European Pharmacovigilance Database in patients with Parkinson's disease and/or on dopaminergic drugs. Finally, we sought to identify evidence-based recommendations on the management of hiccups in Parkinson's disease. METHODS: We searched for all reports of hiccups in the European Pharmacovigilance Database (EudraVigilance) and calculated proportional reporting ratios for dopamine agonists and hiccups. We reviewed the literature on Parkinson's disease, dopamine agonists, and hiccups, searching for specific treatment recommendations for hiccups in this disease. RESULTS: Both rotigotine and pramipexole fulfilled the criteria to generate a safety signal. We found 32 and 13 cases of hiccups associated with dopamine agonists in EudraVigilance and the literature, respectively. There were no specific recommendations for the management of hiccups in Parkinson's disease in the clinical guidelines consulted. CONCLUSIONS: We have found evidence that rotigotine and pramipexole are associated with the appearance of hiccups and that this adverse reaction occurs predominantly in males. Given the scarce information available, specific recommendations are needed in clinical guidelines for the adequate management of hiccups in Parkinson's disease.

Safety and Efficacy of Rotigotine for Treating Parkinson's Disease: A Meta-Analysis of Randomised Controlled Trials.

We aimed to comprehensively analyse the safety and efficiency of rotigotine for treating Parkinson's disease (PD). We conducted systematic literature searches of Cochrane library, PubMed and Embase databases up to April 2016, with 'Rotigotine', 'Parkinson Disease ' and 'Parkinson's disease' as key searching terms. Outcomes, including Unified Parkinson's Disease Rating Scale (UPDRS) Part III and Part II scores, 'off' time, adverse events (AEs), serious AEs and discontinuation because of AEs, were compared between rotigotine and placebo groups under a fixed or random effect model. For dichotomous and continuous data, risk ratio (RR) and weighted mean difference with their corresponding 95% confidence intervals (95% CIs) were taken as the effect sizes to calculate merged results. Twelve eligible studies were included. For patients with early or advanced PD, rotigotine could significantly improve UPDRS Part III and Part II scores (p < 0.001) and it had significantly higher incidence of AEs than the placebo (p < 0.001). Regarding discontinuation because of AEs, rotigotine showed a significant advantage over placebo in patients with early PD, whereas the overall result demonstrated no statistically significant difference between the groups. Rotigotine can improve daily living and motor ability of patients with PD, although it has higher incidence of AEs. Rotigotine might be more appropriate for patients with advanced PD than for those with early PD. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Omega-3 fatty acids as adjunctive treatment for bexarotene-induced hypertriglyceridaemia in patients with cutaneous T-cell lymphoma.

BACKGROUND: Bexarotene is an oral retinoid approved for treating cutaneous T-cell lymphoma (CTCL) in patients resistant to first-line systemic treatment. Hypertriglyceridaemia is an unavoidable adverse effect of bexarotene therapy, and requires monitoring because of the risk of developing pancreatitis. Therefore, prophylactic hypolipidaemic therapy, usually with a fibrate alone, is required for preventing bexarotene-induced hypertriglyceridaemia. Despite these measures, a large number of patients develop very severe hypertriglyceridaemia. AIM: To assess the lipid metabolism changes before and after the use of a combination of omega-3 fatty acids (n-3 FA) plus fenofibrate compared with fenofibrate alone as a more effective lipid-lowering therapy in patients with CTCL treated with bexarotene. METHODS: From January 2005 to January 2013, we analysed all 25 patients with CTCL treated with bexarotene. The first 18 consecutively enrolled patients received fenofibrate alone as a lipid-lowering therapy, and the next 7 consecutively enrolled patients received a combination of fenofibrate and n-3 FA. RESULTS: Data for all 25 consecutive patients with CTCL treated with bexarotene were evaluated. Of these, 24 patients (96%) developed hypertriglyceridaemia despite the hypolipidaemic therapy, with this being very severe (> 11.2 mmol/L) in 20% of the cases. Of the 18 patients receiving fenofibrate alone, 5 (28%) developed very severe hypertriglyceridaemia, compared with none of the 7 patients treated with the n-3 FA combination. CONCLUSIONS: Our results suggest that the n-3 FA combination may be more effective than fibrate alone for preventing bexarotene-induced hypertriglyceridaemia.

Risk factors for postoperative delirium after spine surgery in middle- and old-aged patients.

BACKGROUND: Postoperative delirium is a common complication following various operative procedures with an incidence rate of 10-77 %. AIM: To analyze various risk factors for postoperative delirium after spine surgery in the middle- and old-aged patients. METHODS: This study retrospectively reviewed 451 patients (226 males and 225 females, an average age of 65.1 ± 18.3 years) who underwent spinal surgery in our hospital between January 2010 and August 2015. Patients who had features of acute onset and fluctuating course and any two of the other features were diagnosed with delirium. Cognitive tests consisting of Clinical Dementia Rating and Global Deterioration Scale were performed to evaluate delirium. T tests were used for statistical analysis of the difference between the two groups, and logistic regression analyses were used for determining the risk factors. RESULTS: A total of 42 (9.3 %) patients were diagnosed with delirium. Delirious and non-delirious patients had no difference in age, gender, BMI, education level, drug treatment, comorbid disease history, surgical history, preoperative blood pressure, intraoperative blood loss, blood transfusion, use of surgical implants, surgical site, use of fentanyl and propofol, and preoperative VAS score. Intraoperative hypotension and use of dezocine were related to postoperative delirium (P = 0.03 and P = 0.07). The multiple regression equation was Y = -0.11 + 0.52 × X 0 + 0.21 × X 1, where X 0 = amount of dezocine, X 1 = instances of intraoperative hypotension. CONCLUSION: Postoperative delirium commonly occurs after spine surgery. Intraoperative hypotension <80 mmHg and intraoperative use of dezocine represent valuable new predictors of the risk of delirium.

Eosinophilic Dermatosis of Hematologic Malignancy. / Dermatosis eosinofílicas asociadas a procesos hematológicos.

Dermatosis characterized by tissue eosinophilia arising in the context of hematologic disease is known as eosinophilic dermatosis of hematologic malignancy. The most commonly associated malignancy is chronic lymphocytic leukemia. Eosinophilic dermatosis of hematologic malignancy is a rare condition with a wide variety of clinical presentations, ranging from papules, erythematous nodules, or blisters that simulate arthropod bites, to the formation of true plaques of differing sizes. Histology reveals the presence of abundant eosinophils. We present 4 new cases seen in Hospital Arnau de Vilanova, Valencia, during the past 7 years. Three of these cases were associated with chronic lymphocytic leukemia and 1 with mycosis fungoides. It is important to recognize this dermatosis as it can indicate progression of the underlying disease, as was the case in 3 of our patients.

Research on dezocine in peritoneal gynecology operation under the target organ effect.

This paper was aimed to further analyze the concrete clinical efficacy of dezocine as an anesthetic for peritoneal gynecology operation and to offer a scientific guidance for future surgical treatments. This paper randomly selected 1000 peritoneal gynecology operation patients in 5 hospitals from January to December 2015 as research objects in the observation group, who were mainly applied with dezocine in operative anesthesia. By analyzing data of cases, it concluded efficacy characteristics of dezocine in various phases, and thus provide scientific guidance for future surgical treatments. Another 500 patients who were given with fentanyl as anesthetic in peritoneal gynecology operation were selected as research objects in the control group. We compared the two groups in aspects of index changes before and after operative anesthesia, VAS scores and haemodynamics changes in 2 hours of anesthesia. The results showed that, index changes occurred in both of groups after anesthesia, but patients in the observation group presented a more obvious efficacy with a significant difference (P<0.05). Besides, adverse reactions in both of groups during the operation were basically comparative, so there was no significant difference (P>0.05) or statistical value. This research demonstrated that dezocine, as an anaesthetic in gynecology operation, has a good therapeutic effect and value of wide application in clinical anesthesia.

Impulse control disorder related behaviours during long-term rotigotine treatment: a post hoc analysis.

BACKGROUND AND PURPOSE: Dopamine agonists in Parkinson's disease (PD) are associated with impulse control disorders (ICDs) and other compulsive behaviours (together called ICD behaviours). The frequency of ICD behaviours reported as adverse events (AEs) in long-term studies of rotigotine transdermal patch in PD was evaluated. METHODS: This was a post hoc analysis of six open-label extension studies up to 6 years in duration. Analyses included patients treated with rotigotine for at least 6 months and administered the modified Minnesota Impulse Disorders Interview. ICD behaviours reported as AEs were identified and categorized. RESULTS: For 786 patients, the mean (±SD) exposure to rotigotine was 49.4 ± 17.6 months. 71 (9.0%) patients reported 106 ICD AEs cumulatively. Occurrence was similar across categories: 2.5% patients reported 'compulsive sexual behaviour', 2.3% 'buying disorder', 2.0% 'compulsive gambling', 1.7% 'compulsive eating' and 1.7% 'punding behaviour'. Examining at 6-month intervals, the incidence was relatively low during the first 30 months; it was higher over the next 30 months, peaking in the 54-60-month period. No ICD AEs were serious, and 97% were mild or moderate in intensity. Study discontinuation occurred in seven (9.9%) patients with ICD AEs; these then resolved in five patients. Dose reduction occurred for 23 AEs, with the majority (73.9%) resolving. CONCLUSIONS: In this analysis of >750 patients with PD treated with rotigotine, the frequency of ICD behaviour AEs was 9.0%, with a specific incidence timeline observed. Active surveillance as duration of treatment increases may help early identification and management; once ICD behaviours are present rotigotine dose reduction may be considered.

Polish Lymphoma Research Group Experience With Bexarotene in the Treatment of Cutaneous T-Cell Lymphoma.

Bexarotene, a synthetic retinoid licensed for the treatment of refractory cutaneous T-cell lymphoma (CTCL), has been used clinically in Poland since 2007 in 21 patients. The objective of our retrospective, multicenter study was to evaluate our experience with bexarotene therapy, including efficacy, safety, and survival outcomes. We retrospectively identified 21 adult patients who were treated with bexarotene between the years 2007 and 2012. Starting dose of bexarotene was 300 mg/m per day. The analysis included 3 patients with early-stage mycosis fungoides (MF), 16 patients with advanced-stage MF, and 2 patients with Sézary syndrome (SS). The mean duration of therapy with bexarotene was 14.5 months. Use of bexarotene resulted in an overall response rate of 81.0%, although the overall mortality rate was 52.8%. In our study, early-stage CTCL responded better than advanced-stage CTCL (100.0% vs. 77.8%, respectively). The mean time to observable response was 1.8 months, and the mean duration of the response was 16.4 months. Most significant side effects were hyperlipidemia, hypothyroidism, and a bleeding gastric ulcer. Based on the results of our analysis, bexarotene is a valuable tool in the treatment of refractory early-stage CTCL. Although a majority of patients initially responded to therapy, the high mortality rate in the advanced-stage group suggests that bexarotene does not completely resolve the therapeutic problems in all stages of CTCL. Patient stratification for bexarotene treatment may need a thorough reassessment, in that bexarotene may not be an effective drug in the very advanced stages of CTCL.

[Endocrine complications of modern cancer therapy]. / Endokrinní komplikace moderní onkologické lécby.

Treatment with tyrosine kinase inhibitors leads to thyroid dysfunction in up to one half of treated patients, hypothyroidism being the most common. It is caused by destructive thyroiditis, impaired transport of T4 into the cell and deiodinase induction. Bexarotene is a nuclear retinoid X receptor agonist. Its application is accompanied with central hypothyroidism and hypertriglyceriaemia in virtually all patients and it also increases thyroxin metabolism. Autoimmune endocrine side effects are common in cancer immunotherapy. Cytokines (interpheron α and interleukin 2) cause autoimmune thyroiditis in 2-10 % of treated patients. Therapy with immune checkpoints inhibitors is connected with a variety of immune-related adverse events (irAE). Endocrine irAE include hypophysitis and thyroiditis during treatment with monoclonal antibodies against CTLA4 and thyroid dysfunction during therapy with antibody against CD1 receptor and its ligand. Knowledge, early recognition and management of these side effects is crucial.Key words: bexarotene - endocrine complication - hypophysitis - immune checkpoint inhibitors - immunotherapy.