Review of the Clinical Pharmacokinetics, Efficacy and Safety of Pembrolizumab.

BACKGROUND: Treatment of various types of cancer has been improved significantly with the discovery of biological drugs that act as immune checkpoint inhibitors (ICIs). Pembrolizumab is a humanized monoclonal anti- PD-1 antibody currently approved for the treatment of a wide range of tumors, with more indications still being investigated in ongoing clinical trials. OBJECTIVE: The aim of this paper is to present all currently available data regarding pembrolizumab pharmacokinetic and pharmacodynamic characteristics. Also, the possibility of using predictive biomarkers to monitor patients during cancer treatment is discussed. METHODS: Database research was carried out (PubMed, ScienceDirect). Information was gathered from original articles, the European Medicines Agency datasheets and results from clinical trials. RESULTS: This review summarizes present-day knowledge about the pharmacokinetics, different modeling approaches and dosage regimens, efficacy and safety of pembrolizumab and therapeutic monitoring of disease progression. CONCLUSION: This review points out consistent pharmacokinetic characteristics of pembrolizumab in various cancer patients, the lack of pharmacokinetic-pharmacodynamic/outcome relationships, and the need for adequate biomarkers to predict treatment success. Hence, there is a clear necessity for more data and experience in order to optimize pembrolizumab treatment for each individual patient.

Prevalence of burnout among healthcare professionals at the Serbian National Cancer Center.

OBJECTIVE: The aim of this study was to investigate the level of burnout and identify who is at highest risk among healthcare professionals (HCPs) working at the largest referent national institution. METHODS: A cross-sectional survey was conducted at the Institute of Oncology and Radiology of Serbia from May 2019 to July 2019, evaluating the level of burnout, depression, fatigue, socio-demographic, behavioral and professional characteristics, and quality of life among healthcare professionals. Of the 576 distributed questionnaires among physicians, nurses/technicians and healthcare coworkers, 432 participants returned their questionnaires (75%). All instruments used in our study had been validated and cross-culturally adapted to Serbian language. RESULTS: The overall prevalence of burnout was 42.4%, with the greatest proportion of burned out in emotional exhaustion domain (66.9%). The multivariable-adjusted model analysis showed that nurses/technicians had a 1.41 times greater chance of experiencing burnout, compared to physicians (OR = 1.41, 95% CI 1.16-7.10), and that with each year of work experience, the chance of burnout increased by about 2% (OR = 1.02, 95% CI 1.00-1.92). Furthermore, it was shown that, with each point in the PHQ-9 score for depression, probability of burnout increased by 14% (OR = 1.14, 95% CI 1.07-1.94). Finally, after controlling all these potential confounders, the Mental Composite Score of SF-36 score showed an independent prognostic value in exploring the burnout presence among HCPs (OR = 1.17, 95% CI 1.03-2.47). CONCLUSION: Our research showed a significant level of burnout among healthcare professionals working in oncology, especially among nurses/technicians. The development of effective interventions at both individual and organizational level toward specific risk groups is needed.

Hyperthermic intrathoracic chemotherapy (HITHOC) in ovarian carcinoma - a propos of a case.

A female patient aged 42, started chemotherapy for advanced ovarian carcinoma in June 2016. Considering intraoperative findings, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) were performed, followed by adjuvant chemotherapy. In March 2018, computed tomography (CT) examination showed disease progression in the form of pleural carcinomatosis with increased levels of tumor markers. In April 2018, total parietal pleurectomy, partial visceral pleurectomy, and then hyperthermic intrathoracic chemotherapy (HITHOC) with cisplatin were performed. The procedure was uneventful, as was the postoperative course. The patient was discharged on the 13th postoperative day with no major postoperative complications. Three months after surgery, CT showed no signs of disease relapse. Since this is a relatively new method of treating pleural carcinomatosis, real results are to be expected with larger series of patients and longer postoperative follow-up.

Factors related to local recurrence of non small cell lung cancer and its operability.

PURPOSE: To analyze the correlation of primary tumor (PT) pathological characteristics (size, stage, type and grade) and the extent of initial surgical treatment of non small cell lung cancer (NSCLC) with the incidence and time to local recurrence (LR) and disease-free survival (DFS), as well as to determine in what way these parameters and LR localizations affect the possibility for surgical retreatment. METHODS: The research was conducted on 114 patients with NSCLC and LR that had initial surgery in two reference institutes in Serbia from January 2002 to December 2010. PT size and disease stage were defined according to the revised 2004 WHO classification. PTs were grouped by size into 3 categories. Due to great diversity, surgical procedures were sorted into 6 operation types. Standard statistical methods and tests were used for data analysis. RESULTS: Statistical analyses showed significant difference in DFS and LR reoperability that were related to PT size, disease stage and the extent of initial surgery. LR localization on the chest wall was favorable for secondary surgery due to LR. CONCLUSIONS: Squamous cell lung carcinoma relapses locally more frequently than other lung tumor types, and the commonest LR site is the chest wall. This localization provides high possibility for surgical retreatment. Adequate staging, proper indications for surgical treatment and quality surgery provide longer DFS in patients with NSCLC. All these suggest that the surgeon may be considered as the most significant factor of prognosis.

Correlation of tumor size as independent factor and disease stage with local recurrence of non-small cell lung carcinoma and its operability.

PURPOSE: To analyze the correlation of non-small cell lung carcinoma (NSCLC) primary tumor size, independently, and the initial disease stage with the incidence of local recurrence (LR) and disease-free survival (DFS), as well as the LR operability. METHODS: The research was conducted on 114 patients operated due to NSCLC at the Institute for Lung Diseases of the Clinical Center of Serbia and the Institute for Oncology and Radiology of Serbia from January 2002 to December 2010, who developed LR during the 5-year follow-up. Diagnostic methods and surgical approaches were standard, defined by protocols. Standard statistical methods and tests were used for data analysis. RESULTS: Statistical analysis showed significant difference in DFS and LR incidence in first 2 postoperative years related to primary tumor size and stage. Patients with T1 tumors (vs T2 vs T3), as well as in earlier disease stage, had significantly longer DFS. LR in the first and second year after primary tumor operation occurred more frequently with larger primary tumors. Significant correlation was registered between LR operability and primary tumor size, as well as LR operability and primary tumor stage. CONCLUSIONS: This research highlights size of the primary tumor as independent prognostic factor for patients with NSCLC. The likelihood of LR increases with larger primary tumor and higher primary tumor stages, while DFS decreases. Because larger tumors are more frequently understaged, with occult mediastinal metastases, their LR is not possible to be surgically treated.