Classification of anticancer drugs: an update with FDA- and EMA-approved drugs.

Anticancer systemic therapy comprises a complex and growing group of drugs. Some of the new agents with novel mechanisms of action that have appeared are difficult to fit in the groups of classical chemotherapy, hormones, tyrosine-kinase inhibitors, and monoclonal antibodies. We propose a classification based on two levels of information: the site of action and the mechanism of action. Regarding the former, drugs can exert their action in the tumor cell, the tumor vasculature, the immune system, or the endocrine system. The mechanism of action refers to the molecular target.

Fear of Recurrence in Advanced Cancer Patients: Sociodemographic, Clinical, and Psychological Correlates.

Fear of cancer recurrence significantly impacts advanced cancer patients, prompting emotional distress and increased healthcare utilization. This present study aims to analyze the fear of recurrence among patients with advanced cancer undergoing systemic treatment and its relationship with sociodemographic, clinical, and psychological factors. A multicenter cross-sectional study was conducted in 15 oncology departments across Spain, involving patients with locally advanced, unresectable, or metastatic cancer eligible for systemic treatment. Participants provided demographic information and completed instruments such as the Cancer Worry Scale, Brief Symptom Inventory, Mishel Uncertainty in Illness Scale, and the Duke-UNC-11 Functional Social Support Questionnaire (DUFSSQ). A total of 1195 participants participated: median age 66, 56% male, mostly metastatic cancers (80%), and common tumor sites. Two fear groups emerged: 28% low and 72% high levels of fear. High fear was associated with being female, being younger, lower levels of education, and worse survival estimates. High fear correlated with more depression, anxiety, somatic symptoms, uncertainty, and stronger social support. Multivariate analyses indicated that younger patients, those with shorter survival estimates, higher depression and anxiety scores, more uncertainty, and stronger social support had a greater likelihood of experiencing fear of recurrence, while the opposite was true for older patients. This study underscores distinct fear of recurrence profiles in advanced cancer patients, emphasizing the need for targeted interventions and support. Future research should delve deeper into understanding their repercussions for improving patient care and well-being.

Dignity and psychosocial related variables in elderly advanced cancer patients.

INTRODUCTION: Most cancers occur in older individuals, who are more vulnerable due to functional impairment, multiple comorbidities, cognitive impairment, and lack of socio-familial support. These can undermine patients' sense of dignity. This study seeks to compare dignity scores in older patients with advanced cancer on sociodemographic and clinical variables and analyze the predictive value of anxiety, depression, functional limitations, and social support on dignity scores. METHODS: A prospective, multicenter, observational study conducted with participation of 15 hospitals in Spain from February 2020 to October 2021. Patients with newly-diagnosed, advanced cancer completed the dignity (PPDS), anxiety and depression (BSI), Social Support (Duke-UNC-11), and functional limitations (EORTC-C30) scales. Lineal regression analyses explored the effects of anxiety, depression, functional status, and social support on dignity, adjusting for sociodemographic and clinical variables. RESULTS: A total of 180 subjects participated in this study. The results of the correlation analysis revealed that dignity correlated negatively with anxiety, depression, and sex, and positively with social support, functional status, and longer estimated survival. Thus, women, and more anxious and depressed individuals scored lower on the dignity scale, whereas patients with more social support, fewer functional limitations, and longer estimated survival scored higher. CONCLUSION: In conclusion, being female, having a lower educational level, lower estimated survival, depression, anxiety, less social support, and limited functionality are correlated with less dignity in the elderly with advanced cancer. It is a priority to manage both physical and psychological symptoms in patients with unresectable advanced cancer to mitigate psychological distress and increase their sense of dignity.

Understanding the immune response and the current landscape of immunotherapy in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumor with high lethality. Even with surgery, radiotherapy, chemotherapy, and other locoregional or systemic therapies, the survival rates for PDAC are low and have not significantly changed in the past decades. The special characteristics of the PDAC's microenvironment and its complex immune escape mechanism need to be considered when designing novel therapeutic approaches in this disease. PDAC is characterized by chronic inflammation with a high rate of tumor-associated macrophages and myeloid-derived suppressor cells and a low rate of natural killer and effector T cells. The pancreatic microenvironment is a fibrotic, microvascularized stroma that isolates the tumor from systemic vascularization. Immunotherapy, a novel approach that has demonstrated effectiveness in certain solid tumors, has failed to show any practice-changing results in pancreatic cancer, with the exception of PDACs with mismatch repair deficiency and high tumor mutational burden, which show prolonged survival rates with immunotherapy. Currently, numerous clinical trials are attempting to assess the efficacy of immunotherapeutic strategies in PDAC, including immune checkpoint inhibitors, cancer vaccines, and adoptive cell transfer, alone or in combination with other immunotherapeutic agents, chemoradiotherapy, and other targeted therapies. A deep understanding of the immune response will help in the development of new therapeutic strategies leading to improved clinical outcomes for patients with PDAC.

What do we know about cancer immunotherapy? Long-term survival and immune-related adverse events

Immunotherapy delivered a new therapeutic option to the oncologist: Ipilimumab (anti-CTLA-4), Nivolumab and Pembrolizumab (anti-PD1), and Atezolizumab (anti-PD-L1) increase overall survival and show a better safety profile compared to chemotherapy in patients with metastatic melanoma, lung, renal cancer among others. But all that glitters is not gold and there is an increasing number of reports of adverse effects while using immune-checkpoint inhibitors. While chemotherapy could weaken the immune system, this novel immunotherapy could hyper-activate it, resulting in a unique and distinct spectrum of adverse events, called immune-related adverse events (IRAEs). IRAEs, ranging from mild to potentially life-threatening events, can involve many systems, and their management is radically different from that of cytotoxic drugs: immunosuppressive treatments, such as corticoids, infliximab or mycophenolate mofetil, usually result in complete reversibility, but failing to do so can lead to severe toxicity or even death. Patient selection is an indirect way to reduce adverse events minimizing the number of subjects exposed to this drugs: unfortunately PDL-1, the actual predictive biomarker, would not allow clinicians select or exclude patients for treatment with checkpoint inhibitors

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What do we know about cancer immunotherapy? Long-term survival and immune-related adverse events.

Immunotherapy delivered a new therapeutic option to the oncologist: Ipilimumab (anti-CTLA-4), Nivolumab and Pembrolizumab (anti-PD1), and Atezolizumab (anti-PD-L1) increase overall survival and show a better safety profile compared to chemotherapy in patients with metastatic melanoma, lung, renal cancer among others. But all that glitters is not gold and there is an increasing number of reports of adverse effects while using immune-checkpoint inhibitors. While chemotherapy could weaken the immune system, this novel immunotherapy could hyper-activate it, resulting in a unique and distinct spectrum of adverse events, called immune-related adverse events (IRAEs). IRAEs, ranging from mild to potentially life-threatening events, can involve many systems, and their management is radically different from that of cytotoxic drugs: immunosuppressive treatments, such as corticoids, infliximab or mycophenolate mofetil, usually result in complete reversibility, but failing to do so can lead to severe toxicity or even death. Patient selection is an indirect way to reduce adverse events minimizing the number of subjects exposed to this drugs: unfortunately PDL-1, the actual predictive biomarker, would not allow clinicians select or exclude patients for treatment with checkpoint inhibitors.

Safety and Efficacy of PD-1 Inhibitors Among HIV-Positive Patients With Non-Small Cell Lung Cancer.

INTRODUCTION: Despite widespread administration of programmed death receptor 1 (PD-1) pathway inhibitors among individuals with NSCLC, little is known about the safety and activity of these agents among human immunodeficiency virus (HIV) - infected patients since this population has largely been excluded from immunotherapy clinical trials. METHODS: Here, we describe seven patients with metastatic NSCLC and HIV infection who were treated with PD-1 inhibitors nivolumab (two cases) or pembrolizumab (five cases with three in the first-line setting). RESULTS: Partial responses to immune checkpoint inhibitors were observed in three of seven cases. Among four patients with a programmed death ligand-1 tumor proportion score ≥50%, three partial responses were observed. All patients received antiretroviral therapy while on anti-PD-1 treatment. None of the patients experienced grade 3 or 4 immune-related adverse events or immune reconstitution inflammatory syndrome, and none required PD-1 inhibitor dose interruption or discontinuation due to toxicity. CONCLUSIONS: Nivolumab and pembrolizumab can be safe and effective among patients with NSCLC and HIV. Larger studies will be needed to determine the overall safety and efficacy of immune checkpoint inhibitors among cancer patients with HIV.