scholarly journals French Endocrine Society Guidance on endocrine side effects of immunotherapy

2019 ◽  
Vol 26 (2) ◽  
pp. G1-G18 ◽  
Author(s):  
F Castinetti ◽  
F Albarel ◽  
F Archambeaud ◽  
J Bertherat ◽  
B Bouillet ◽  
...  
Keyword(s):  
Side Effects ◽  
Expert Opinion ◽  
Checkpoint Inhibitors ◽  
High Dose ◽  
Cancer Therapies ◽  
Endocrine Society ◽  
Consensus Document ◽  
Expert Opinions ◽  
Frequent Use ◽  
Fulminant Diabetes

The management of cancer patients has changed due to the considerably more frequent use of immune checkpoint inhibitors (ICPIs). However, the use of ICPI has a risk of side effects, particularly endocrine toxicity. Since the indications for ICPI are constantly expanding due to their efficacy, it is important that endocrinologists and oncologists know how to look for this type of toxicity and how to treat it when it arises. In view of this, the French Endocrine Society initiated the formulation of a consensus document on ICPI-related endocrine toxicity. In this paper, we will introduce data on the general pathophysiology of endocrine toxicity, and we will then outline expert opinion focusing primarily on methods for screening, management and monitoring for endocrine side effects in patients treated by ICPI. We will then look in turn at endocrinopathies that are induced by ICPI including dysthyroidism, hypophysitis, primary adrenal insufficiency and fulminant diabetes. In each chapter, expert opinion will be given on the diagnosis, management and monitoring for each complication. These expert opinions will also discuss the methodology for categorizing these side effects in oncology using ‘common terminology criteria for adverse events’ (CTCAE) and the difficulties in applying this to endocrine side effects in the case of these anti-cancer therapies. This is shown in particular by certain recommendations that are used for other side effects (high-dose corticosteroids, contraindicated in ICPI for example) and that cannot be considered as appropriate in the management of endocrine toxicity, as it usually does not require ICPI withdrawal or high-dose glucocorticoid intake.

scholarly journals Nephrotoxicity of Cancer Immunotherapies: Past, Present and Future

2018 ◽  
Vol 29 (8) ◽  
pp. 2039-2052 ◽  
Author(s):  
Mark A. Perazella ◽  
Anushree C. Shirali
Keyword(s):  
Clinical Practice ◽  
Immune System ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Hematologic Malignancies ◽  
High Dose ◽  
Cancer Therapies ◽  
Chemotherapeutic Drugs ◽  
The Past ◽  
Cancer Immunotherapies

Nephrotoxicity from cancer therapies is common and increasingly encountered in clinical practice, such that the subfield of “onco-nephrology” has emerged. Conventional chemotherapeutic drugs and novel agents targeting specific genes/proteins are effective cancer therapies but suffer from a number of adverse kidney effects. An effective avenue of cancer treatment is immunotherapy, which uses drugs that augment immune system–mediated recognition and targeting of tumor cells. As such, leveraging the immune system to target malignant cells represents an important modality in eradicating cancer. IFN and high-dose IL-2 are older immunotherapies used in clinical practice to treat various malignancies, whereas new cancer immunotherapies have emerged over the past decade that offer even more effective treatment options. The immune checkpoint inhibitors are an exciting addition to the cancer immunotherapy armamentarium. Chimeric antigen receptor T cells are also a new immunotherapy used to treat various hematologic malignancies. However, as with the conventional and targeted cancer agents, the immunotherapies are also associated with immune-related adverse effects, which includes nephrotoxicity.

scholarly journals Endocrine complications of new anticancer therapies

2021 ◽  
Vol 75 ◽  
pp. 191-198
Author(s):  
Michał Miner ◽  
Michał Elbaum ◽  
Aleksandra Jawiarczyk-Przybyłowska ◽  
Eliza Kubicka
Keyword(s):  
Side Effects ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Myelogenous Leukemia ◽  
Cytotoxic T Cell ◽  
Cancer Therapies ◽  
Programmed Death ◽  
New Cancer Therapies ◽  
Endocrine Complications

Studying and analyzing of complex molecular mechanisms and immunological processes of cancer enables oncology to introduce new cancer therapies. In the treatment of cancer, we successively increase the use of targeted therapies with tyrosine kinase inhibitors and mTOR inhibitors and immunotherapy using checkpoint inhibitors CTLA-4 (cytotoxic T-cell antigen-4) and PD-1/PD-L1 (programmed death receptor 1/programmed death ligand 1). New anticancer drugs gradually replace conventional chemotherapy and have already found application in the treatment of many cancers, including thyroid cancer, hepatocellular carcinoma, non-small cell lung cancer, kidney cancer, bladder cancer, melanoma, breast cancer, acute and chronic myelogenous leukemia. The use of these drugs is less toxic than classical chemotherapy, but it can cause gastrointestinal, cardiovascular, respiratory, skin and endocrine complications. Most of the side effects of new cancer therapies are mild and moderate disorders, however some might be severe and life-threatening. Endocrinopathies are one of the more common side effects of these treatments. They can affect many endocrine glands (pituitary, thyroid, parathyroid, adrenal, pancreas) and cause both transient and permanent disorders.

scholarly journals Transplant strategies in relapsed/refractory Hodgkin lymphoma

Blood ◽  
2018 ◽  
Vol 131 (15) ◽  
pp. 1689-1697 ◽  
Author(s):  
Gunjan L. Shah ◽  
Craig H. Moskowitz
Keyword(s):  
Side Effects ◽  
Hodgkin Lymphoma ◽  
Checkpoint Inhibitors ◽  
Remission Rate ◽  
Therapeutic Option ◽  
Response Rates ◽  
Hematopoietic Cell ◽  
High Dose ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant

Abstract The majority of patients with Hodgkin lymphoma (HL) are cured with initial therapy. However, high-dose therapy with autologous hematopoietic cell transplant (AHCT) allows for the cure of an additional portion of patients with relapsed or primary refractory disease. Positron emission tomography–negative complete remission before AHCT is critical for long-term disease control. Several salvage options are available with comparable response rates, and the choice can be dependent of comorbidities and logistics. Radiation therapy can also improve the remission rate and is an important therapeutic option for selected patients. Brentuximab vedotin (BV) maintenance after AHCT is beneficial in patients at high risk for relapse, especially those with more than 1 risk factor, but can have the possibility of significant side effects, primarily neuropathy. Newer agents with novel mechanisms of action are under investigation to improve response rates for patients with subsequent relapse, although are not curative alone. BV and the checkpoint inhibitors nivolumab and pembrolizumab are very effective with limited side effects and can bridge patients to curative allogeneic transplants (allo-HCT). Consideration for immune-mediated toxicities, timing of allogeneic hematopoietic cell transplant based on response, and the potential for increased graft-versus-host disease remain important. Overall, prospective investigations continue to improve outcomes and minimize toxicity for relapsed or primary refractory HL patients.

The adverse kidney effects of cancer immunotherapies

2018 ◽  
Vol 2 (2-3) ◽  
pp. 56-68 ◽  
Author(s):  
Danielle L Saly ◽  
Mark A Perazella
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Interleukin 2 ◽  
High Dose ◽  
Cancer Therapies ◽  
Drug Induced ◽  
Acute Kidney Disease ◽  
Cancer Immunotherapies

Cancer therapies are a common cause of acute and chronic kidney disease, which are increasingly being seen by nephrologists in clinical practice. Conventional chemotherapeutic drugs and novel targeted agents are effective cancer therapies but their use is complicated by nephrotoxicity. Cancer immunotherapies exploit various properties of immune cells to enhance immune-mediated tumor killing. Interferon and high-dose interleukin-2 are older immunotherapies first employed clinically in the 1980s and 1990s to treat a number of different cancers. While effective, these two therapies have well-known systemic toxicities, which include acute kidney disease. The emergence of the new cancer immunotherapies over the past decade brings more effective treatment options. The immune checkpoint inhibitors and chimeric antigen receptor T cells are exciting additions to the cancer treatment armamentarium. These agents effectively treat a several and a growing list of cancers that have otherwise failed other therapies. However, as with the conventional and targeted cancer agents, drug-induced acute and chronic kidney disease is an untoward effect of this group of drugs. We will undertake a case-based review: the newer immunotherapies followed by the older therapies, interferon and interleukin-2.

Diagnosis and Management of Checkpoint Inhibitor Side Effects in Patients with Bladder Cancer: the Urologist’s Perspective

2020 ◽  
Vol 6 (4) ◽  
pp. 425-433
Author(s):  
Neal Shore
Keyword(s):  
Bladder Cancer ◽  
Side Effects ◽  
Corticosteroid Therapy ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Early Recognition ◽  
Cytotoxic T Cell ◽  
High Dose ◽  
Cell Mediated Immunity ◽  
Multiple Cancer

From 2016 through the present day, we have witnessed extraordinarily rapid advances and regulatory approvals of immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway, which has significantly improved survival among patients with advanced and metastatic urothelial carcinoma (mUC). Although these agents usually are well tolerated, their unique mechanism of action may enhance cytotoxic T-cell mediated immunity, evoking unique side effects that differ from conventional chemotherapy or molecularly targeted agents. The most common immune-related adverse events (irAEs) are dermatitis, colitis, pneumonitis, thyroid dysfunction, and transaminitis, but any organ system permeated by the lymphatic vasculature can be affected; also, neuropathies and arthralgias may occur. Immune-mediated events of any grade require prompt recognition and appropriate management to mitigate the risk of irAE exacerbation. Most patients with mild (grade 1) irAEs may continue checkpoint inhibitor treatment with careful monitoring. For grade 2 irAEs, it is appropriate to suspend treatment, initiate corticosteroid therapy, and only resume treatment if the irAE resolves to < grade 1. Events classified as > grade 3 may require permanent treatment cessation and high-dose corticosteroid therapy. In clinical trials of PD-1/PD-L1 inhibitors across multiple cancer types, approximately 15% of patients with mUC developed irAEs requiring corticosteroid therapy. Training physicians and nurse providers and counseling patients regarding the early recognition of irAEs are mandatory to ensure timely irAE detection and optimized patient management. Hence, operationalizing an advanced bladder cancer clinic requires collaboration and coordination amongst urologists, medical and radiation oncologists, and other medical specialists who participate in the increasingly multimodal and multidisciplinary care of patients with bladder cancer.

Nanoparticle-based Drug Delivery Systems for Targeted Epigenetics Cancer Therapy

2020 ◽  
Vol 21 (11) ◽  
pp. 1084-1098
Author(s):  
Fengqian Chen ◽  
Yunzhen Shi ◽  
Jinming Zhang ◽  
Qi Liu
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Cancer Therapy ◽  
Drug Delivery Systems ◽  
Therapeutic Index ◽  
Delivery Systems ◽  
Epigenetic Therapy ◽  
Cancer Therapies ◽  
Therapeutic Benefits ◽  
High Therapeutic Index

This review summarizes the epigenetic mechanisms of deoxyribonucleic acid (DNA) methylation, histone modifications in cancer and the epigenetic modifications in cancer therapy. Due to their undesired side effects, the use of epigenetic drugs as chemo-drugs in cancer therapies is limited. The drug delivery system opens a door for minimizing these side effects and achieving greater therapeutic benefits. The limitations of current epigenetic therapies in clinical cancer treatment and the advantages of using drug delivery systems for epigenetic agents are also discussed. Combining drug delivery systems with epigenetic therapy is a promising approach to reaching a high therapeutic index and minimizing the side effects.

Quality-by-Design Enabled Chitosan Nanoparticles for Antitubercular Therapy: Formulation, Statistical Optimization, and In vitro Characterization

2020 ◽  
Vol 15 ◽  
Author(s):  
Manasi M. Chogale ◽  
Sujay S. Gaikwad ◽  
Savita P. Kulkarni ◽  
Vandana B. Patravale
Keyword(s):  
Side Effects ◽  
Treatment Regimen ◽  
Research Work ◽  
Chitosan Nanoparticles ◽  
In Vitro Release ◽  
Antitubercular Therapy ◽  
Prolonged Treatment ◽  
High Dose ◽  
Average Size

Background: Tuberculosis (TB) continues to be among the leading causes for high mortality among developing countries. Though a seemingly effective treatment regimen against TB is in place, there has been no significant improvement in the therapeutic rates. This is primarily owing to the high drug doses, their associated sideeffects, and prolonged treatment regimen. Discontinuation of therapy due to the severe side effects of the drugs results in the progression of the infection to the more severe drug-resistant TB. Objectives: Reformulation of the current existing anti TB drugs into more efficient dosage forms could be an ideal way out. Nanoformulations have been known to mitigate the side effects of toxic, high-dose drugs. Hence, the current research work involves the formulation of Isoniazid (INH; a first-line anti TB molecule) loaded chitosan nanoparticles for pulmonary administration. Methods: INH loaded chitosan nanoparticles were prepared by ionic gelation method using an anionic crosslinker. Drugexcipient compatibility was evaluated using DSC and FT-IR. The formulation was optimized on the principles of Qualityby-Design using a full factorial design. Results: The obtained nanoparticles were spherical in shape having an average size of 620±10.97 nm and zeta potential +16.87±0.79 mV. Solid state characterization revealed partial encapsulation and amorphization of INH into the nanoparticulate system. In vitro release study confirmed an extended release of INH from the system. In vitro cell line based safety and efficacy studies revealed satisfactory results. Conclusion: The developed nanosystem is thus an efficient approach for antitubercular therapy.

Cutaneous Adverse Events of Immune Checkpoint Inhibitors: A Summarized Overview

2019 ◽  
Vol 14 (1) ◽  
pp. 14-20 ◽  
Author(s):  
Kerasia-Maria Plachouri ◽  
Eleftheria Vryzaki ◽  
Sophia Georgiou
Keyword(s):  
Side Effects ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Skin Toxicity ◽  
Maculopapular Rash ◽  
Symptomatic Treatment ◽  
Stevens Johnson Syndrome ◽  
Life Threatening ◽  
Skin Side Effects

Background:The introduction of Immune Checkpoint Inhibitors in the recent years has resulted in high response rates and extended survival in patients with metastatic/advanced malignancies. Their mechanism of action is the indirect activation of cytotoxic T-cells through the blockade of inhibitory receptors of immunomodulatory pathways, such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1) and its ligand (PD-L1). Despite their impressive therapeutic results, they can also induce immune-related toxicity, affecting various organs, including the skin.Objective:To provide an updated summarized overview of the most common immune-mediated cutaneous side effects and their management.Method:English articles derived from the databases PubMed and SCOPUS and published between 2009 and 2018, were analyzed for this narrative review.Results:The most common adverse cutaneous reactions include maculopapular rash, lichenoid reactions, vitiligo and pruritus, with severity Grade 1 or 2. Less frequent but eventually life-threatening skin side effects, including Stevens-Johnson syndrome, Drug Reaction with Eosinophilia and Systemic Symptoms and Toxic Epidermal necrolysis, have also been reported.Conclusion:Basic knowledge of the Immune-Checkpoint-Inhibitors-induced skin toxicity is necessary in order to recognize these treatment-related complications. The most frequent skin side effects, such as maculopapular rash, vitiligo and pruritus, tend to subside under symptomatic treatment so that permanent discontinuation of therapy is not commonly necessary. In the case of life-threatening side effects, apart from the necessary symptomatic treatment, the immunotherapy should be permanently stopped. Information concerning the management of ICIs-mediated skin toxicity can be obtained from the literature as well as from the Summary of Product Characteristics of each agent.

scholarly journals TNF-Alpha Inhibitors for Chronic Urticaria: Experience in 20 Patients

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Freja Lærke Sand ◽  
Simon Francis Thomsen
Keyword(s):  
Side Effects ◽  
Chronic Urticaria ◽  
Treatment Options ◽  
Significant Proportion ◽  
Response Duration ◽  
Immunosuppressive Drugs ◽  
Tnf Alpha ◽  
High Dose ◽  
Duration Of Treatment ◽  
Durable Response

Patients with severe chronic urticaria may not respond to antihistamines, and other systemic treatment options may either be ineffective or associated with unacceptable side effects. We present data on efficacy and safety of adalimumab and etanercept in 20 adult patients with chronic urticaria. Twelve (60%) patients obtained complete or almost complete resolution of urticaria after onset of therapy with either adalimumab or etanercept. Further three patients (15%) experienced partial response. Duration of treatment ranged between 2 and 39 months. Those responding completely or almost completely had a durable response with a mean of 11 months. Six patients (30%) experienced side effects and five patients had mild recurrent upper respiratory infections, whereas one patient experienced severe CNS toxicity that could be related to treatment with TNF-alpha inhibitor. Adalimumab and etanercept may be effective and relatively safe treatment options in a significant proportion of patients with chronic urticaria who do not respond sufficiently to high-dose antihistamines or in whom standard immunosuppressive drugs are ineffective or associated with unacceptable side effects.

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