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Clinical Microbiology and Infection :... Jun 2018The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH)... (Review)
Review
ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Cell surface receptors and associated signaling pathways).
BACKGROUND
The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) consensus document on the safety of targeted and biologic therapies.
AIMS
To review, from an infectious diseases perspective, the safety profile of therapies targeting cell surface receptors and associated signaling pathways among cancer patients and to suggest preventive recommendations.
SOURCES
Computer-based Medline searches with MeSH terms pertaining to each agent or therapeutic family.
CONTENT
Vascular endothelial growth factor (VEGF)-targeted agents (bevacizumab and aflibercept) are associated with a meaningful increase in the risk of infection, likely due to drug-induced neutropaenia, although no clear benefit is expected from the universal use of anti-infective prophylaxis. VEGF tyrosine kinase inhibitors (i.e. sorafenib or sunitinib) do not seem to significantly affect host's susceptibility to infection, and universal anti-infective prophylaxis is not recommended either. Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab or panitumumab) induce neutropaenia and secondary skin and soft tissue infection in cases of severe papulopustular rash. Systemic antibiotics (doxycycline or minocycline) should be administered to prevent the latter complication, whereas no recommendation can be established on the benefit from antiviral, antifungal or anti-Pneumocystis prophylaxis. A lower risk of infection is reported for anti-ErbB2/HER2 monoclonal antibodies (trastuzumab and pertuzumab) and ErbB receptor tyrosine kinase inhibitors (including dual-EGFR/ErbB2 inhibitors such as lapatinib or neratinib) compared to conventional chemotherapy, presumably as a result of the decreased occurrence of drug-induced neutropaenia.
IMPLICATIONS
With the exception of VEGF-targeted agents, the overall risk of infection associated with the reviewed therapies seems to be low.
Topics: Antineoplastic Agents, Immunological; Biological Therapy; Clinical Trials as Topic; Communicable Disease Control; Communicable Diseases; Consensus; Enzyme Inhibitors; Humans; Immunocompromised Host; Molecular Targeted Therapy; Receptors, Cell Surface; Signal Transduction; Vascular Endothelial Growth Factor A
PubMed: 29426804
DOI: 10.1016/j.cmi.2017.12.027 -
Frontiers in Oncology 2022Zanubrutinib, a next-generation non-covalent Bruton's tyrosine kinase (BTK) inhibitor, shows great efficacy in the treatment of B cell malignancies. Some patients may...
Zanubrutinib, a next-generation non-covalent Bruton's tyrosine kinase (BTK) inhibitor, shows great efficacy in the treatment of B cell malignancies. Some patients may experience a series of side effects after the treatment of zanubrutinib. Grade 4 dermatological toxicities are rare, which present as severe rash and skin infection. Herein, we retrospectively reported the grade 4 dermatological toxicities of zanubrutinib in three consecutive patients. They were treated with zanubrutinib 160 mg twice daily orally. One patient was diagnosed with Primary Breast Diffuse Large B-cell Lymphoma(PB-DLBCL) and two patients were diagnosed with Chronic Lymphocytic Leukemia(CLL). Within one month after zanubrutinib treatment, all three patients developed grade 4 dermatological toxicities, including bruising, maculopapular rash, petechiae, ecchymosis, hemorrhagic blister, acne-Like rash, papulopustular rash, and skin infections. Zanubrutinib was discontinued in two patients due to unacceptable dermatological toxicities. Safety data from pre-licensing clinical trials showed that zanubrutinib-related side effects were frequent but well tolerated. To date, no severe dermatological toxicities were reported. The majority of patients can be relieved with symptomatic treatment, but a very small percentage of patients may face discontinuation of the drug.
PubMed: 35957865
DOI: 10.3389/fonc.2022.941633 -
Cancer Management and Research 2017Many publications describe preferences for colorectal cancer (CRC) screening; however, few studies elicited preferences for anticancer-drug treatment for metastatic CRC...
OBJECTIVE
Many publications describe preferences for colorectal cancer (CRC) screening; however, few studies elicited preferences for anticancer-drug treatment for metastatic CRC (mCRC). This study was designed to elicit preferences and risk tolerance among patients and oncologists in the USA for anticancer drugs to treat mCRC.
MATERIALS AND METHODS
Patients aged 18 years or older with a self-reported diagnosis of mCRC and board-certified (or equivalent) oncologists who had treated patients with mCRC were recruited by two survey research companies from existing online patient panels in the USA. Additional oncologists were recruited from a list of US physicians. Patients and oncologists completed a discrete-choice experiment (DCE) survey. DCEs offer a systematic method of eliciting preferences and quantifying both the relative importance of treatment attributes and the tradeoffs respondents are willing to make among benefits and risks. Treatment attributes in the DCE were progression-free survival (PFS) and risks of severe papulopustular rash, serious hemorrhage, cardiopulmonary arrest, and gastrointestinal perforation. Patients' and physicians' maximum levels of acceptable treatment-related risks for two prespecified increases in efficacy were estimated.
RESULTS
A total of 127 patients and 150 oncologists completed the survey. Relative preferences for the treatment attributes in the study were mostly consistent with the expectation that better clinical outcomes were preferred over worse clinical outcomes. Risk tolerance varied between patients and physicians. On average, physicians were willing to tolerate higher risks than patients, although these differences were mostly not statistically significant. Post hoc latent-class analyses revealed that some patients and physicians were unwilling to forgo any efficacy to avoid toxicities, while others were willing to make such tradeoffs.
CONCLUSION
Differences in preferences between patients and physicians suggest that there is the potential for improvement in patients' well-being. Initiating or enhancing discussions about patient tolerance for toxicities, such as skin rash and gastrointestinal perforations, may help prescribe treatments that entail more appropriate benefit-risk tradeoffs.
PubMed: 28490902
DOI: 10.2147/CMAR.S125245 -
Drugs in Context 2020Despite growing interest in cutaneous adverse events (CAEs) and their management in patients with cancer, they are often underreported and there are no extensive data on...
BACKGROUND
Despite growing interest in cutaneous adverse events (CAEs) and their management in patients with cancer, they are often underreported and there are no extensive data on their impact on quality of life (QoL). Healthcare professionals should consider this issue in order to minimize its negative impact on QoL and improve patient outcomes. This study evaluates the impact of CAEs on QoL in outpatients receiving anticancer drugs and aims to determine the differences in QoL between conventional chemotherapy targeted therapies.
METHODS
A total of 114 cancer patients with CAEs were included in this observational, cross-sectional study. Patient-reported outcomes instruments (Functional Assessment of Cancer Therapy - General, Dermatology Life Quality Index, and Skindex-16) were used.
RESULTS
Mean scores in QoL indices were 65.3±13.4, 8.4±5, and 30.8±16.9 in Functional Assessment of Cancer Therapy - General, Dermatology Life Quality Index, and Skindex-16, respectively. The CAEs that had the greatest impact on dermatologic-related QoL were hand-foot skin reaction, rash, palmo-plantar erythrodysesthesia, and papulopustular eruption. No significant differences in QoL indices according to the type of treatment (conventional chemotherapy targeted therapy) were observed.
CONCLUSIONS
CAEs, and particularly hand-foot toxicities, rashes, and papulopustular eruptions, can have an impact on QoL in outpatients receiving anticancer drugs as evaluated with three different patient-reported outcomes instruments. No differences in QoL related to CAEs were observed between conventional chemotherapy and targeted therapy.
PubMed: 32821263
DOI: 10.7573/dic.2020-6-6 -
Dermatology Reports Jun 2023Rapid and proper diagnosis of mucocutaneous presentations of COVID-19 which in many cases are representing internal organ damage is a key way to better approach these...
Mucocutaneous presentations of consultant critical and non-critical cases of admitted COVID-19 patients, outpatients, and vaccine-associated dermatoses: a clinical atlas and a large original study of two general COVID-19 centers from Iran.
Rapid and proper diagnosis of mucocutaneous presentations of COVID-19 which in many cases are representing internal organ damage is a key way to better approach these patients, and it could be even lifesaving. In this original study, we reported consultant critical and non-critical cases of admitted COVID-19 patients and some interesting outpatient cases for 14 months, and some newly encountered vaccine-associated dermatoses. We presented 121 cases divided into 12 categories; all had full multi-aspects photographs attached as an atlas to a . These categories were:1- Generalized papulopustular eruptions (3 patients), 2- Erythroderma (4 patients), 3- Maculopapular lesions(16 patients), 4- Mucosal lesions (8 patients), 5- Urticarial lesions and angioedema (16 patients), 6- Vascular injuries (22 patients), 7- Vesiculobullous lesions (12 patients), 8- The specific new onset of mucocutaneous presentations or aggravation of any especial previous dermatoses (9 patients), 9- Nail changes (3 patients), 10- Hair loss (2 patients), 11- Non-specific mucocutaneous problems (16 patients) and 12-Vaccine-associated dermatoses (10 patients).In the pandemic, if we countered with extensive mucocutaneous lesions with vascular components or vesiculobullous erosive lesions in association with any cutaneous rash that could be an alarming sign of a probable life-threatening systemic event, we would need to approach them as soon as possible.
PubMed: 37426367
DOI: 10.4081/dr.2023.9473 -
Actas Dermo-sifiliograficas 2015Cetuximab and panitumumab are monoclonal antibodies that target the epidermal growth factor receptor (EGFR) in the treatment of metastatic colorectal cancer. Most... (Observational Study)
Observational Study
INTRODUCTION AND OBJECTIVES
Cetuximab and panitumumab are monoclonal antibodies that target the epidermal growth factor receptor (EGFR) in the treatment of metastatic colorectal cancer. Most patients develop a papulopustular rash, which may predict tumor response. We studied whether the other adverse cutaneous effects associated with these monoclonal antibodies are also clinical predictors of response. We also reviewed publications describing approaches to treating the papulopustular rash since no evidence-based guidelines have yet been published.
MATERIAL AND METHODS
We performed a retrospective study of 116 patients with metastatic colorectal cancer receiving anti-EGRF therapy with cetuximab or panitumumab at Hospital Universitario Donostia.
RESULTS
In total, 81.9% of the patients developed a papulopustular rash. Patients who received the most cycles of treatment with the EGFR inhibitor were at the highest risk of developing the rash, and these patients also had the most severe rash reactions (P=.03). All of the patients who exhibited a complete tumor response had the rash, and the incidence of rash was lower in patients with poor tumor response (P=.03). We also observed an association between tumor response and xerosis (53.4% of the patients who developed xerosis also exhibited tumor response, P=.002). The papulopustular rash was managed according to an algorithm developed by our department.
CONCLUSIONS
Severe papulopustular rash and xerosis may be clinical predictors of good response to anti-EGFR therapy. Patients who develop a papulopustular rash should be treated promptly because suboptimal treatment of this and other adverse effects can lead to delays in taking the prescribed anti-EGFR dose or to interruption of therapy.
Topics: Adenocarcinoma; Aged; Algorithms; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antipruritics; Cetuximab; Colorectal Neoplasms; Dermatologic Agents; Drug Eruptions; Drug Therapy, Combination; ErbB Receptors; Female; Humans; Male; Middle Aged; Neoplasm Proteins; Panitumumab; Protein Kinase Inhibitors; Retrospective Studies; Skin Diseases, Papulosquamous; Treatment Outcome
PubMed: 25798804
DOI: 10.1016/j.ad.2015.01.006 -
Clinical Colorectal Cancer Jun 2018Monoclonal antibody inhibitors of the epidermal growth factor receptor (EGFR) have been shown to improve outcomes for patients with metastatic colorectal cancer (mCRC)...
Monoclonal antibody inhibitors of the epidermal growth factor receptor (EGFR) have been shown to improve outcomes for patients with metastatic colorectal cancer (mCRC) without RAS gene mutations. However, treatment with anti-EGFR agents can be associated with toxicities of the skin, nails, hair, and eyes. Because these dermatologic toxicities can result in treatment discontinuation and affect patient quality of life, their management is an important focus when administering anti-EGFR monoclonal antibodies. The present systematic review describes the current data reporting the nature and incidence of, and management and treatment options for, dermatologic toxicities occurring during anti-EGFR treatment of mCRC. A search of the National Library of Medicine PubMed database from January 1, 2009, to August 18, 2016, identified relevant reports discussing dermatologic toxicity management among patients with mCRC receiving anti-EGFR therapy. The studies were grouped by type and rated by level of evidence using the GRADE approach developed by the Agency for Healthcare Research and Quality. Overall, 269 reports were reviewed (nonrandomized trials, n = 120; randomized trials, n = 31; retrospective studies, n = 15; reviews, n = 39). Dermatologic toxicity of any grade occurs in most patients who receive anti-EGFR therapy; approximately 10% to 20% of patients experienced grade 3/4 toxicity. The most common dermatologic toxicities include papulopustular/acneiform rash, xerosis, and pruritus; however, nail changes, hair abnormalities, and ocular conditions also occur. Guidance for managing these toxicities includes the use of inexpensive emollient ointments and moisturizers, avoidance of sun exposure, avoidance of irritants, and the use of short showers. Several studies also found that preemptive treatment was more effective than reactive treatment at limiting the incidence and severity of skin toxicity. With appropriate treatment, the dermatologic toxicities associated with anti-EGFR monoclonal antibody therapy can be managed, minimizing patient discomfort and the need for therapy interruption and/or discontinuation. Additionally, preemptive treatment can reduce dermatologic toxicity severity, ultimately yielding better quality of life.
Topics: Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Cetuximab; Colorectal Neoplasms; Drug Eruptions; ErbB Receptors; Humans; Incidence; Panitumumab
PubMed: 29576427
DOI: 10.1016/j.clcc.2017.12.004 -
PloS One 2018Topical application of Vitamin K1 has been demonstrated to effectively treat papulopustular skin rash, a serious and frequently encountered side effect of Epidermal...
Topical application of Vitamin K1 has been demonstrated to effectively treat papulopustular skin rash, a serious and frequently encountered side effect of Epidermal Growth Factor Inhibitors (EGFRIs). Systemic absorption of vitamin K1 from skin and the resultant consequence of antagonizing EGFRIs anticancer effects jeopardizes the clinical acceptability of this rather effective treatment. The purpose of the present study was to rationally formulate and evaluate the release rate and transdermal absorption of a wide range of Vitamin K1 dermal preparations with a variety of physiochemical properties. A library of 33 formulations with were compounded and tested for Vitamin K1 permeation using hydrophobic membranes and porcine skin mounted in a Fran diffusion cells. Our results demonstrate the lowest diffusion for water-in-oil emulsions, which also demonstrated a negligible transdermal absorption. The statistical analysis showed a significant correlation between in vitro and ex vivo results. While viscosity did not have a significant impact on the diffusion or absorption of vitamin K1, an increase in the lipid content was correlated with an increase in transmembrane diffusion (not with transdermal absorption). Overall, formulation design significantly impacts the release rate and transdermal absorption of vitamin K1, and confirms the possibility of minimal systemic distribution of this vitamin for this specific purpose.
Topics: Administration, Topical; Animals; Antineoplastic Agents; Dermatologic Agents; Diffusion; Emulsions; Gels; In Vitro Techniques; Lipids; Membranes, Artificial; Ointments; Skin; Skin Absorption; Skin Cream; Skin Diseases; Surface-Active Agents; Sus scrofa; Viscosity; Vitamin K 1; Water
PubMed: 30289881
DOI: 10.1371/journal.pone.0204531 -
Actas Dermo-sifiliograficas 2015
Topics: Dermatologists; EGF Family of Proteins; Exanthema; Humans; Protein Kinase Inhibitors
PubMed: 26028577
DOI: 10.1016/j.ad.2015.05.001 -
BMJ Case Reports Aug 2018Cetuximab and osimertinib are epidermal growth factor receptors (EGFRs) inhibitors used in the treatment of several malignancies. These agents have been associated with...
Cetuximab and osimertinib are epidermal growth factor receptors (EGFRs) inhibitors used in the treatment of several malignancies. These agents have been associated with several skin lesions, the most common being papulopustular acneiform rash involving the face, neck, chest and back. Herein, we describe a unique toxic effect of these agents involving the fingertips and lateral aspects of fingers in a small patient series. The lesions presented approximately 4 weeks into treatment were cut-like and caused local discomfort/pain. Application of a colloidal solution allowed for partial resolution of these lesions in one patient, while discontinuation of the drug led to the disappearance of the lesions in another. Thus, we call for awareness of this unique skin toxicity with the use of EGFR inhibitors in patients with cancer.
Topics: Administration, Topical; Aged; Antineoplastic Agents; Cetuximab; Colloids; Colonic Neoplasms; Dermatologic Agents; Drug Eruptions; ErbB Receptors; Female; Fingers; Humans; Lung Neoplasms; Male; Middle Aged; Treatment Outcome
PubMed: 30068575
DOI: 10.1136/bcr-2017-224144