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Experimental Dermatology Oct 2014Cetuximab and panitumumab are epidermal growth factor receptor (EGFR) inhibitors used in metastatic colorectal cancer (mCRC). Most patients develop a papulopustular rash...
Cetuximab and panitumumab are epidermal growth factor receptor (EGFR) inhibitors used in metastatic colorectal cancer (mCRC). Most patients develop a papulopustular rash that may predict tumor response to treatment. EGFR gene polymorphisms may also determine tumor response and appearance of skin rash. We hypothesized an association between EGFR gene polymorphisms, papulopustular rash and response to anticancer treatment. Four EGFR polymorphisms (-216, -191, CA-SSR, R521K) were analysed in 51 patients with mCRC receiving anti-EGFR. Severity of cutaneous rash and tumor response was measured following standard scales. We report an association between SNP-216 and tumor response (P = 0.003): no tumor progression occurred in TT genotype. Moreover, 92.3% of the responder patients developed skin rash, 62.9% of them presenting a grade ≥2 (P = 0.015). Thus, although underpowered, our preliminary data suggest that SNP-216 polymorphism of the EGFR gene could be useful in predicting tumor response and the appearance of severe skin rash might also be associated.
Topics: Aged; Antibodies, Monoclonal; Antineoplastic Agents; Cetuximab; Colorectal Neoplasms; ErbB Receptors; Exanthema; Female; Genes, erbB-1; Humans; Male; Microsatellite Repeats; Middle Aged; Models, Genetic; Panitumumab; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Treatment Outcome
PubMed: 25039761
DOI: 10.1111/exd.12510 -
Current Opinion in Oncology Jul 2011As the number and uses for targeted therapies such as epidermal growth factor receptor inhibitors (EGFRIs) increase, so does the need to recognize and treat the... (Review)
Review
PURPOSE OF REVIEW
As the number and uses for targeted therapies such as epidermal growth factor receptor inhibitors (EGFRIs) increase, so does the need to recognize and treat the dermatologic side-effects of these agents. Although agents such as gefitinib, erlotinib, cetuximab, lapatinib, and panitumumab have less systemic side-effects than traditional cytotoxic chemotherapy, dermatologic adverse events from EGFRIs are significantly more common. These dermatologic toxicities have previously led to reduction or cessation of therapy and recently have been shown to decrease patients' quality of life.
RECENT FINDINGS
This review provides a symptom-based treatment approach to the common dermatologic adverse effects seen with the epidermal growth factor receptor antagonists: papulopustular rash, xerosis, pruritus as well as hair, nail, and mucosal changes. Each dermatologic toxicity is described; prophylaxis and treatment options, from topical to systemic, are presented based on a review of the current literature with emphasis on new clinical trials results. We also provide specific recommendations based on our practice in a specialty clinic.
SUMMARY
Although the field continues to evolve, this review presents the most up-to-date information on managing dermatologic adverse effects of EGFRIs. Practitioners should find this article to be a practical resource in approaching patients on EGFRIs with dermatologic toxicities. As we learn how to optimally manage the adverse effects of these agents, we practitioners have the opportunity to increase patients' quality of life and decrease reductions or cessations of life-prolonging therapy.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Cetuximab; Drug Eruptions; ErbB Receptors; Erlotinib Hydrochloride; Gefitinib; Humans; Lapatinib; Molecular Targeted Therapy; Panitumumab; Protein Kinase Inhibitors; Quinazolines
PubMed: 21537180
DOI: 10.1097/CCO.0b013e3283474063 -
Zhonghua Yu Fang Yi Xue Za Zhi [Chinese... Jan 2022The epidermal growth factor receptor (EGFR) signaling is aberrantly overexpressed in many solid malignancies, making it an important target for anti-cancer biologic... (Review)
Review
The epidermal growth factor receptor (EGFR) signaling is aberrantly overexpressed in many solid malignancies, making it an important target for anti-cancer biologic agents. Among them, epidermal growth factor receptor inhibitors (EGFRIs), which have been widely used in clinical practice, include anti-EGFR monoclonal antibodies and tyrosine kinase inhibitors. A proportion of patients treated with EGFRIs develop specific, dose-dependent skin toxicity such as papulopustular rash, paronychia, xerosis and itch. These side effects can cause physical and psychosocial discomfort that may result in dose reduction, discontinuance, or replacement of the current EGFRIs treatment. Correct diagnosis and treatment of these skin and mucosal adverse effects associated with EGFRIs is of great significance for the tertiary prevention of malignant tumors. A review on EGFRI-related mucocutaneous adverse reactions is presented here, focusing on the pathogenesis, the various clinical manifestations, the strategies for prevention and treatment of these conditions.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; ErbB Receptors; Humans; Neoplasms; Protein Kinase Inhibitors
PubMed: 35092997
DOI: 10.3760/cma.j.cn112150-20210601-00528 -
Cutaneous and Ocular Toxicology Sep 2017Cetuximab is an epidermal growth factor receptor inhibitor. It is frequently used in the treatment of solid tumors. However, it has a high potential to cause acne-like...
CONTEXT
Cetuximab is an epidermal growth factor receptor inhibitor. It is frequently used in the treatment of solid tumors. However, it has a high potential to cause acne-like rash. Demodex mites, which are known to increase in number in immunosuppressive circumstances, are closely related to the acneiform lesions.
OBJECTIVE
The aim of this study is to evaluate the presence of demodex mites in acne-like rash that appears under the treatment of Cetuximab.
METHODS
We reviewed the medical records of patients who applied to our clinic with cetuximab induced papulopustular rashes between November 2014 and March 2016. Demodex sampling was performed by standardized skin surface biopsy (SSSB) in a total of 11 patients (eight males and three females). Infestation was defined as at least 5 living parasites/cm of skin.
RESULTS
Upon the SSSB examination in 10 out of the 11 patients, no demodex mites were detected. Demodex mites were found in only one of the patients. This patient, in whom two dead Demodex folliculorums were found through facial sampling, was also regarded as negative since his demodex density was under the threshold limit value.
CONCLUSION
In this study, it has been concluded that acne-like rash that develops under the treatment of cetuximab is not related to the presence of demodex mites. Papulopustular eruptions that develop under cetuximab treatment should not be directly correlated with the presence of demodex; first SSSB and demodex presence should be evaluated.
Topics: Adult; Aged; Animals; Antineoplastic Agents, Immunological; Cetuximab; Drug Eruptions; ErbB Receptors; Female; Humans; Male; Middle Aged; Mite Infestations; Mites; Protein Kinase Inhibitors
PubMed: 27802779
DOI: 10.1080/15569527.2016.1253095 -
Clinical Drug Investigation Sep 2019The use of targeted therapies, when added to conventional chemotherapy, has significantly improved clinical outcomes and survival of cancer patients. While targeted... (Review)
Review
The use of targeted therapies, when added to conventional chemotherapy, has significantly improved clinical outcomes and survival of cancer patients. While targeted therapies do not have the systemic adverse reactions of chemotherapy, they are associated with toxicities that can be severe and impair patient quality of life and adherence to anti-cancer treatment. Panitumumab and cetuximab, two monoclonal antibodies against epidermal growth factor receptor (EGFR), are recommended for the treatment of metastatic colorectal cancer (mCRC). The majority of patients with mCRC who are treated with anti-EGFR therapy develop skin toxicities, including papulopustular rash (the most common), xerosis, painful cracks and fissures on the palms and soles of the feet, paronychia, pruritus, and abnormal hair and eyelash growth; they are also more prone to skin infections. Given the involvement of EGFR in normal epidermis physiology, development and function, skin toxicities caused by anti-EGFR therapy are not unexpected. In recent years, recommendations have been formulated for the prevention and treatment of anti-EGFR therapy-related skin toxicities. Indeed, proper and timely management of these toxicities is important for ensuring uninterrupted anti-cancer treatment and optimal outcomes. Here, we review the current knowledge of anti-EGFR therapy-related skin toxicities and the latest recommendations for their management. We also present a treatment approach for papulopustular rash based on the combination of fusidic acid plus betamethasone in a lipid-enriched topical formulation. The effectiveness of this approach is documented by the presentation of five cases successfully treated in clinical practice for anti-EGFR therapy-related rash.
Topics: Antineoplastic Agents, Immunological; Cetuximab; Colorectal Neoplasms; ErbB Receptors; Exanthema; Humans; Neoplasm Metastasis; Panitumumab; Patient Compliance; Practice Guidelines as Topic; Quality of Life
PubMed: 31264159
DOI: 10.1007/s40261-019-00811-7 -
Der Hautarzt; Zeitschrift Fur... May 2013A 73-year-old man has been suffering from a pulmonary adenocarcinoma for three years. He has been treated with the EGF-inhibitor erlotinib for the past 18 months. While...
A 73-year-old man has been suffering from a pulmonary adenocarcinoma for three years. He has been treated with the EGF-inhibitor erlotinib for the past 18 months. While taking this medication he developed a progressive papulopustular rash on his face and trunk which later spread to his thighs. Topical treatment with methylprednisolone and nadifloxacin, as well as short courses of systemic doxycycline and ciprofloxacin, led to marked improvement and control of his skin condition.
Topics: Acneiform Eruptions; Adenocarcinoma; Aged; Anti-Bacterial Agents; Anti-Inflammatory Agents; Ciprofloxacin; Doxycycline; Drug Therapy, Combination; Erlotinib Hydrochloride; Fluoroquinolones; Humans; Lung Neoplasms; Male; Methylprednisolone; Quinazolines; Quinolizines; Treatment Outcome
PubMed: 23535946
DOI: 10.1007/s00105-013-2551-z -
Indian Journal of Dermatology,... 2022
Topics: Humans; Acute Generalized Exanthematous Pustulosis; Behcet Syndrome; Exanthema; Anti-Bacterial Agents
PubMed: 35962496
DOI: 10.25259/IJDVL_1044_2021 -
Advances in Wound Care Feb 2013Epidermal growth factor (EGF) and EGF receptor (EGFR) play an essential role in wound healing through stimulating epidermal and dermal regeneration. The development of... (Review)
Review
SIGNIFICANCE
Epidermal growth factor (EGF) and EGF receptor (EGFR) play an essential role in wound healing through stimulating epidermal and dermal regeneration. The development of new therapies for enhancing wound healing has included the use of EGF. In addition, EGFR inhibitors (EGFRis) have become a therapeutic option for the treatment of cancer. Thus, therapies targeting EGF/EGFR are useful for the treatment of both cutaneous wounds and cancer.
RECENT ADVANCES
Identification of EGFR as a regulator of normal and pathological cell function has allowed for the development of EGFRis for the treatment of cancer and topical administration of EGF to enhance wound healing.
CRITICAL ISSUES
The use of EGFRi has emerged as an option for metastatic cancers. These drugs induce dermatological toxicity, a papulopustular rash that is pruritic and painful; chronic use may negatively impact wound healing. Currently, there is no standard therapy to alleviate the side effects caused by EGFRi administration except to reduce or eliminate EGFRi usage. Therefore, side effects from these drugs should be taken into consideration on patients prone to develop chronic wounds and with cutaneous injuries.
FUTURE DIRECTIONS
There is a need for adjunctive treatment to eliminate dermatological toxicity from EGFRi use. The development of new downstream targets of EGFR may be a rational strategy to reduce potential cutaneous side effects and provide a better strategy for the treatment of cancer. Until then, the topical use of EGF could be used to ameliorate dermatological lesions caused by EGFRi.
PubMed: 24527320
DOI: 10.1089/wound.2011.0326 -
International Journal of Dermatology Dec 2022Cutaneous side effects are commonly seen in cancer chemotherapy. As new chemotherapy drugs are developed, the frequency and the diversity of these cutaneous side effects...
BACKGROUND
Cutaneous side effects are commonly seen in cancer chemotherapy. As new chemotherapy drugs are developed, the frequency and the diversity of these cutaneous side effects increase. For this reason, identification and management of these side effects are an important part of the treatment of cancer patients. This study aimed to investigate mucocutaneous side effects of conventional chemotherapy and targeted therapy agents that are used in cancer patients.
METHODS
In this cross-sectional study, 231 cancer patients, who received single or combination chemotherapy at the oncology department of our hospital between 2013 and 2020, were retrospectively reviewed, and mucocutaneous side effects we evaluated.
RESULTS
The ages of the patients varied between 27 and 90 years with a median age of 60 years. Of the patients, 136 (58.9%) were women, and 95 (41.1%) were men. Combination chemotherapy was applied to 174 patients (71.9%). A total of 558 mucocutaneous side effects were present in 231 patients. The most common side effect was alopecia, which was observed in 158 patients (65.6%). This was followed by mucositis (39.4%), hand-foot syndrome (35.3%), papulopustular rash (22%), dermatitis (18.3%), xerosis (14.1%), nail disorders (12%), and others.
CONCLUSIONS
Although chemotherapy-induced cutaneous side effects are not usually life-threatening, they may lead to the development of morbidity and discontinuance or termination of the treatment. Therefore, these side effects should be well managed to improve the quality of life of cancer patients.
Topics: Male; Humans; Female; Middle Aged; Adult; Aged; Aged, 80 and over; Retrospective Studies; Quality of Life; Cross-Sectional Studies; Antineoplastic Agents; Neoplasms
PubMed: 35867950
DOI: 10.1111/ijd.16361 -
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