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Journal of Clinical Medicine Jan 2021Epidermal Growth Factor Receptor inhibitors (EGFRi) are approved as therapeutic options in several solid tumors. Cutaneous papulopustular eruption is the most frequent...
Epidermal Growth Factor Receptor inhibitors (EGFRi) are approved as therapeutic options in several solid tumors. Cutaneous papulopustular eruption is the most frequent cutaneous adverse-event (AE), usually treated with emollient or corticosteroids according to toxicity grade. Our study evaluated the efficacy and safety of a topical product containing polydatin, a glycosylated polyphenol, natural precursor of resveratrol showing anti-inflammatory and anti-oxidative activities, for the prevention and treatment of skin papulopustular rash in EGFRi-treated patients. Forty oncologic patients treated with EGFRi were enrolled in two groups: group-A, 20 patients with papulopustular AE, and group-B, 20 patients without cutaneous manifestations. The study consisted of twice-daily application of polydatin cream 1.5% (group-A) and 0.8% (group-B) for 6 months. In group-A patients, we observed at week 4 a remarkable improvement of skin manifestation and quality of life evaluated with National-Cancer-Institute-Common-Terminology-Criteria for Adverse-Events (NCI-CTCAE), Dermatology-Life-Quality-Index (DLQI) score and Visual-Analogue-Scale (VAS) pruritus, with a statistical significance of < 0.05. None of the patients of group-B developed skin AEs to EGFRi. No cutaneous AEs related to the polydatin product were reported in both groups. Polydatin can be a good topical aid for the prevention and management of papulopustular rash in cancer patients receiving EGFRi, also capable of improving cancer patients' quality of life.
PubMed: 33530427
DOI: 10.3390/jcm10030466 -
Dermatology (Basel, Switzerland) 2021The incidence of epidermal growth factor receptor inhibitor (EGFRI)-induced papulopustular rash is 60-85%. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The incidence of epidermal growth factor receptor inhibitor (EGFRI)-induced papulopustular rash is 60-85%.
OBJECTIVE
To investigate prophylactic topical treatment for EGFRI-induced rash.
METHODS
A single-center, randomized, double-blind, placebo-controlled trial. Adult cancer patients initiating treatment with EGFRIs were randomized to receive facial topical treatment with chloramphenicol 3% + prednisolone 0.5% (CHL-PRED) ointment, chloramphenicol 3% (CHL) ointment, or aqua cream (AQUA). The primary end points were the incidence of ≥grade 3 rash using the Common Terminology Criteria for Adverse Events (CTCAE), on days 14 and 30. A subanalysis was conducted for incidence of a protocol-specified significant rash, defined as ≥10 facial papulopustular lesions.
RESULTS
The per-protocol analysis on day 14 included 69 patients, who received CHL-PRED (21), CHL (23), or AQUA (25). The incidence of CTCAE ≥grade 3 rash was not statistically significant between arms; however, the incidence of the protocol-specified significant rash was: CHL-PRED 14%, CHL 39%, and AQUA 48% (p = 0.03, CHL-PRED vs. AQUA). At 30 days, the CTCAE ≥grade 3 incidence was similar, but the incidences of protocol-specified significant rash were 6%, 16%, and 43% (p = 0.03, CHL-PRED vs. AQUA). No significant differences were found between CHL and CHL-PRED and between CHL and AQUA.
CONCLUSIONS
Prophylactic topical CHL-PRED was efficacious when compared to AQUA, in the treatment of EGFRI-induced facial papulopustular rash.
Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Inflammatory Agents; Chloramphenicol; Double-Blind Method; ErbB Receptors; Exanthema; Female; Humans; Male; Middle Aged; Neoplasms; Prednisolone; Protein Kinase Inhibitors
PubMed: 33378750
DOI: 10.1159/000511869 -
Oncoimmunology Nov 2020Anti-epidermal growth factor receptor (EGFR) monoclonal antibody is a standard treatment of metastatic colorectal cancer (mCRC) and its most common adverse effect is a...
Anti-epidermal growth factor receptor (EGFR) monoclonal antibody is a standard treatment of metastatic colorectal cancer (mCRC) and its most common adverse effect is a papulopustular acneiform rash. The aim of the CUTACETUX study was to characterize the skin inflammatory response associated with this rash and its relation to treatment efficacy. This prospective study included patients with mCRC treated with first-line chemotherapy plus cetuximab. Patients underwent skin biopsies before the initiation of cetuximab (D0) and before the third infusion (D28), one in a rash zone and one in an unaffected zone. Expression of Th17-related cytokines (IL-17A, IL-21, IL-22), antimicrobial peptides (S100A7 and BD-2), innate response-related cytokines (IL-1β, IL-6, TNF-α and OSM), T-reg-related cytokines (IL-10 and TGF-β), Th1-related cytokine (IFN-γ), Th2-related cytokine (IL-4), Thymic stromal lymphopoietin and keratinocyte-derived cytokines (IL-8, IL-23 and CCL20) were determined by RT-PCR. Twenty-seven patients were included. Levels of most of the cytokines increased at D28 in the rash zone compared to D0. No significant association was observed between variations of cytokines levels and treatment response in the rash zone and only the increase of IL-4 ( = .04) and IL-23 ( = .02) levels between D0 and D28 in the unaffected zone was significantly associated with treatment response. Increased levels of IL-8 ( = .02), BD-2 ( = .02), IL-1β ( = .004) and OSM ( = .02) in the rash zone were associated with longer progression-free survival. Expression of Th2-related and keratinocyte-derived cytokines in the skin was associated with anti-EGFR efficacy. If this inflammatory signature can explain the rash, the exact mechanism by which these cytokines are involved in anti-EGFR tumor response remains to be studied.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Colorectal Neoplasms; ErbB Receptors; Humans; Prospective Studies
PubMed: 33299659
DOI: 10.1080/2162402X.2020.1848058 -
The Journal of Dermatology Mar 2021Pediatric periorificial dermatitis is a papulopustular eruption found around the facial orifices in children. Although the treatment of the disease has been largely...
Pediatric periorificial dermatitis is a papulopustular eruption found around the facial orifices in children. Although the treatment of the disease has been largely anecdotal and experience-based, studies have shown that topical calcineurin inhibitors, as well as other topical and oral antibiotics, such as metronidazole, can be effective treatment options. However, most of the studies with a sizable number of patients have been based on the Caucasian population. Herein, we evaluated the clinical efficacy of topical calcineurin inhibitors and topical/oral metronidazole in 24 Korean patients with pediatric periorificial dermatitis. The majority of the patients showed a complete response to treatment.
Topics: Administration, Topical; Anti-Bacterial Agents; Calcineurin Inhibitors; Child; Dermatitis, Perioral; Exanthema; Humans; Metronidazole
PubMed: 33275294
DOI: 10.1111/1346-8138.15695 -
Cutaneous and Ocular Toxicology Dec 2020Epidermal growth factor receptor inhibitors (EGFRs) are chemotherapeutic agents used in multiple solid organ malignity. These medications have common dermatological side... (Clinical Trial)
Clinical Trial
INTRODUCTION
Epidermal growth factor receptor inhibitors (EGFRs) are chemotherapeutic agents used in multiple solid organ malignity. These medications have common dermatological side effects, particularly papulopustular (PPL) lesions. The management of the diagnosis and treatment processes for such side effects may facilitate the continuation of chemotherapy and enhance the patient's quality of life.
OBJECTIVE
The objective of this study is to report the cutaneous side effects of EGFR inhibitors and to share treatment methods for such side effects.
MATERIALS AND METHODS
In this prospective study, 59 patients using EGFR due to breast and colorectal carcinoma at the oncology unit of Haseki Training and Research Hospital were assessed. The patients for whom EGFR was initiated were examined at the beginning of the treatment at weeks 1 and 2, their demographic characteristics were recorded, and the patients who developed a skin rash were followed up from the onset of the lesion. The PPL side effects that developed in the patients and other dermatological findings were recorded. The PPL side effects were graded, and the treatment plans were reported. The study was conducted between February 2016 and February 2018 under the approval of the local ethical committee.
RESULTS
The mean age of the 59 patients (47 females, 12 males) taking EGFR inhibitors was 52.4 ± 12.0 (range: 29-84). Forty-five patients had early stage and 14 patients had advanced stage carcinoma. Fourteen patients had colorectal carcinoma, three patients had renal cancer, and 42 patients had breast cancer. Forty-two patients were using trastuzumab (single therapy in 29 patients and combined therapy in 13 patients), five patients were using cetuximab, three patients were using sunitinib, eight patients were using panitumumab, and six patients were using pertuzumab. In 22 patients, PPL side effects were observed in the skin; it was G1 in 19 patients and G2 in three patients. In seven patients who developed acneiform side effects, systemic doxycycline was used, and in others, topical tetracycline and clindamycin were used. Except for one patient using trastuzumab, all patients has lesions on the face, upper trunk, and back. One patient exhibited an atypical rash, which was diagnosed as a granulomatous follicular reaction. Xerosis was present in two cases, and paronychia, pyogenic granuloma, trichomegaly, and madarosis were observed in one patient each. The patients who developed an acneiform rash were treated with topical and systemic antibiotics, light keratolytics, and emollients. The skin side effects of all patients were mild to moderate, and all patients completed the chemotherapy process. An acneiform skin rash and other dermatological side effects are common with EGFR inhibitors. To treat these side effects, emollients, topical steroids, and local, systemic antibiotics are recommended. Clindamycin may be preferred as a topical treatment, and doxycycline may be preferred as a systematic treatment.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Breast Neoplasms; Colorectal Neoplasms; ErbB Receptors; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Prospective Studies; Protein Kinase Inhibitors; Skin Diseases
PubMed: 33028137
DOI: 10.1080/15569527.2020.1833028 -
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 -
Pediatric Dermatology Jul 2020
Topics: Drug Eruptions; Exanthema; Humans
PubMed: 32706466
DOI: 10.1111/pde.14164 -
Clinical Colorectal Cancer Dec 2020Medical treatment of advanced colorectal cancer is effective in prolonging the survival of patients. The aim of this study was to describe the most common skin...
INTRODUCTION
Medical treatment of advanced colorectal cancer is effective in prolonging the survival of patients. The aim of this study was to describe the most common skin toxicities that occur in those patients, analyzing the association between the type of reaction and the different chemotherapeutic drugs; and to evaluate the importance of an outpatient dermatologic service to improve quality of life.
PATIENTS AND METHODS
Seventy-two patients with skin reactions from advanced colorectal cancer chemotherapy were included. Each patient underwent physical examination and digital photographic imaging, and completed a quality-of-life questionnaire (Dermatology Life Quality Index [DLQI]).
RESULTS
Papulopustular rash was the most common side effect observed. It was statistically associated with EGFRi + irinotecan, EGFRi + FOLFOX, and EGFRi. Xerosis occurred in 50% of patients during EGFRi therapy. Periungual pyogenic granuloma-like lesions occurred in 30% of patients during EGFRi therapy. Our data underline a statistically significant association between capecitabine, FOLFOX + EGFRi, FOLFIFI + EGFRi, and hand-foot syndrome (P < .001). Because none of patients treated with EGFRi alone developed this kind of reaction, we suppose that it is associated with the use of 5-fluorouracil. Fifty percent of patients receiving anti-epidermal growth factor receptor (EGFR) therapy developed trichomegaly. These data underline a statistically significant association between these reactions and this specific drug.
CONCLUSION
A dermatologic visit is useful, both for the correct diagnosis of and for the adequate therapy of chemotherapy side effects. The prevention and treatment of these toxicities are important, not only to improve quality of life but also to avoid unnecessary dose reduction or interruption, which can have a negative effect on treatment outcome.
Topics: Administration, Cutaneous; Aged; Anti-Bacterial Agents; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Eruptions; Emollients; Female; Glucocorticoids; Histamine Antagonists; Humans; Incidence; Male; Middle Aged; Quality of Life; Severity of Illness Index; Surveys and Questionnaires
PubMed: 32665093
DOI: 10.1016/j.clcc.2020.05.006 -
Journal of Patient-reported Outcomes Jul 2020Papulopustular rash is a common class effect of epidermal growth factor receptor inhibitors (EGFRI) that can affect patients' health-related quality of life and cause...
A prospective study to validate the functional assessment of cancer therapy (FACT) for epidermal growth factor receptor inhibitor (EGFRI)-induced dermatologic toxicities FACT-EGFRI 18 questionnaire: SWOG S1013.
BACKGROUND
Papulopustular rash is a common class effect of epidermal growth factor receptor inhibitors (EGFRI) that can affect patients' health-related quality of life and cause disruptions to treatment. SWOG S1013 (NCT01416688) is a multi-center study designed to validate the Functional Assessment of Cancer Therapy EGFRI 18 (FACT-EGFRI 18) using 7-items from the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 to assess EGFRI-induced skin-related toxicities and their impact on functional status.
METHODS
Patients with a diagnosis of colorectal or lung cancer to receive EGFRI therapies for at least 6 weeks were enrolled. Patient self-assessments using the FACT-EGFRI 18 were completed prior to undergoing CTCAE assessment by trained clinicians at baseline, weekly × 6, and then monthly × 3. The psychometric properties of the FACT-EGFRI 14 (skin toxicity items only) and 18 (plus 2 nail and 2 hair items) were established based on criterion validity, known groups validity, internal consistency reliability, and responsiveness to change.
RESULTS
Of the 146 registered patients, 124 were evaluable. High Cronbach's alpha (> 0.70) for both FACT-EGFRI 14 and FACT-EGFRI 18 scores across assessment times were observed. Although agreement (i.e. criterion validity) between individual and summary scales of the FACT-EGFRI 18 for assessing skin toxicity was good, agreement with the clinician-reported CTCAE was only fair. The minimal important difference was determined to be 3 points. The results also demonstrated responsiveness to symptom change.
DISCUSSION
Based on the results of this multi-center validation study, the FACT-EGFRI 18 patient-reported outcome instrument provided data from the patient's perspective yielding unique information as well as complementing clinician-rated CTCAE grades, especially for the symptoms of pain, pruritus, and paronychia.
CONCLUSIONS
Good to excellent psychometric properties for the FACT-EGFRI 18 were demonstrated, supporting further use of this patient-reported outcomes measure. Additional validation with a more diverse group of patients should be conducted.
PubMed: 32642992
DOI: 10.1186/s41687-020-00220-x -
IDCases 2020We present a case of Disseminated Herpes Zoster in a 73 year old man who had been taking Glatiramer acetate for 8 years as treatment for Multiple Sclerosis. He...
We present a case of Disseminated Herpes Zoster in a 73 year old man who had been taking Glatiramer acetate for 8 years as treatment for Multiple Sclerosis. He presented to the emergency room with complaints of a painful skin lesions on his buttocks and was found to have a generalized papulo-pustular rash. He was treated with IV Acyclovir and concurrent Piperacillin-Tazobactam plus Vancomycin for disseminated herpes zoster with a necrotic bacterial superinfection on his buttocks. Multiple Sclerosis is a chronic immune mediated disease of the CNS and is treated with immunomodulators and immunosuppressive medications. With more than 2 decades of Glatiramer acetate use, it is regarded as the safest immunomodulator without any associated reported infections. This is the first case of Disseminated Herpes Zoster associated with Glatiramer.
PubMed: 32637319
DOI: 10.1016/j.idcr.2020.e00873