|
1
|
Felip E, Cho BC, Nguyen D, Curtin JC, Sethi S, Bauml JM, Lee SH. Reply to the Letter to the Editor regarding 'PFS, OS or toxicity: what is the most important factor in the treatment of EGFR-mutated lung cancer?' by T. Nishimura and H. Fujimoto. Ann Oncol 2025; 36:221-222. [PMID: 39521680 DOI: 10.1016/j.annonc.2024.10.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Accepted: 10/07/2024] [Indexed: 11/16/2024] Open
Affiliation(s)
- E Felip
- Medical Oncology Service, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Universitat Autonoma de Barcelona, Barcelona, Spain.
| | - B C Cho
- Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - D Nguyen
- City of Hope National Medical Center, Duarte, USA
| | - J C Curtin
- Janssen Research & Development, Spring House, USA
| | - S Sethi
- Janssen Research & Development, Spring House, USA
| | - J M Bauml
- Janssen Research & Development, Spring House, USA
| | - S-H Lee
- Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| |
Collapse
|
|
2
|
Chiusa M, Lee YA, Zhang MZ, Harris RC, Sherrill T, Lindner V, Brooks CR, Yu G, Fogo AB, Flynn CR, Zienkiewicz J, Hawiger J, Zent R, Pozzi A. Cytoplasmic retention of the DNA/RNA-binding protein FUS ameliorates organ fibrosis in mice. J Clin Invest 2024; 134:e175158. [PMID: 38488009 PMCID: PMC10940094 DOI: 10.1172/jci175158] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Accepted: 01/17/2024] [Indexed: 03/18/2024] Open
Abstract
Uncontrolled accumulation of extracellular matrix leads to tissue fibrosis and loss of organ function. We previously demonstrated in vitro that the DNA/RNA-binding protein fused in sarcoma (FUS) promotes fibrotic responses by translocating to the nucleus, where it initiates collagen gene transcription. However, it is still not known whether FUS is profibrotic in vivo and whether preventing its nuclear translocation might inhibit development of fibrosis following injury. We now demonstrate that levels of nuclear FUS are significantly increased in mouse models of kidney and liver fibrosis. To evaluate the direct role of FUS nuclear translocation in fibrosis, we used mice that carry a mutation in the FUS nuclear localization sequence (FUSR521G) and the cell-penetrating peptide CP-FUS-NLS that we previously showed inhibits FUS nuclear translocation in vitro. We provide evidence that FUSR521G mice or CP-FUS-NLS-treated mice showed reduced nuclear FUS and fibrosis following injury. Finally, differential gene expression analysis and immunohistochemistry of tissues from individuals with focal segmental glomerulosclerosis or nonalcoholic steatohepatitis revealed significant upregulation of FUS and/or collagen genes and FUS protein nuclear localization in diseased organs. These results demonstrate that injury-induced nuclear translocation of FUS contributes to fibrosis and highlight CP-FUS-NLS as a promising therapeutic option for organ fibrosis.
Collapse
Affiliation(s)
- Manuel Chiusa
- Department of Medicine, Division of Nephrology and Hypertension, and
| | - Youngmin A. Lee
- Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Ming-Zhi Zhang
- Department of Medicine, Division of Nephrology and Hypertension, and
| | - Raymond C. Harris
- Department of Medicine, Division of Nephrology and Hypertension, and
- Department of Veterans Affairs, Nashville, Tennessee, USA
| | - Taylor Sherrill
- Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Volkhard Lindner
- Center for Molecular Medicine, Maine Health Institute for Research, Scarborough, Maine, USA
| | - Craig R. Brooks
- Department of Medicine, Division of Nephrology and Hypertension, and
| | - Gang Yu
- Department of Neuroscience, Peter O’Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Agnes B. Fogo
- Department of Medicine, Division of Nephrology and Hypertension, and
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Charles R. Flynn
- Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Jozef Zienkiewicz
- Department of Veterans Affairs, Nashville, Tennessee, USA
- Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Jacek Hawiger
- Department of Veterans Affairs, Nashville, Tennessee, USA
- Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Roy Zent
- Department of Medicine, Division of Nephrology and Hypertension, and
- Department of Veterans Affairs, Nashville, Tennessee, USA
| | - Ambra Pozzi
- Department of Medicine, Division of Nephrology and Hypertension, and
- Department of Veterans Affairs, Nashville, Tennessee, USA
| |
Collapse
|
|
3
|
Spiro J, Wisniewski P, Schwartz J, Smith AG, Burger S, Tilley DH, Maves RC. Doxycycline Prophylaxis for Skin and Soft Tissue Infections in Naval Special Warfare Trainees, United States 1. Emerg Infect Dis 2024; 30:89-95. [PMID: 38146981 PMCID: PMC10756378 DOI: 10.3201/eid3001.230890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2023] Open
Abstract
In 2015, several severe cases of skin and soft tissue infection (SSTI) among US Naval Special Warfare trainees prompted the introduction of doxycycline prophylaxis during the highest-risk portion of training, Hell Week. We performed a retrospective analysis of the effect of this intervention on SSTI incidence and resulting hospital admissions during 2013-2020. In total, 3,371 trainees underwent Hell Week training during the study period; 284 SSTIs were diagnosed overall, 29 of which led to hospitalization. After doxycycline prophylaxis was introduced, admission rates for SSTI decreased from 1.37 to 0.64 admissions/100 trainees (p = 0.036). Overall SSTI rates remained stable at 7.42 to 8.86 SSTIs/100 trainees (p = 0.185). Hospitalization rates per diagnosed SSTI decreased from 18.4% to 7.2% (p = 0.009). Average length of hospitalization decreased from 9.01 days to 4.33 days (p = 0.034). Doxycycline prophylaxis was associated with decreased frequency and severity of hospitalization for SSTIs among this population.
Collapse
|
|
4
|
Bierbrier R, D’Aguanno K, Oliel S, Zeng Y, Esfahani K, Pehr K. An Analysis of Risk Factors for the Development of Acneiform Eruptions in Patients on Monoclonal Antibody Epidermal Growth Factor Receptor Inhibitors. J Cutan Med Surg 2023; 27:614-620. [PMID: 37942582 PMCID: PMC10714707 DOI: 10.1177/12034754231211326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 09/17/2023] [Indexed: 11/10/2023]
Abstract
Acneiform eruptions occur frequently and early in patients on epidermal growth factor receptor inhibitors (EGFRi). Identification of baseline patient risk factors would prompt earlier referral to dermatology to optimize prevention and management. The primary objective of this retrospective study is to determine the association between clinical and demographic characteristics and the development of acneiform eruptions. A retrospective chart review was conducted on patients diagnosed with colon and head and neck cancers who started EGFRi between January 2017 and December 2021. Patients were followed until death or September 2022. Baseline demographic and clinical parameters were documented and patients were followed from the time of diagnosis to most recent visit for the development and management of an acneiform eruption. Regression analyses were performed to determine the association between baseline characteristics and the development of acneiform eruptions. A total of 66 patients were treated with cetuximab or panitumumab between 2017-2021 were included in the analysis. Forty-seven of the sixty-six patients developed an acneiform eruption while on EGFRi therapy (71.2%). Combination cancer therapy with another chemotherapeutic agent was associated with a lower risk of acneiform eruption (OR 0.03, P = .027). No other baseline features were statistically associated with a lower risk of acneiform eruption. Acneiform eruptions are a common cutaneous adverse event of EGFRi therapy. Ongoing research is required to elucidate risk factors for the development of acneiform eruptions, to improve the quality of life of oncology patients.
Collapse
Affiliation(s)
- Rachel Bierbrier
- Division of Dermatology, McGill University, Montreal, QC, Canada
| | | | - Sarah Oliel
- Faculty of Medicine, McGill University, Montreal, QC, Canada
| | - Yixiao Zeng
- Quantitative Life Sciences Program, Interfaculty Studies, McGill University, Montréal, Qc, Canada
- Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, QC, Canada
| | - Khashayar Esfahani
- St Mary’s Hospital, McGill University, Montreal, QC, Canada
- Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montreal, QC, Canada
| | - Kevin Pehr
- Division of Dermatology, McGill University, Montreal, QC, Canada
- Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montreal, QC, Canada
| |
Collapse
|
|
5
|
Iwasaku M, Uchino J, Chibana K, Tanzawa S, Yamada T, Tobino K, Uchida Y, Kijima T, Nakatomi K, Izumi M, Tamiya N, Kimura H, Fujita M, Honda R, Takumi C, Yamada T, Kaneko Y, Kiyomi F, Takayama K. Prophylactic treatment of dacomitinib-induced skin toxicities in epidermal growth factor receptor-mutated non-small-cell lung cancer: A multicenter, Phase II trial. Cancer Med 2023; 12:15117-15127. [PMID: 37269194 PMCID: PMC10417098 DOI: 10.1002/cam4.6184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 05/18/2023] [Accepted: 05/20/2023] [Indexed: 06/04/2023] Open
Abstract
BACKGROUND Dacomitinib significantly improves progression-free survival and overall survival (OS) compared with gefitinib in patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)-activating mutations. However, dacomitinib often causes skin toxicities, resulting in treatment discontinuation. We aimed to evaluate a prophylactic strategy for skin toxicity induced by dacomitinib. METHODS We performed a single-arm, prospective, open-label, multi-institutional phase II trial for comprehensive skin toxicity prophylaxis. Patients with NSCLC harboring EGFR-activating mutations were enrolled and received dacomitinib with comprehensive prophylaxis. The primary endpoint was the incidence of skin toxicity (Grade ≥2) in the initial 8 weeks. RESULTS In total, 41 Japanese patients participated between May 2019 and April 2021 from 14 institutions (median age 70 years; range: 32-83 years), 20 were male, and 36 had a performance status of 0-1. Nineteen patients had exon 19 deletions and L858R mutation. More than 90% of patients were perfectly compliant with prophylactic minocycline administration. Skin toxicities (Grade ≥2) occurred in 43.9% of patients (90% confidence interval [CI], 31.2%-56.7%). The most frequent skin toxicity was acneiform rash in 11 patients (26.8%), followed by paronychia in five patients (12.2%). Due to skin toxicities, eight patients (19.5%) received reduced doses of dacomitinib. The median progression-free survival was 6.8 months (95% CI, 4.0-8.6 months) and median OS was 21.6 months (95% CI, 17.0 months-not reached). CONCLUSION Although the prophylactic strategy was ineffective, the adherence to prophylactic medication was quite good. Patient education regarding prophylaxis is important and can lead to improved treatment continuity.
Collapse
Affiliation(s)
- Masahiro Iwasaku
- Department of Pulmonary Medicine, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
| | - Junji Uchino
- Department of Pulmonary Medicine, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
| | - Kenji Chibana
- Department of Respiratory MedicineNational Hospital Organization Okinawa National HospitalOkinawaJapan
| | - Shigeru Tanzawa
- Division of Medical Oncology, Department of Internal MedicineTeikyo University School of MedicineTokyoJapan
| | - Takahiro Yamada
- Department of Pulmonary MedicineMatsushita Memorial HospitalOsakaJapan
| | - Kazunori Tobino
- Department of Respiratory MedicineIizuka HospitalIizukaJapan
| | - Yasuki Uchida
- Division of Respiratory Medicine, Department of Internal MedicineShiga University of Medical ScienceJapan
| | - Takashi Kijima
- Department of Respiratory Medicine and HematologyHyogo Medical University, School of MedicineHyogoJapan
| | - Katsumi Nakatomi
- Department of Respiratory MedicineNational Hospital Organization Ureshino Medical CenterUreshinoJapan
| | - Miiru Izumi
- Department of Respiratory MedicineNational Hospital Organization, Omuta National HospitalFukuokaJapan
| | - Nobuyo Tamiya
- Department of Pulmonary MedicineRakuwakai Otowa HospitalKyotoJapan
| | - Hideharu Kimura
- Department of Respiratory MedicineKanazawa University HospitalIshikawaJapan
| | - Masaki Fujita
- Department of Respiratory MedicineFukuoka University HospitalFukuokaJapan
| | - Ryoichi Honda
- Department of Respiratory MedicineAsahi General HospitalAsahiJapan
| | - Chieko Takumi
- Department of Respiratory MedicineJapanese Red Cross Kyoto Daiichi HospitalKyotoJapan
| | - Tadaaki Yamada
- Department of Pulmonary Medicine, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
| | - Yoshiko Kaneko
- Department of Pulmonary Medicine, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
| | - Fumiaki Kiyomi
- Statistics and Data Center, Clinical Research Support Center KyushuFukuokaJapan
| | - Koichi Takayama
- Department of Pulmonary Medicine, Graduate School of Medical ScienceKyoto Prefectural University of MedicineKyotoJapan
| |
Collapse
|
|
6
|
Recuero JK, Fitz JR, Pereira AA, Bonamigo RR. EGFR inhibitors: clinical aspects, risk factors and biomarkers for acneiform eruptions and other mucosal and cutaneous adverse effects. An Bras Dermatol 2023:S0365-0596(23)00051-X. [PMID: 36990917 DOI: 10.1016/j.abd.2022.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 09/20/2022] [Accepted: 10/01/2022] [Indexed: 03/29/2023] Open
Abstract
The frequency of the use of drugs that act on the epidermal growth factor receptor (EGFR) is increasing, with the consequent onset of cutaneous toxicity, specifically acneiform eruption. The authors extensively review the topic, focusing on describing how these drugs can affect the skin and its appendages, that is, the pathophysiology that encompasses the cutaneous toxicity related to the use of EGFR inhibitors. In addition, it was possible to list the risk factors that may be associated with adverse effects of these drugs. Based on this recent knowledge, the authors expect to aid in the management of patients who are more vulnerable to toxicity, reduce morbidities, and improve the quality of life of patients undergoing treatment with EGFR inhibitors. Other issues related to the toxicity of EGFR inhibitors, such as the clinical aspects of the acneiform eruption grades, and other different types of cutaneous and mucosal reactions, are also included in the article.
Collapse
Affiliation(s)
- Júlia Kanaan Recuero
- Postgraduate program in Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil; Dermatology Service, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brazil.
| | - Joana Roberta Fitz
- Dermatology Service, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brazil
| | - Andrea Abe Pereira
- Postgraduate program in Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil
| | - Renan Rangel Bonamigo
- Postgraduate program in Pathology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil; Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| |
Collapse
|
|
7
|
A phase 2 study for evaluating doxycycline 50 mg once daily and 100 mg once daily as preemptive treatment for skin toxicity in patients with metastatic colorectal cancer treated with an anti-EGFR and chemotherapy. Support Care Cancer 2022; 30:8081-8088. [PMID: 35776185 DOI: 10.1007/s00520-022-07254-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 06/23/2022] [Indexed: 10/17/2022]
Abstract
PURPOSE To assess the efficacy, safety, and quality-of-life outcomes of doxycycline 50 or 100 mg once daily in the prevention of skin toxicity in patients undergoing chemotherapy plus anti-EGFR therapy as first-line treatment of metastatic colorectal cancer (mCRC). METHODS Phase II, multicenter, single-arm, exploratory study was conducted in 7 Spanish hospitals. The primary study outcome was the incidence of ≥ grade 2 skin toxicities during the 6-week skin treatment period. Quality of life was assessed with the Dermatology Life Quality Index (DLQI) questionnaire. Patients had to receive either doxycycline 50 mg once daily in a first stage with 10 patients, or, if more than three patients presented ≥ grade 2 skin toxicities, the next 30 patients had to receive 100 mg once daily. RESULTS Thirty-four patients with RAS wild-type mCRC were enrolled in the study. Ten patients were first treated with doxycycline 50 mg once daily, and the following 24 were treated with doxycycline 100 mg once daily. A total of 60.0% (95% CI 29.6-90.0) and 20.8% (95% CI 4.6-37.0) of patients who received doxycycline 50 mg/day and 100 mg/day, respectively, had at least one ≥ grade 2 skin toxicity. Patients treated with doxycycline 100 mg once daily experienced less QoL deterioration. Only 1 patient reported a mild doxycycline-related gastrointestinal adverse event. CONCLUSION Our results suggest that doxycycline doses as low as 100 mg once daily are efficacious and well tolerated for the prevention of skin toxicity in patients with mCRC who undergo treatment with chemotherapy plus EGFR-targeted therapies. TRIAL REGISTRATION ClinicalTrials.gov NCT03448731.
Collapse
|
|
8
|
Nakata K, Komori T, Saso K, Ota H, Kagawa Y, Morita S, Noura S, Hayashi N, Uemura M, Matsuda C, Satoh T, Mizushima T, Murata K, Doki Y, Eguchi H. Pre-emptive oral clarithromycin reduces the skin toxicity of panitumumab treatment for metastatic colorectal cancer. Int J Colorectal Dis 2021; 36:2621-2627. [PMID: 34345969 DOI: 10.1007/s00384-021-04002-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/27/2021] [Indexed: 02/04/2023]
Abstract
PURPOSE Chemotherapy with panitumumab is expected to be well tolerated and improve survival in patients with metastatic colorectal cancer (mCRC). However, skin toxicities are its most common adverse events. The aim of this trial was to evaluate the efficacy and safety of pre-emptive antibiotic treatment with clarithromycin (CAM) to prevent panitumumab skin toxicities. METHODS We conducted a phase lll, multicenter, open-label, randomized clinical trial on mCRC patients treated with panitumumab. Eligible patients were randomly assigned 1:1 to pre-emptive antibiotic and control groups. In the pre-emptive group, CAM administration (200 mg twice per day) continued daily through the panitumumab treatment period. The control regimen consisted of skin care only. The primary end point was the incidence of grade ≥ 2 skin toxicities during the 6-week skin treatment period. RESULTS Of 156 enrolled patients, 78 received pre-emptive antibiotic treatment, and 78 received reactive treatment. The number and incidence of grade ≥ 2 skin toxicities during the 6-week skin treatment period were 16 (21.3%) and 41 (54.7%) for the pre-emptive and control groups, respectively (HR, 0.32; 95% CI, 0.17-0.56). There was almost no difference in the rate of other adverse events between the two groups, but the incidence of grade ≥ 3 diarrhea in the pre-emptive group was high, at 8% vs. 1.3% in the control group. There were no treatment-related deaths. CONCLUSION Prophylactic oral CAM together with relatively simple skin care was found to be effective in suppressing the development of grade ≥ 2 skin toxicities induced by panitumumab. CLINICAL TRIAL REGISTRATION UMIN000011485 DATE OF REGISTRATION: Sep 1st, 2013.
Collapse
Affiliation(s)
- Ken Nakata
- Department of Surgery, Sakai City Medical Center, Ebaraji-cho 1-1-1, Nishi-ku, Sakai, Osaka, Japan.
| | - Takamichi Komori
- Department of Gastroenterological Surgery, Hyogo Prefectural Nishinomiya Hospital, Rokutanji-cho 13-9, Nishinomiya, Hyogo, Japan
| | - Kazuhiro Saso
- Department of Surgery, Ashiya Municipal Hospital, Asahigaoka-cho 39-1, Ashiya, Hyogo, Japan
| | - Hirofumi Ota
- Department of Gastroenterological Surgery, Ikeda City Hospital, Jounan 3-1-18, Ikeda, Osaka, Japan
| | - Yoshinori Kagawa
- Department of Gastroenterological Surgery, Osaka General Medical Center, Mandaihigashi 3-1-56, Sumiyoshi-ku, Osaka, Japan
| | - Shunji Morita
- Department of Surgery, Itami City Hospital, Koyaike 1-100, Itami, Hyogo, Japan
| | - Shingo Noura
- Department of Surgery, Toyonaka Municipal Hospital, Shibahara-cho 4-14-1, Toyonaka, Osaka, Japan
| | - Nobuyasu Hayashi
- Department of Surgery, Kinan Hospital, Shinjo-cho 46-70, Tanabe, Wakayama, Japan
| | - Mamoru Uemura
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, Japan
| | - Chu Matsuda
- Department of Surgery, Toyonaka Municipal Hospital, Shibahara-cho 4-14-1, Toyonaka, Osaka, Japan
| | - Taroh Satoh
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, Japan
| | - Tsunekazu Mizushima
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, Japan
| | - Kohei Murata
- Department of Surgery, Itami City Hospital, Koyaike 1-100, Itami, Hyogo, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 E2 Yamadaoka, Suita, Osaka, Japan
| |
Collapse
|
|
9
|
Pospischil I, Hoetzenecker W. Arzneimittelexantheme unter modernen zielgerichteten Therapien - Immuncheckpoint- und EGFR-Inhibitoren. J Dtsch Dermatol Ges 2021; 19:1621-1645. [PMID: 34811897 DOI: 10.1111/ddg.14641_g] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 08/19/2021] [Indexed: 12/12/2022]
Affiliation(s)
- Isabella Pospischil
- Universitätsklinik für Dermatologie und Venerologie, Kepler Universitätsklinikum, Johannes Kepler Universität, Linz, Österreich
| | - Wolfram Hoetzenecker
- Universitätsklinik für Dermatologie und Venerologie, Kepler Universitätsklinikum, Johannes Kepler Universität, Linz, Österreich
| |
Collapse
|
|
10
|
Pospischil I, Hoetzenecker W. Drug eruptions with novel targeted therapies - immune checkpoint and EGFR inhibitors. J Dtsch Dermatol Ges 2021; 19:1621-1643. [PMID: 34811916 PMCID: PMC9299005 DOI: 10.1111/ddg.14641] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 08/19/2021] [Indexed: 12/25/2022]
Abstract
Given the increasing use of novel targeted therapies, dermatologists are constantly confronted with novel cutaneous side effects of these agents. A rapid diagnosis and appropriate management of these side effects are crucial to prevent impairment of the patients' quality of life and interruptions of essential cancer treatments. Immune checkpoint and EGFR inhibitors are frequently used targeted therapies for various malignancies and are associated with a distinct spectrum of cutaneous adverse events. Exanthematous drug eruptions represent a particular diagnostic challenge in these patients. Immune checkpoint inhibitors can elicit a plethora of immune-related exanthemas, most commonly maculopapular, lichenoid, and psoriasiform eruptions. Additionally, autoimmune bullous dermatoses and exanthemas associated with connective tissue diseases may arise. In cases of severe, atypical or therapy-resistant presentations an extensive dermatological investigation including a skin biopsy is recommended. Topical and systemic steroids are the mainstay of treatment. Papulopustular eruptions represent the major cutaneous adverse effect of EGFR inhibitor therapy, occurring in up to 90 % of patients within the first two weeks of therapy, depending on the agent. Besides topical antibiotics and steroids, oral tetracyclines are the first choice in systemic treatment and can also be used as prophylaxis.
Collapse
Affiliation(s)
- Isabella Pospischil
- Department of Dermatology, Kepler University Hospital, Johannes Kepler University, Linz, Austria
| | - Wolfram Hoetzenecker
- Department of Dermatology, Kepler University Hospital, Johannes Kepler University, Linz, Austria
| |
Collapse
|
|
11
|
Kashiwa M, Matsushita R. Cost-effectiveness of preemptive skin treatment to prevent skin-toxicity caused by panitumumab in third-line therapy for KRAS wild type metastatic colorectal cancer in Japan. J Pharm Health Care Sci 2021; 7:35. [PMID: 34593037 PMCID: PMC8485424 DOI: 10.1186/s40780-021-00218-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 08/02/2021] [Indexed: 12/24/2022] Open
Abstract
Background Clinical management of skin-toxicity associated with the use of anti-Epidermal Growth Factor Receptor (EGFR) antibodies to treat colorectal cancer maintains quality of life of patients with colorectal cancer. Results of clinical trials have recommended the efficacy of prophylactic treatment, but the cost-effectiveness is unclear. This study examined the cost-effectiveness of preventive skin care for skin-toxicity caused by panitumumab in third-line therapy for KRAS wild type metastatic colorectal cancer from the perspective of the Japanese healthcare payer. Methods The data source was J-STEPP trial, which compared preemptive skin treatment with reactive treatment in third-line panitumumab therapy for KRAS wild type metastatic colorectal cancer in Japan. The costs and effectiveness of preemptive treatment was compared with reactive treatment in a 3-year time horizon using a 4-state partitioned survival analysis. The health outcome was quality-adjusted life-years (QALYs). The costs were 2020 revisions to the drug prices. The robustness of the model was verified by one-way sensitivity analysis and a probabilistic sensitivity analysis (PSA). A 2% annual discount was applied to the expenses and QALYs. Willingness-to-pay (WTP) threshold of 5 million JPY was used. Results Preemptive treatment had incremental effects of 0.0029 QALYs, incremental costs of 5300 JPY (48.6 USD), and incremental cost-effectiveness ratios (ICER) of 1,843,395 JPY (16,912 USD) per QALY. The variability of preemptive and reactive treatment costs for skin-toxicity and the disutility of skin-toxicity had a large impact on ICER. From PSA, the cost-effectiveness rate of preemptive treatment was 75.0%. Conclusions The cost to effectiveness of preemptive treatment to prevent skin-toxicity caused by panitumumab in third-line therapy for KRAS wild type mCRC is not high.
Collapse
Affiliation(s)
- Munenobu Kashiwa
- Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan.
| | - Ryo Matsushita
- Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan
| |
Collapse
|
|
12
|
Alanen V, Iivanainen S, Arffman M, Koivunen JP. Purchase of prophylactic topical corticosteroids is associated with improved survival in NSCLCs treated with EGFR TKI: real-world cohort study. Acta Oncol 2021; 60:1100-1105. [PMID: 34137354 DOI: 10.1080/0284186x.2021.1937309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
BACKGROUND With the first- and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), clinical benefit and rash correlate together. EGFR TKI-induced rash can be alleviated with topical corticosteroids and tetracyclines. This study investigates whether prophylaxis with topical corticosteroids is associated with improved survival among the EGFR TKI-treated non-small cell lung cancers (NSCLCs). MATERIAL AND METHODS We collected all the patients (n = 1271) who had received reimbursement for the first- or second-generation EGFR TKIs in Finland 2011-2016, had purchased TKIs, and had data available at the Finnish Cancer Registry (FCR). Survival was analyzed from the first EGFR TKI purchase to death or the end of follow-up, and patients were stratified according to the TKIs, purchases of topical corticosteroids, and their timing. RESULTS A total of 270 (21%) patients had corticosteroid purchases -14 to +200 d (all), and 196 (15%) had purchased corticosteroids as prophylaxis (-14 to +14 d) from the first EGFR TKI purchase. Corticosteroid purchases were associated with improved survival in all (0.64 95% CI 0.56-0.74) and prophylactic (0.78, 95% CI 0.66-0.92) groups when compared to non-purchasers, although these results were limited to the erlotinib users only. The survival benefit of prophylactic corticosteroids among the erlotinib users remained in multivariate analysis including sex, stage, histology, and tetracycline prophylaxis (HR 0.78, 95% CI 0.64-0.95). The prophylactic use of corticosteroids was associated with a longer erlotinib treatment duration (HR 0.75, 95% CI 0.64-0.90). CONCLUSIONS Prophylactic topical corticosteroids may improve the survival of NSCLC patients treated with EGFR TKIs, and they should be considered as prophylaxis when initiating EGFR TKIs with a high incidence of rash.
Collapse
Affiliation(s)
- Virve Alanen
- Department of Medical Oncology and Radiotherapy and Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
| | - Sanna Iivanainen
- Department of Medical Oncology and Radiotherapy and Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
| | - Martti Arffman
- Health and Social Systems Research Unit, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Jussi P. Koivunen
- Department of Medical Oncology and Radiotherapy and Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
| |
Collapse
|
|
13
|
Gundogan B, Dowlut N, Rajmohan S, Borrelli MR, Millip M, Iosifidis C, Udeaja YZ, Mathew G, Fowler A, Agha R. Assessing the compliance of systematic review articles published in leading dermatology journals with the PRISMA statement guidelines: A systematic review. JAAD Int 2021; 1:157-174. [PMID: 34409336 PMCID: PMC8361930 DOI: 10.1016/j.jdin.2020.07.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/15/2020] [Indexed: 11/24/2022] Open
Abstract
Background Reporting quality of systematic reviews and meta-analyses is of critical importance in dermatology because of their key role in informing health care decisions. Objective To assess the compliance of systematic reviews and meta-analyses in leading dermatology journals with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement guidelines. Methods This review was carried out in accordance with PRISMA guidelines. Included studies were reviews published across 6 years in the top 4 highest-impact-factor dermatology journals of 2017. Records and full texts were screened independently. Data analysis was conducted with univariate multivariable linear regression. The primary outcome was to assess the compliance of systematic reviews and meta-analyses in leading dermatology journals with the PRISMA statement. Results A total of 166 studies were included and mean PRISMA compliance across all articles was 73%. Compliance significantly improved over time (β = .016; P = <.001). The worst reported checklist item was item 5 (reporting on protocol existence), with a compliance of 15% of articles. Conclusion PRISMA compliance within leading dermatology journals could be improved; however, it is steadily improving.
Collapse
Affiliation(s)
- Buket Gundogan
- University College London Hospital, London, United Kingdom
| | - Naeem Dowlut
- Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
| | | | - Mimi R Borrelli
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California
| | - Mirabel Millip
- Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
| | - Christos Iosifidis
- Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
| | - Yagazie Z Udeaja
- Luton and Dunstable University Hospital NHS Foundation Trust, Luton, United Kingdom
| | - Ginimol Mathew
- University College London Medical School, Gower Street, London, United Kingdom
| | | | - Riaz Agha
- Bart's Health NHS Foundation Trust, London, United Kingdom
| |
Collapse
|
|
14
|
Alanen V, Iivanainen S, Arffman M, Koivunen JP. Tetracyclines increase the survival of NSCLC patients treated with EGFR TKIs: a retrospective nationwide registry study. ESMO Open 2021; 5:e000864. [PMID: 33087401 PMCID: PMC7580060 DOI: 10.1136/esmoopen-2020-000864] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 07/27/2020] [Accepted: 07/28/2020] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND With the first and second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), clinical benefit and rash correlate together. EGFR TKI-induced rash can be alleviated with tetracyclines, but it is unknown whether the use of tetracyclines can increase the survival of non-small-cell lung cancer (NSCLC) patients treated with EGFR TKIs. METHODS We collected all the patients (n=1271) who had reimbursement for EGFR TKIs (gefitinib, erlotinib and afatinib) in Finland 2011-2016, had purchased TKIs, and had data available at nationwide cancer registry. The survival was analysed from the first EGFR TKI purchase to death or end-of follow-up, and patients were stratified according to TKIs, purchases of antibiotics, their ATC class and timing. RESULTS 802 (63.1%) patients had antibiotic purchases -14 to +200 days from the first EGFR TKI purchase, 447 of these tetracyclines. 322 (25.3%) had had purchased antibiotics -14 to +14 days (prophylaxis) from the first EGFR TKI purchase, 188 of these tetracyclines. Purchase of antibiotics was associated with improved survival (HR 0.80, 95% CI 0.71 to 0.91), which limited to tetracycline purchases only (HR 0.72, 95% CI 0.64 to 0.82). The largest survival benefit was seen with the prophylactic use of tetracyclines (HR 0.74, 95% CI 0.62 to 0.88). The benefit from tetracyclines was limited to erlotinib only (HR 0.68, 95% CI 0.58 to 0.78) which was retained in multivariate analysis. Prophylactic use of tetracyclines was associated with a longer erlotinib treatment duration (HR 0.81, 95% CI 0.61 to 0.96) but not with dose reductions or treatment breaks. CONCLUSIONS Tetracyclines improve the survival of NSCLC patients treated with the first and second-generation EGFR TKIs and they should be considered as a prophylaxis when initiating EGFR TKIs with high incidence of rash.
Collapse
Affiliation(s)
- Virve Alanen
- Oncology and Radiotherapy, Pohjois-Pohjanmaan Sairaanhoitopiiri, Oulu, Finland; MRC Oulu, Oulu University, Oulu, Finland
| | - Sanna Iivanainen
- Oncology and Radiotherapy, Pohjois-Pohjanmaan Sairaanhoitopiiri, Oulu, Finland; MRC Oulu, Oulu University, Oulu, Finland
| | - Martti Arffman
- National Institute for Health and Welfare, Helsinki, Finland
| | - Jussi Pekka Koivunen
- Oncology and Radiotherapy, Pohjois-Pohjanmaan Sairaanhoitopiiri, Oulu, Finland; MRC Oulu, Oulu University, Oulu, Finland.
| |
Collapse
|
|
15
|
Supportive oncodermatology-a narrative review of its utility and the way forward. Support Care Cancer 2021; 29:4931-4937. [PMID: 33712911 DOI: 10.1007/s00520-021-06124-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 03/02/2021] [Indexed: 11/27/2022]
Abstract
Supportive oncodermatology is an interdisciplinary field, emerging due to increasing dermatological morbidity in patients with cancer and the recognition of the need for greater collaborative and integrated care to improve patient outcomes. These two unique fields (Oncology and Dermatology) may be integrated in various ways, such as through specialised combined clinics, protocols for expedited access, multidisciplinary groups and meetings, and the development of best practices guidelines. This narrative review consolidates the small but growing literature surrounding supportive oncodermatology; discusses the potential benefit and disadvantages, and areas for future research; and suggests a framework for implementation.
Collapse
|
|
16
|
The extent to which the last decade has yielded additional treatment options for EGFR-associated rash besides classic treatment with antibiotics and corticosteroids - A systematic review. Eur J Oncol Nurs 2021; 50:101896. [PMID: 33493993 DOI: 10.1016/j.ejon.2021.101896] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 12/20/2020] [Accepted: 01/03/2021] [Indexed: 12/27/2022]
Abstract
PURPOSE To investigate the effectiveness of different interventions for the prevention and treatment of EGFRI treatment-induced rash (EGFRIr) that appeared in the last decade, excluding antibiotics and steroids products alone. METHOD A systematic review was performed in 2019 and was updated in 2020. The search strategy was limited to studies published within the last 10 years on the Medline database accessed via Pubmed and the Cochrane database. The search was performed using keywords combined with AND, OR. RESULTS The search yielded thirteen studies. The studies were divided into two categories, based on the intervention method used: four studies used creams containing vitamin K1 or vitamin K3 (henceforth classified as "Category A″) and nine studies ("Category B″) focused on different intervention methods such as laser treatment, Polydatin (PD) cream treatment, treatment with sunscreen, Adapalene gel treatment, topical aloe vera treatment, topical hydration treatment, the impact of a pre-emptive skin treatment and, finally, epidermal growth factor (EGF) ointment treatment. From "Category A″, the results vary as two studies found no benefit from cream use, while two studies indicated a possible improvement on skin reactions from cream use. In "Category B″, a benefit due to laser treatment was indicated, Polydatin-containing moisturizer showed a reduction in the incidence of rash grade ≥ II in patients treated with afatinib, while treatment with sunscreen demonstrated no benefit for the prevention of EGFRIr. Additionally, Adapalene gel use is not recommended as prophylaxis for EGFRIr, topical aloe vera may be used in the management for EGFRIr due to cetuximab, topical hydration resolved the EFGRIr, the pre-emptive skin treatment routine was well tolerated and the epidermal growth factor ointment improved all the symptoms due to EGFRI. CONCLUSIONS The results from the studies vary, although this study focuses on reviewing treatment interventions that can be utilized, apart from antibiotics and steroids, in order to alleviate the problems of the patients suffering from EGFRIr. More specifically, the authors of this review cannot draw a conclusion from "Category A″, as the efficacy of vitamin K for the management of EGFRIr is controversial. From "Category B″, some of the suggested treatments show encouraging results, while others may prove ineffective and rather harmful for the patients.
Collapse
|
|
17
|
He C, Lin R, Zhang J, Sun L, Lin J, Lin L. Efficacy of treatment for acneiform eruptions related to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for non-small cell lung cancer (NSCLC): A protocol of systematic review and network meta-analysis. Medicine (Baltimore) 2021; 100:e23875. [PMID: 33429746 PMCID: PMC7793452 DOI: 10.1097/md.0000000000023875] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 11/24/2020] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Acneiform eruptions from epidermal growth factor receptor tyrosine kinase inhibitors is a frequent adverse event in non-small cell lung cancer patients but the efficacy of its treatment including antibiotics, corticosteroid, sunscreen is still poorly understood. METHODS Eight electronic databases (PubMed, EMBASE, ClinicalTrials.gov, etc) will be searched from inception to April 2020. Risk of bias of randomized controlled trials will be assessed in terms of the Risk of Bias 2 (RoB 2) tool. Eligible randomized controlled trials will be enrolled for a Bayesian network meta-analysis using R software. RESULTS This study is still ongoing and the results will be submitted and published in a peer-reviewed scientific journal. CONCLUSION We hope the results of this study will provide reliable evidence for the management of acneiform due to epidermal growth factor receptor tyrosine kinase inhibitors for non-small cell lung cancer. ETHICS AND DISSEMINATION Ethical approval is not applicable for this study is based on published trials. PROTOCOL REGISTRATION NUMBER CRD42020206724.
Collapse
Affiliation(s)
- Canfeng He
- The First Clinical Medical College, Guangzhou University of Chinese Medicine
| | - Ruiting Lin
- The First Clinical Medical College, Guangzhou University of Chinese Medicine
| | - Jing Zhang
- Department of Oncology Center, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Lingling Sun
- Department of Oncology Center, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jietao Lin
- Department of Oncology Center, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Lizhu Lin
- Department of Oncology Center, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| |
Collapse
|
|
18
|
Raimondi A, Corallo S, Lonardi S, Antoniotti C, Rimassa L, Amatu A, Tampellini M, Racca P, Murialdo R, Clavarezza M, Zaniboni A, Toscano G, Tomasello G, Petrelli F, Antonuzzo L, Giordano M, Cinieri S, Longarini R, Niger M, Antista M, Ambrosini M, Pagani F, Prisciandaro M, Randon G, de Braud F, Di Bartolomeo M, Pietrantonio F, Morano F. Systemic doxycycline for pre-emptive treatment of anti-EGFR-related skin toxicity in patients with metastatic colorectal cancer receiving first-line panitumumab-based therapy: a post hoc analysis of the Valentino study. Support Care Cancer 2021; 29:3971-3980. [PMID: 33392769 DOI: 10.1007/s00520-020-05972-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 12/22/2020] [Indexed: 01/09/2023]
Abstract
INTRODUCTION The combination of anti-EGFRs and doublet chemotherapy is considered the optimal upfront option for patients with RAS/BRAF wild-type left-sided metastatic colorectal cancer (mCRC). The prophylactic or reactive treatment with tetracyclines for EGFR inhibitor-induced skin toxicity is currently clinical practice, though non-conclusive results are available. METHODS We performed a post hoc analysis of the Valentino study that randomized RAS wild-type mCRC patients to two panitumumab-based maintenance regimens after the first-line induction, aimed at assessing the safety and efficacy of the administration of a pre-emptive doxycycline prophylaxis for anti-EGFR-related skin toxicity. We assessed the rate of treatment-related and panitumumab-related adverse events (AEs), treatment intensity, progression-free survival (PFS), and overall survival (OS). RESULTS A total of 226 patients, out of the 229 enrolled in the Valentino study, were eligible for the analysis. Overall, 143 (63%) and 83 (37%) patients received or not the antibiotic prophylaxis for skin toxicity. Any grade and G3/4 panitumumab-related AEs were reported in 89% versus 92% (p = 0.650) and 27% versus 27% (p = 1.000) patients who received or not the pre-emptive prophylaxis, respectively. Any grade and G3/4 skin rash occurred in 81% versus 90% (p = 0.085) and 27% versus 25% (p = 0.876) patients receiving or not the prophylaxis, respectively. No significant differences in terms of treatment duration, treatment delays or dose reductions, PFS, and OS were observed in the two sub-populations. CONCLUSION The adequate management of anti-EGFR-related skin toxicity is fundamental to optimize the outcome of mCRC patients, balancing the survival benefit with patients' quality of life, especially in the first-line setting.
Collapse
Affiliation(s)
- Alessandra Raimondi
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, via Giacomo Venezian 1, 20133, Milan, Italy
| | - Salvatore Corallo
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, via Giacomo Venezian 1, 20133, Milan, Italy
| | - Sara Lonardi
- Medical Oncology Unit 1, Department of Oncology, Istituto Oncologico Veneto-IRCCS, Padua, Italy
| | - Carlotta Antoniotti
- Unit of Medical Oncology, Department of Translational Research and New Technologies in Medicine, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, Pisa, Italy
| | - Lorenza Rimassa
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center, IRCCS, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Alessio Amatu
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Marco Tampellini
- Department of Oncology, AOU San Luigi di Orbassano, University of Torino, Orbassano, Italy
| | - Patrizia Racca
- Colorectal Cancer Unit, Medical Oncology Division 1, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza, Turin, Italy
| | - Roberto Murialdo
- Department of Internal Medicine, University of Genoa and IRCCS AOU San Martino-IST, Genoa, Italy
| | - Matteo Clavarezza
- Medical Oncology Unit, Ente Ospedaliero Ospedali Galliera, Genoa, Italy
| | | | - Giuseppe Toscano
- Medical Oncology Unit A.O. Papardo & Department of Human Pathology, University of Messina, Messina, Italy
| | | | - Fausto Petrelli
- Medical Oncology Unit, Oncology Department, ASST Bergamo Ovest, Treviglio, Italy
| | - Lorenzo Antonuzzo
- Clinical Oncology Unit, AOU Careggi, Florence, Italy
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Monica Giordano
- Medical Oncology Unit, Azienda Socio Sanitaria Territoriale Lariana, Como, Italy
| | - Saverio Cinieri
- Medical Oncology Unit, Ospedale Antonio Perrino, Brindisi, Italy
| | | | - Monica Niger
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, via Giacomo Venezian 1, 20133, Milan, Italy
| | - Maria Antista
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, via Giacomo Venezian 1, 20133, Milan, Italy
| | - Margherita Ambrosini
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, via Giacomo Venezian 1, 20133, Milan, Italy
| | - Filippo Pagani
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, via Giacomo Venezian 1, 20133, Milan, Italy
| | - Michele Prisciandaro
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, via Giacomo Venezian 1, 20133, Milan, Italy
- Oncology and Hemato-oncology Department, University of Milan, via Festa del Perdono 7, 20122, Milan, Italy
| | - Giovanni Randon
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, via Giacomo Venezian 1, 20133, Milan, Italy
| | - Filippo de Braud
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, via Giacomo Venezian 1, 20133, Milan, Italy
- Oncology and Hemato-oncology Department, University of Milan, via Festa del Perdono 7, 20122, Milan, Italy
| | - Maria Di Bartolomeo
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, via Giacomo Venezian 1, 20133, Milan, Italy
| | - Filippo Pietrantonio
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, via Giacomo Venezian 1, 20133, Milan, Italy.
- Oncology and Hemato-oncology Department, University of Milan, via Festa del Perdono 7, 20122, Milan, Italy.
| | - Federica Morano
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, via Giacomo Venezian 1, 20133, Milan, Italy
| |
Collapse
|
|
19
|
Amitay-Laish I, Prag-Naveh H, Ollech A, Davidovici B, Leshem YA, Snast I, Popovtzer A, Purim O, Flex D, David M, Brenner B, Ben-Aharon I, Peled N, Hodak E, Stemmer SM. Prophylactic Topical Treatment for EGFR Inhibitor-Induced Papulopustular Rash: A Randomized Clinical Trial. Dermatology 2020; 237:988-994. [PMID: 33378750 DOI: 10.1159/000511869] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Accepted: 09/29/2020] [Indexed: 12/28/2022] Open
Abstract
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.
Collapse
Affiliation(s)
- Iris Amitay-Laish
- Division of Dermatology, Rabin Medical Center, Petah Tikva, Israel, .,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel,
| | - Hadas Prag-Naveh
- Division of Dermatology, Rabin Medical Center, Petah Tikva, Israel
| | - Ayelet Ollech
- Division of Dermatology, Rabin Medical Center, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Batya Davidovici
- Division of Dermatology, Rabin Medical Center, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Yael Anne Leshem
- Division of Dermatology, Rabin Medical Center, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Igor Snast
- Division of Dermatology, Rabin Medical Center, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Aron Popovtzer
- Institute of Oncology, Davidoff Cancer Center, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Ofer Purim
- Institute of Oncology, Davidoff Cancer Center, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Dov Flex
- Institute of Oncology, Davidoff Cancer Center, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Michael David
- Division of Dermatology, Rabin Medical Center, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Baruch Brenner
- Institute of Oncology, Davidoff Cancer Center, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Irit Ben-Aharon
- Institute of Oncology, Davidoff Cancer Center, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Nir Peled
- Institute of Oncology, Davidoff Cancer Center, Petah Tikva, Israel.,The Legacy Heritage Oncology Center and Dr. Larry Norton Institute, Soroka Medical Center and Ben-Gurion University, Beer-Sheva, Israel
| | - Emmillia Hodak
- Division of Dermatology, Rabin Medical Center, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Salomon M Stemmer
- Institute of Oncology, Davidoff Cancer Center, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| |
Collapse
|
|
20
|
Labadie JD, Hua X, Harrison TA, Banbury BL, Huyghe JR, Sun W, Shi Q, Yothers G, Alberts SR, Sinicrope FA, Goldberg RM, George TJ, Penney KL, Phipps AI, Cohen SA, Peters U, Chan AT, Newcomb PA. Genetic Predictors of Severe Skin Toxicity in Patients with Stage III Colon Cancer Treated with Cetuximab: NCCTG N0147 (Alliance). Cancer Epidemiol Biomarkers Prev 2020; 30:404-411. [PMID: 33203692 DOI: 10.1158/1055-9965.epi-20-1274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Revised: 10/16/2020] [Accepted: 11/12/2020] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Cetuximab, an EGFR inhibitor used to treat multiple cancer types, including colon cancer, causes severe skin toxicity in 5%-20% of patients, leading to decreased quality of life and treatment delays. Our understanding of which patients have an increased risk of severe toxicities is limited. We conducted a genome-wide association study to identify germline variants predictive of cetuximab-induced severe skin toxicity. METHODS Our study included 1,209 patients with stage III colon cancer randomized to receive cetuximab plus 5-fluorouracil and oxaliplatin as part of the NCCTG N0147 (Alliance) clinical trial. Skin toxicity outcomes were collected using the Common Toxicity Criteria for Adverse Events version 3.0. We performed genotyping, evaluating approximately 10 million genetic variants. We used logistic regression to evaluate the association of each genetic variant and severe (grade ≥ 3) skin toxicity, adjusting for age, sex, and genetic ancestry. Genome-wide significance was defined as P < 5 × 10-8. RESULTS Participants were predominantly middle-aged white men; 20% (n = 243) experienced severe skin toxicity. Two genetic variants in the retinoic acid receptor alpha (RARA) gene were significantly associated with severe skin toxicity [OR, 3.93; 95% confidence interval (CI), 2.47-6.25; P < 7.8 × 10-9]. Functional annotations indicate these variants are in the RARA promoter. Additional significantly associated variants were identified in chromosome 2 intergenic regions. CONCLUSIONS Identified variants could represent a potential target for risk stratification of patients with colon cancer receiving cetuximab. IMPACT Retinoids have shown promise in the treatment of cetuximab-induced skin toxicity, so follow-up work could evaluate whether individuals with the RARA variant would benefit from retinoid therapy.
Collapse
Affiliation(s)
- Julia D Labadie
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.,School of Public Health, University of Washington, Seattle, Washington
| | - Xinwei Hua
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.,School of Public Health, University of Washington, Seattle, Washington
| | - Tabitha A Harrison
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Barbara L Banbury
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Jeroen R Huyghe
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Wei Sun
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Qian Shi
- Department of Health Science Research, Mayo Clinic, Rochester, Minnesota.,Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota
| | - Greg Yothers
- NRG Oncology, Pittsburgh, Pennsylvania.,Biostatistics Department, University of Pittsburgh, Pittsburgh, Pennsylvania
| | | | - Frank A Sinicrope
- Department of Health Science Research, Mayo Clinic, Rochester, Minnesota
| | | | - Thomas J George
- NRG Oncology, Pittsburgh, Pennsylvania.,Department of Medicine, University of Florida, Gainesville, Florida
| | - Kathryn L Penney
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Amanda I Phipps
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.,School of Public Health, University of Washington, Seattle, Washington
| | - Stacey A Cohen
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.,Division of Oncology, University of Washington School of Medicine, Seattle, Washington
| | - Ulrike Peters
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.,School of Public Health, University of Washington, Seattle, Washington
| | - Andrew T Chan
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.,Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Polly A Newcomb
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. .,School of Public Health, University of Washington, Seattle, Washington
| |
Collapse
|
|
21
|
Suh HJ, Flórez Á, Sacristán V, Rodríguez Martinez Á, Fernández F, Vilanova-Trillo L, Constenla M, Pereiro M. Cutaneous adverse events in patients receiving anticancer therapy in a tertiary hospital setting: the old and the new. Int J Dermatol 2020; 60:208-216. [PMID: 33502780 DOI: 10.1111/ijd.15081] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 06/11/2020] [Accepted: 07/01/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND Targeted therapies and immunotherapies are increasingly prescribed, but classic chemotherapy agents are still highly used in cancer treatment. Both therapies, the old and the new, are associated with cutaneous adverse events (CAEs) that can cause treatment interruptions or reduce the quality of life of patients. METHODS An observational, cross-sectional, single-center study that included consecutive cancer patients presenting CAEs. The main objective was to describe CAEs derived from antineoplastic drugs. Secondary objectives were to determine the number and severity of CAEs and if there were differences regarding CAEs between conventional chemotherapeutics and targeted therapies. RESULTS A total of 114 patients were included with a total number of 177 CAEs. Of the 114 patients, 64 presented a single CAE, 37 patients had two CAEs, and 13 patients presented three CAEs. The most frequent CAEs were pruritus, xerosis, palmar-plantar erythrodysesthesia (PPE), and alopecia. The majority of CAEs were mild (63.2%), followed by moderate (29.9%) and severe (6.7%) CAEs. Of the 114 patients, 103 (90.3%) received topical agents and 11 (9.7%) required systemic treatment for the management of CAEs. Prophylactic treatment for CAE was delivered to only 4/114 (3.5%) patients. No significant differences were found in the number or severity of CAEs between conventional chemotherapy and targeted therapy. CONCLUSIONS Close collaboration between oncologists and dermatologists is essential to start preventive measures on time, enhance patient education, and avoid unnecessary dose reductions or treatment interruptions. The multidisciplinary approach can offer better management of skin toxicities.
Collapse
Affiliation(s)
- Hae-Jin Suh
- Dermatology Department, Pontevedra University Hospital, Pontevedra, Spain
| | - Ángeles Flórez
- Dermatology Department, Pontevedra University Hospital, Pontevedra, Spain
| | - Víctor Sacristán
- Medical Oncology Department, A Coruña University Hospital, A Coruña, Spain
| | | | | | | | - Manuel Constenla
- Medical Oncology Department, Pontevedra University Hospital, Pontevedra, Spain
| | - Manuel Pereiro
- Surgical Medical Specialties Department, Dermatology Section, Santiago de Compostela University, Santiago de Compostela, Spain
| |
Collapse
|
|
22
|
Ruiz-Camps I, Aguilar-Company J. Epidermal Growth Factor Receptor Inhibitors and Other Tyrosine Kinase Inhibitors for Solid Tumors. Infect Dis Clin North Am 2020; 34:257-270. [PMID: 32334988 DOI: 10.1016/j.idc.2020.02.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
This article analyzes the risk of infection associated with small molecule kinase inhibitors used to treat solid organ malignancies and establishes specific recommendations. Most of these drugs are orally administered and have the ability to inhibit distinct kinases, which play a major role in cancer initiation and progression. Although the true extent of adverse events is not yet known, risk of infection does not seem to be a major problem with these drugs. Because of the limited clinical experience and the constant evolution of targeted therapies, recommendations may evolve in the near future.
Collapse
Affiliation(s)
- Isabel Ruiz-Camps
- Infectious Diseases Department, Vall d'Hebron University Hospital, Passeig de la Vall d'Hebron, 119-129, Barcelona 08035, Spain
| | - Juan Aguilar-Company
- Infectious Diseases Department, Vall d'Hebron University Hospital, Passeig de la Vall d'Hebron, 119-129, Barcelona 08035, Spain; Oncology Department, Vall d'Hebron University Hospital, Passeig de la Vall d'Hebron, 119-129, Barcelona 08035, Spain.
| |
Collapse
|
|
23
|
Annunziata MC, De Stefano A, Fabbrocini G, Leo S, Marchetti P, Romano MC, Romano I. Current Recommendations and Novel Strategies for the Management of Skin Toxicities Related to Anti-EGFR Therapies in Patients with Metastatic Colorectal Cancer. Clin Drug Investig 2020; 39:825-834. [PMID: 31264159 DOI: 10.1007/s40261-019-00811-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
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.
Collapse
Affiliation(s)
- Maria Carmela Annunziata
- Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Alfonso De Stefano
- SC Oncologia Clinica Sperimentale Addome, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, Italy
| | - Gabriella Fabbrocini
- Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Silvana Leo
- Medical Oncology Unit, Ospedale Vito Fazzi, Lecce, Italy
| | - Paolo Marchetti
- Oncology Unit, Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy.
- IDI-IRCCS, Rome, Italy.
| | | | - Ivana Romano
- Dermatologist, UOC Oncologia, Ospedale "Sacro Cuore di Gesù" Gallipoli - Progetto Lilt, Lecce, Italy
| |
Collapse
|
|
24
|
Kim YS, Ji JH, Oh SY, Lee S, Huh SJ, Lee JH, Song K, Son CH, Roh MS, Lee GW, Lee J, Kim ST, Kim CK, Jang JS, Hwang IG, Ahn HK, Park LC, Oh SY, Kim S, Lee S, Lim D, Lee SI, Kang JH. A Randomized Controlled Trial of Epidermal Growth Factor Ointment for Treating Epidermal Growth Factor Receptor Inhibitor-Induced Skin Toxicities. Oncologist 2020; 25:e186-e193. [PMID: 31492766 PMCID: PMC6964120 DOI: 10.1634/theoncologist.2019-0221] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Accepted: 07/18/2019] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND The efficacy of epidermal growth factor (EGF) receptor (EGFR) inhibitors in patients with non-small cell lung cancer (NSCLC), pancreatic cancer (PC), or colorectal cancer (CRC) has been demonstrated. However, dermatological reactions to these inhibitors can cause significant physical and psychosocial discomfort. The objective of the present study was to evaluate the efficacy of EGF ointment for EGFR inhibitor-related skin adverse events (ERSEs). MATERIALS AND METHODS This placebo-controlled, double-blind, multicenter, pilot phase III trial enrolled patients with NSCLC, PC, or CRC treated with EGFR inhibitors. Patients with grade ≥2 ERSEs were included. Patients were randomized to three treatment arms: arm 1, placebo; arm 2, 1 ppm of EGF ointment; and arm 3, 20 ppm of EGF ointment. Patients applied ointment to their skin lesions twice daily. RESULTS Efficacy evaluation was available for 80 patients (9 for PC, 28 for NSCLC, and 43 for CRC). Responses were 44.4% in arm 1, 61.5% in arm 2, and 77.8% in arm 3. There was a linear correlation between EGF concentrations and responses (p = .012). Quality of life (QoL) was assessed for 74 patients. Maximum changes in composite scores by Skindex-16 after treatment were significantly different among arms (mean ± SD: -5.2 ± 8.6 for arm 1, -11.7 ± 14.2 for arm 2, and - 18.6 ± 17.7 for arm 3; p = .008). EGF arms showed significant improvement in emotions (p = .005) and functioning (p = .044) scores over the placebo arm. CONCLUSION EGF ointment is effective for managing ERSEs. It can also improve patients' QoL compared with placebo. Clinical trial identification number. NCT02284139 IMPLICATIONS FOR PRACTICE: Patients with non-small cell lung cancer, pancreatic cancer, or colorectal cancer who are treated with epidermal growth factor (EGF) receptor (EGFR) inhibitors may experience dermatologic reactions to their treatment. This study investigated the benefit of an EGF ointment in the treatment of these adverse events and observed the ointment to be effective in managing EGFR inhibitor-related skin adverse events.
Collapse
Affiliation(s)
- Young Saing Kim
- Department of Internal Medicine, Gachon University Gil Medical CenterIncheonRepublic of Korea
| | - Jun Ho Ji
- Division of Hematology‐Oncology, Samsung Changwon Hospital, Sungkyunkwan University School of MedicineChangwonRepublic of Korea
| | - Sung Yong Oh
- Department of Internal Medicine, Dong‐A University HospitalBusanRepublic of Korea
| | - Suee Lee
- Department of Internal Medicine, Dong‐A University HospitalBusanRepublic of Korea
| | - Seok Jae Huh
- Department of Internal Medicine, Dong‐A University HospitalBusanRepublic of Korea
| | - Ji Hyun Lee
- Department of Internal Medicine, Dong‐A University HospitalBusanRepublic of Korea
| | - Ki‐Hoon Song
- Department of Dermatology, National Cancer CenterGoyangRepublic of Korea
| | - Choon Hee Son
- Department of Pulmonology, Dong‐A University HospitalBusanRepublic of Korea
| | - Mee Sook Roh
- Department of Pathology, Dong‐A University College of MedicineBusanRepublic of Korea
| | - Gyeong Won Lee
- Department of Internal Medicine, Gyeongsang National University HospitalJinjuRepublic of Korea
| | - Jeeyun Lee
- Department of Medicine, Samsung Medical CenterSeoulRepublic of Korea
| | - Seung Tae Kim
- Department of Medicine, Samsung Medical CenterSeoulRepublic of Korea
| | - Chan Kyu Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon HospitalBucheonRepublic of Korea
| | - Joung Soon Jang
- Department of Internal Medicine, Chung‐Ang University College of MedicineSeoulRepublic of Korea
| | - In Gyu Hwang
- Department of Internal Medicine, Chung‐Ang University College of MedicineSeoulRepublic of Korea
| | - Hee Kyung Ahn
- Department of Internal Medicine, Gachon University Gil Medical CenterIncheonRepublic of Korea
| | - Lee Chun Park
- Division of Hematology‐Oncology, Department of Medicine, Kosin University College of MedicineBusanRepublic of Korea
| | - So Yeon Oh
- Department of Internal Medicine, Pusan National University Yangsan HospitalYangsanRepublic of Korea
| | - Seong‐Geun Kim
- Department of Internal Medicine, Pusan National University Yangsan HospitalYangsanRepublic of Korea
| | - Sang‐Cheol Lee
- Department of Internal Medicine, Soonchunhyang University Hospital CheonanCheonanRepublic of Korea
| | - Do‐Hyoung Lim
- Department of Internal Medicine, Dankook University College of MedicineCheonanRepublic of Korea
| | - Soon Il Lee
- Department of Internal Medicine, Dankook University College of MedicineCheonanRepublic of Korea
| | - Jung Hun Kang
- Department of Internal Medicine, Gyeongsang National University HospitalJinjuRepublic of Korea
| |
Collapse
|
|
25
|
Bouché O, Ben Abdelghani M, Labourey JL, Triby S, Bensadoun RJ, Jouary T, Des Guetz G. Management of skin toxicities during panitumumab treatment in metastatic colorectal cancer. World J Gastroenterol 2019; 25:4007-4018. [PMID: 31413534 PMCID: PMC6689814 DOI: 10.3748/wjg.v25.i29.4007] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Revised: 02/07/2019] [Accepted: 02/23/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Anti-epidermal growth factor receptor therapy is associated with skin adverse events not previously reported with conventional chemotherapy. Prophylactic actions are recommended, but routine clinical management of these toxicities and their impact on quality of life remain unknown.
AIM To assess the dermatological toxicities reported after panitumumab initiation, their impact on the quality of life and the clinical practices for their management.
METHODS Patients included in this prospective multicenter observational study were over 18 years of age and began treatment with panitumumab for wild-type KRAS metastatic colorectal cancer. The incidence of dermatological toxicities, clinical practices for their management and impact on quality of life were recorded during a 6-mo follow-up.
RESULTS Overall, 229 patients (males, 57.6%; mean age, 66.2 years) were included. At day 15, 59.3% of patients had dermatological toxicity; the rate peaked at month 2 (74.7%) and decreased at month 6 (46.5%). The most frequent dermatological toxicities were rash/acneiform rash, xerosis and skin cracks. At least one preventive treatment was administered to 65.9% of patients (oral antibiotics, 84.1%; emollients, 75.5%; both, 62.9%). The rates of patients who received at least one curative treatment peaked at month 2 (63.4%) and decreased at month 6 (44.8%). The impact of the dermatological toxicities on quality of life was limited as assessed with Dermatology Life Quality Index scores and inconvenience visual analogic scale score. The rates of topical corticosteroids administration and visits to specialists were low.
CONCLUSION The rates of the different skin toxicities peaked at various times and were improved at the end of follow-up. Nevertheless, their clinical management could be optimized with a better adherence to current recommendations. The impact of skin toxicities on patient’s quality of life appeared to be limited.
Collapse
Affiliation(s)
- Olivier Bouché
- Department of Gastroenterology and Digestive Oncology, Hôpital Robert Debré, CHU Reims, Reims 51000, France
| | | | | | - Simon Triby
- Medical Department, AMGEN France, Boulogne-Billancourt 92100, France
| | | | - Thomas Jouary
- Dermatology Department, Hôpital Saint-André, CHU de Bordeaux, Bordeaux 33000, France
| | | |
Collapse
|
|
26
|
A National Survey of Medical Oncologist's Opinions and Perceptions for Managing Rash Among mCRC Patients Treated with Panitumumab. Dermatol Ther (Heidelb) 2019; 9:337-353. [PMID: 31054146 PMCID: PMC6522609 DOI: 10.1007/s13555-019-0296-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Indexed: 10/27/2022] Open
Abstract
INTRODUCTION This study aimed to describe medical oncologist's opinions and perceptions regarding the management of dermatologic toxicities among metastatic colorectal cancer (mCRC) patients who were treated with panitumumab in the USA and assess if there were differences across demographic and clinical characteristics. METHODS We developed a survey based on the current literature and expert opinions regarding the management of dermatologic toxicities. The survey was implemented online in September 2016. Eligible oncologists were board certified and had treated at least five new or continuing patients with mCRC in the last 3 months, among whom at least three patients had received or were currently receiving panitumumab. RESULTS A total of 250 oncologists completed the survey. The data suggest that approximately 82% of patients received recommendations for moisturizer, 88% for sunscreen and 67% for ultraviolet (UV)-protective garments prior to or at the time of initiation of panitumumab therapy. There were minor differences in how dermatologic toxicities were managed across specific demographic or clinical groups. The data also suggest that the management associated with panitumumab use among mCRC patients can be greatly improved. CONCLUSIONS Our results highlight the urgent need for heightened education regarding dermatologic toxicity management among oncologists who treated mCRC patients with panitumumab. Easily implemented strategies, such as moisturizer, sunscreen, and UV-protective garments should be recommended to all patients. FUNDING Amgen, Inc. Plain language summary available for this article.
Collapse
|
|
27
|
Yalici-Armagan B, Ayanoglu BT, Demirdag HG. Targeted tumour therapy induced papulopustular rash and other dermatologic side effects: a retrospective study. Cutan Ocul Toxicol 2019; 38:261-266. [PMID: 31010330 DOI: 10.1080/15569527.2019.1594874] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Background: Papulopustular rash is the most common cutaneous adverse effect during targeted tumour therapy particularly with epidermal growth factor receptor inhibitors (EGFRIs). Objective: To evaluate the adverse skin reactions, mainly papulopustular rash, caused by targeted tumour therapy. Materials and methods: We retrospectively analysed the data of patients who were diagnosed papulopustular rash due to targeted chemotherapeutic agents between January 2016 and August 2018. Demographic characteristics of the patients, the type of malignancy, chemotherapeutic agents causing papulopustular rash, clinical features and grade of the rash, treatment modalities used for the rash, other associated cutaneous adverse reactions, and the need for dose-modification or discontinuation of the chemotherapy were recorded. Results: A total of 39 patients (26 males, 13 females) with a median age of 60 (range 32-86) years were included in the study. EGFRIs such as erlotinib, lapatinib, cetuximab, and panitumumab were the main drugs causing papulopustular rash in 2 (5.1%), 3 (7.6%), 18 (46.1%), and 13 (33.3%) patients, respectively. Imatinib, bevacizumab in combination with oxaliplatin, and everolimus in combination with exemestane and goserelin were responsible in three patients. The most commonly affected area was the face (87.1%) followed by the trunk (56.4%), scalp (25.6%), and extremities (23%). The rash was recorded as grade 1, 2, and 3 in 18, 13, and 6 of the patients, respectively. Grade 3 rash was lead to dose interruptions in 5 (12.8%) patients with subsequent reintroduction at a lower dose in 4 (10.2%) of them and discontinuation of the therapy in 1 (2.5%) patient. Pruritus, xerosis, paronychia, increased growth of the eyelashes, mucositis, hand-foot syndrome (HSF), and symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) are other skin toxicities associated with the targeted tumour therapy. Conclusions: With the increasing use of targeted therapies, dermatologists are now confronted with extensive spectrum of skin toxicities. Therefore, it is critical for dermatologists to be aware of these toxicities so as to develop the best approach without discontinuation of cancer therapy.
Collapse
Affiliation(s)
- Basak Yalici-Armagan
- a Department of Dermatology and Venereology, Faculty of Medicine, Hacettepe University , Ankara , Turkey
| | - Burcu Tugrul Ayanoglu
- b Department of Dermatology and Venereology, Abdurrahman Yurtaslan Oncology Training and Research Hospital , Ankara , Turkey
| | - Hatice Gamze Demirdag
- b Department of Dermatology and Venereology, Abdurrahman Yurtaslan Oncology Training and Research Hospital , Ankara , Turkey
| |
Collapse
|
|
28
|
Shacham Shmueli E, Geva R, Yarom N, Hubert A, Keynan R, Kedem TH, Eini M, Tamarkin D, Shirvan M. Topical doxycycline foam 4% for prophylactic management of epidermal growth factor receptor inhibitor skin toxicity: an exploratory phase 2, randomized, double-blind clinical study. Support Care Cancer 2019; 27:3027-3033. [PMID: 30607677 DOI: 10.1007/s00520-018-4600-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Accepted: 12/10/2018] [Indexed: 11/25/2022]
Abstract
PURPOSE Acneiform rash, a common toxicity of epidermal growth factor receptor inhibitors (EGFRIs), can cause patient discomfort, warranting changes in treatment. This study investigated the safety, tolerability, and efficacy of a novel doxycycline foam, FDX104 4%, for managing EGFRI-related skin toxicity. METHODS This was an exploratory phase 2, randomized, double-blind, placebo-controlled study. Subjects had metastatic colorectal cancer and were being treated with either cetuximab or panitumumab plus chemotherapy. Treatment (twice-daily topical FDX104 4% on one side of the face and vehicle foam on the other for 5 weeks) was initiated 7 ± 3 days prior to EGFRI therapy. Rash severity, safety, and tolerability were evaluated at 2 and 4 weeks after EGFRI start. RESULTS The mean maximal rash grade was lower with FDX104 4% vs vehicle, and fewer subjects developed moderate-to-severe (grades 2-3) rash. On the Global Severity Score scale, a statistically significant difference favored FDX104 4% over vehicle (P = .047). Adverse events (AEs) (n = 68) occurred in 20 subjects; most were mild or moderate. The most common AEs were oral mucositis, nausea, and vomiting, common to chemotherapy and EGFRI treatment. Study-drug-related AEs were experienced by five subjects and consisted of mild, local skin reactions. No study-drug-related systemic side effects were reported. CONCLUSION Twice-daily, topical administration of FDX104 4% as an adjunct to either cetuximab or panitumumab was safe and well tolerated, and appeared to prevent the onset of rash, especially severe rash. CLINICALTRIALS. GOV IDENTIFIER Trial Registration NCT02239731.
Collapse
Affiliation(s)
| | - Ravit Geva
- Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Nirit Yarom
- Assaf Harofeh Medical Center, Tzrifin, Israel
| | | | - Rita Keynan
- Foamix Pharmaceuticals Ltd., 2 Holzman Street, Weizmann-Science Park, 7670402, Rehovot, Israel
| | - Tal H Kedem
- Foamix Pharmaceuticals Ltd., 2 Holzman Street, Weizmann-Science Park, 7670402, Rehovot, Israel
| | - Meir Eini
- Foamix Pharmaceuticals Ltd., 2 Holzman Street, Weizmann-Science Park, 7670402, Rehovot, Israel
| | - Dov Tamarkin
- Foamix Pharmaceuticals Ltd., 2 Holzman Street, Weizmann-Science Park, 7670402, Rehovot, Israel
| | - Mitchell Shirvan
- Foamix Pharmaceuticals Ltd., 2 Holzman Street, Weizmann-Science Park, 7670402, Rehovot, Israel.
| |
Collapse
|
|
29
|
Chen P, Chen F, Zhou B. The risk of dermatological toxicities of combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma patients: a systematic review and meta-analysis. Cutan Ocul Toxicol 2018; 38:105-111. [PMID: 30501438 DOI: 10.1080/15569527.2018.1553180] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND This meta-analysis was conducted to assess the risk of dermatological toxicities of combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma patients. METHODS We considered relevant prospective randomized phase I, II, and III trials of melanoma patients on the combined BRAF and MEK inhibition versus BRAF inhibition, describing events of rash, photosensitivity reaction (PR), hyperkeratosis (HK), alopecia, cutaneous squamous-cell carcinom(cSCC), skin papilloma(SP), pruritus, and hand-foot syndrome(HFS), as eligible for inclusion. RESULTS Eight trials comprising 3163 patients were included in the meta-analysis. The relative risks(RRs) of developing all-grade rash with combined BRAF and MEK inhibition versus BRAF inhibition was 1.59 (95%CI, 1.35-1.86, p < 0.00001), HK 0.33(95%CI, 0.16-0.66, p = 0.002), SP 0.09(95%CI, 0.04-0.24, p < 0.00001), alopecia 0.30(95%CI, 0.19-0.48, p < 0.00001), cSCC 0.23(95%CI, 0.17-0.31, p < 0.00001), HFS 0.18(95%CI, 0.13-0.26, p < 0.00001) and PR 0.40(95%CI, 0.26-0.61, p < 0.0001), while the RRs of high-grade dermatological toxicities from all included trials were: rash 0.54(95%CI, 0.20-1.43, p = 0.21), HK 0.18(95%CI, 0.06-0.53, p = 0.002), SP 0.14(95%CI, 0.02-1.16, p = 0.07), alopecia 0.72(95%CI, 0.14-3.62, p = 0.69), cSCC 0.23(95%CI, 0.17-0.33, p < 0.00001), HFS 0.40(95%CI, 0.08-2.06, p = 0.27), and PR 0.14(95%CI, 0.04-0.51, p = 0.003), respectly. CONCLUSION Our analysis of data has demonstrated that combined BRAF and MEK inhibitor-based treatment is associated with an increased risk of all-grade rash and a decreased risk of all-grade and high-grade HK, SP, alopecia, cSCC, HFS, and PR compared with single BRAF inhibitor alone in melanoma patients. Appropriate prevention and management are recommended.
Collapse
Affiliation(s)
- Peng Chen
- a Department of Pharmacy , Renmin Hospital of Wuhan University , Wuhan , Hubei , P.R. China
| | - Fucaho Chen
- b Department of Pharmacy , Dongfeng Hospital, Hubei University of Medicine , Shiyan , Hubei , P.R. China
| | - Benhong Zhou
- a Department of Pharmacy , Renmin Hospital of Wuhan University , Wuhan , Hubei , P.R. China.,c School of Pharmaceutical Sciences , Wuhan University , Wuhan , Hubei , P.R. China
| |
Collapse
|
|
30
|
Rao SN, Cabanillas ME. Navigating Systemic Therapy in Advanced Thyroid Carcinoma: From Standard of Care to Personalized Therapy and Beyond. J Endocr Soc 2018; 2:1109-1130. [PMID: 30250937 PMCID: PMC6141902 DOI: 10.1210/js.2018-00180] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Accepted: 08/08/2018] [Indexed: 12/13/2022] Open
Abstract
Thyroid cancer, with the exception of anaplastic thyroid cancer, typically has very favorable outcomes with the standard therapy. However, those that persist, recur, or metastasize are associated with a worse prognosis. Targeted therapy with kinase inhibitors has shown promise in advanced cases of thyroid cancer, and currently five drug regimens are approved for use in clinical practice in the treatment of differentiated, medullary, and anaplastic thyroid cancer, with more options in the pipeline. However, one of the greatest dilemmas is when and how to initiate one of these drugs, and this is discussed herein.
Collapse
Affiliation(s)
- Sarika N Rao
- MedStar Washington Hospital Center, Washington, DC
- Georgetown University School of Medicine, Washington, DC
| | | |
Collapse
|
|
31
|
Ravasco J, Lebaud P, Bodin H. Papulopustular lesions of the face caused by panitumumab: case report and literature review. JOURNAL OF ORAL MEDICINE AND ORAL SURGERY 2018. [DOI: 10.1051/mbcb/2017033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Introduction:Panitumumab (VECTIBIX®) is a monoclonal antibody used alone or in combination with a chemotherapy for management of metastatic colorectal cancer.Observation:A patient treated with this protocol manifested skin lesions; the etiological diagnosis was difficult. The lesions, namely a papulopustular rash at the lower third of the face, and the medical history allowed to diagnose an acute skin toxicity case due to this monoclonal antibody.Commentary:Many side effects are related to the panitumumab, among which dermatologic adverse events having already been the subject of some publications. Nevertheless, several studies conclude that the therapeutic benefit of this epidermal growth factor receptor inhibitor makes acceptable these complications.Conclusion:Stop treatment and corticosteroids allowed a whole and quick disappearance of skin lesions. Alongside dermatologists and infectious diseases specialists, the opinion of an oral surgeon was useful to provide an answer to these symptoms.
Collapse
|
|
32
|
Aguilar-Company J, Fernández-Ruiz M, García-Campelo R, Garrido-Castro AC, Ruiz-Camps I. 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). Clin Microbiol Infect 2018; 24 Suppl 2:S41-S52. [PMID: 29426804 DOI: 10.1016/j.cmi.2017.12.027] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2017] [Revised: 12/18/2017] [Accepted: 12/30/2017] [Indexed: 12/14/2022]
Abstract
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.
Collapse
Affiliation(s)
- J Aguilar-Company
- Departments of Infectious Diseases and Oncology, University Hospital Vall d'Hebron, Autonomous University of Barcelona, Barcelona, Spain
| | - M Fernández-Ruiz
- Unit of Infectious Diseases, Hospital Universitario '12 de Octubre', Instituto de Investigación Hospital '12 de Octubre' (i + 12), School of Medicine, Universidad Complutense, Madrid, Spain; Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain
| | - R García-Campelo
- Department of Medical Oncology, Complejo Hospitalario Universitario A Coruña, A Coruña, Spain
| | - A C Garrido-Castro
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
| | - I Ruiz-Camps
- Department of Infectious Diseases, University Hospital Vall d'Hebron, Autonomous University of Barcelona, Barcelona, Spain; Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain.
| |
Collapse
|
|
33
|
Wei F, Shin D, Cai X. Incidence, risk and prognostic role of anti-epidermal growth factor receptor-induced skin rash in biliary cancer: a meta-analysis. Int J Clin Oncol 2017; 23:443-451. [PMID: 29289981 DOI: 10.1007/s10147-017-1231-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Accepted: 12/20/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Anti-epidermal growth factor receptor (EGFR)-induced skin rash is a common adverse event and is considered a prognostic factor of various cancers. However, the role of rash is rarely known in biliary cancer, possibly owing to the low incidence of this frequently fatal malignancy. We thus performed a meta-analysis to investigate the incidence, risk and prognostic significance of skin rash related to anti-EGFR treatment for biliary cancer. METHODS Eligible studies were enrolled after a systematic search of electronic databases. A fixed-effects or random-effects model was utilized according to the heterogeneity. RESULTS Fourteen clinical trials published between 2006 and 2017 comprising 1,106 patients with advanced biliary cancer were included. The overall incidence of all-grade and high-grade (grade ≥3) rash was 78.2% [95% confidence interval (CI) 70.4-84.3] and 11.3% (7.6-16.5), respectively. Anti-EGFR treatment correlates with a significantly increased risk of all-grade [risk ratio (RR) 7.37, 95% CI 5.11-10.64, p < 0.0001] and high-grade (RR 6.94, 95% CI 1.89-25.45, p = 0.0035) rash compared with control medication. Higher grades of skin rash correlate with a higher objective response rate (RR 3.50, 95% CI 1.47-8.33, p = 0.0048), and a longer overall [hazard ratio (HR) 0.47, 95% CI 0.31-0.71, p = 0.0003) and progression-free survival (HR 0.51, 95% CI 0.36-0.72, p = 0.0001) compared with lower grades or no rash in patients who received anti-EGFR treatment. CONCLUSIONS Anti-EGFR treatment correlates with an increased risk of skin rash in advanced biliary cancer. Stratifying patients by the severity of rash may have major implications for survival benefit regarding anti-EGFR treatment for biliary cancer.
Collapse
Affiliation(s)
- Fangqiang Wei
- Department of General Surgery, Institute of Minimally Invasive Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, No. 3, Qingchun Road, Hangzhou, 310016, Zhejiang, China.,Department of Developmental Biology, Pittsburgh Liver Research Center, McGowan Institute for Regenerative Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15260, USA
| | - Donghun Shin
- Department of Developmental Biology, Pittsburgh Liver Research Center, McGowan Institute for Regenerative Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15260, USA
| | - Xiujun Cai
- Department of General Surgery, Institute of Minimally Invasive Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, No. 3, Qingchun Road, Hangzhou, 310016, Zhejiang, China.
| |
Collapse
|
|
34
|
van Doorn R, van Zuuren EJ. Epidermal growth factor receptor inhibitor-associated rash prevented by oral tetracyclines. Br J Dermatol 2017; 175:1135-1136. [PMID: 27996150 DOI: 10.1111/bjd.15033] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Affiliation(s)
- R van Doorn
- Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands
| | - E J van Zuuren
- Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands
| |
Collapse
|
|
35
|
Arora N, Gupta A, Singh PP. Biological agents in gastrointestinal cancers: adverse effects and their management. J Gastrointest Oncol 2017; 8:485-498. [PMID: 28736636 DOI: 10.21037/jgo.2017.01.07] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Biological therapy comprises agents that by virtue of their unique mechanisms of action, are able to specifically incite a response against or target malignant cells. They differ from conventional chemotherapy with regard to mechanisms of action, indications and side effect profile. Biologic agents have revolutionized therapy for a number of malignancies. In the setting of gastrointestinal (GI) malignancies, agents targeting vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (Her2/Neu) and epidermal growth factor receptor (EGFR) have proven to be invaluable additions to chemotherapy. However, these agents bring with them a set of side effects attributable to their unique mechanisms of action. The anti VEGF agents-bevacizumab, aflibercept and ramucirumab, can result in renal and vascular complications such as hypertension, arterial thrombotic events (ATE), proteinuria and GI perforations. The anti EGFR agents classically cause dermatological toxicities, in addition to hypomagnesemia, which can be dose limiting for patients. Trastuzumab, a monoclonal antibody that targets Her2/Neu, is known to cause cardiotoxicity, especially when used with anthracyclines. Use of immunotherapy agents such as nivolumab is associated with the development immune related adverse events (irAEs). The use of these agents is expected to increase over the next few years and it is crucial that patients and practitioners are aware of their adverse effects and current management strategies. This review highlights the adverse events associated with the use of biologic and immunologic therapies in GI cancers, their incidence and current management strategies.
Collapse
Affiliation(s)
- Nivedita Arora
- Department of Internal Medicine, University of Texas Southwestern Medical Centre, Dallas, TX, USA
| | - Arjun Gupta
- Department of Internal Medicine, University of Texas Southwestern Medical Centre, Dallas, TX, USA
| | - Preet Paul Singh
- Division of Hematology/Oncology, Springfield Clinic Cancer Center, Springfield, Illinois, USA
| |
Collapse
|
|
36
|
Venniyoor A, Al Bahrani B. Minocycline Improves the Efficacy of EGFR Inhibitor Therapy: A Hypothesis. Front Oncol 2016; 6:231. [PMID: 27833902 PMCID: PMC5081343 DOI: 10.3389/fonc.2016.00231] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2016] [Accepted: 10/13/2016] [Indexed: 11/13/2022] Open
Abstract
Skin rash is a side effect of drugs that inhibit epithelial growth factor receptor (EGFR) as a part of targeted therapy of cancer. Its appearance and severity correlates with survival. Minocycline, an oral tetracycline antibiotic, is recommended as treatment (and increasingly, for prevention) of the rash, though infection is seen in only one-third of the patients. Minocycline has additional anticancer properties such as poly(ADP-ribose) polymerase inhibition. It is proposed that such properties contribute to the efficacy of EGFR inhibitors and can also explain the positive correlation between grade of rash and survival as patients with higher grades of rash are more likely to receive minocycline. Early concurrent administration of minocycline is recommended in patients planned for EGFR therapy while awaiting trials proving this hypothesis.
Collapse
Affiliation(s)
- Ajit Venniyoor
- National Oncology Center, The Royal Hospital , Muscat , Oman
| | | |
Collapse
|
|
37
|
Petrelli F, Borgonovo K, Barni S. Preventing or treating anti-EGFR related skin rash with antibiotics? ANNALS OF TRANSLATIONAL MEDICINE 2016; 4:312. [PMID: 27668232 DOI: 10.21037/atm.2016.07.01] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Fausto Petrelli
- ASST Bergamo Ovest, Medical Oncology Unit, Treviglio (BG), Italy
| | - Karen Borgonovo
- ASST Bergamo Ovest, Medical Oncology Unit, Treviglio (BG), Italy
| | - Sandro Barni
- ASST Bergamo Ovest, Medical Oncology Unit, Treviglio (BG), Italy
| |
Collapse
|