ReviewGrading dermatologic adverse events of cancer treatments: The Common Terminology Criteria for Adverse Events Version 4.0
Section snippets
CTCAE version 4.0
The CTCAE is a descriptive terminology that has been widely used for AE reporting. The purpose of the CTCAE is to provide standards for the description and exchange of drug safety information in the treatment of patients with cancer. The CTCAE lists AE terms based on signs, symptoms, or abnormal diagnostic test results seen in oncology interventions.6 Each AE term is associated with a 5-point grading scale to measure the severity of clinical presentations. The grading scale provides uniformity
Medical dictionary for regulatory activities (MedDRA)
The MedDRA, developed by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), is a clinically validated dictionary used internationally by regulatory authorities and the biopharmaceutical industry throughout the entire regulatory process, from premarketing to postmarketing activities, for data entry, retrieval, evaluation, and presentation. The MedDRA dictionary is organized by System Organ Class (SOC) divided into
CTCAE grade scale
The importance of CTCAE is from its grading system and focus on AEs seen in oncology therapeutic trials. MedDRA is a medical terms list that does not provide a grading scale, nor does it differentiate between normal events (puberty) and adverse drug reactions (skin rash). A serious AE is defined as any medical event that is life threatening or fatal after exposure to medical treatment. The term “life threatening” in the definition of “serious” refers to a situation where the patient was at risk
Attribution
An attribution is an assessment of whether an AE is likely caused by the agent(s) being used. When determining if an AE is related to a medical treatment or procedure, the following attribution categories are used by the CTCAE for assessment of AEs: “definite,” “probable,” “possible,” “unlikely,” and “unrelated” (Table II). This has an impact on subsequent treatment of the patients.
SOC and adverse events
In CTCAE v4.0, AEs are grouped by MedDRA Primary SOC. The SOCs are the highest level of the MedDRA hierarchy and are identified by system, etiology, or purpose. There are 26 SOCs in the CTCAE v4.0. Within each SOC, AEs are listed and accompanied by descriptions of severity (grade). In addition, each SOC provides an AE for “Other, specify,” which allows the physician to describe an AE not listed with the general grading system of Table I. The majority of dermatologic-related AEs are found in the
Hair changes (alopecia, hirsutism, and hypertrichosis)
Hair changes are AEs associated with psychosocial impact. Alopecia was the most common dermatologic AE seen with cancer therapy before the use of targeted therapies. In a review by Koo et al,10 treatments with the highest incidence of complete alopecia included the following: epirubicin + paclitaxel (100%), doxorubicin + cyclophosphamide (50%-96%), epirubicin + verapamil (75%), docetaxel (74%), and doxorubicin (61%-70%). Only AS101 and minoxidil have been shown to reduce the severity or shorten
Dermatologic AE listed under other SOCs
CTCAE version 4.0 organizes the AE terms under their placement in MedDRA SOC. Some skin conditions are placed in other SOCs, such as “Infections and infestations” and “Injury, poisoning and procedural complications” (Table IV). Some examples include dermatitis radiation, radiation recall reaction, paronychia, rash pustular, and skin infection.
Conclusion
New targeted cancer therapies have resulted in new dermatologic AEs not seen with conventional chemotherapeutic agents. Recently, the MASCC Skin Toxicity Study Group published a proposed EGFR inhibitor dermatologic AE-specific grading scale.9 This system was used to guide the revision of dermatologic AEs listed in the CTCAE v4.0. The working groups took into consideration the impact on clinical management, changes in dose, or withdrawal of agents. Significant attention was focused on the
References (35)
- et al.
Dermatologic challenges in cancer patients and survivors
Oncology
(2007) - et al.
Dermatologic infections in cancer patients treated with epidermal growth factor receptor inhibitor therapy
J Natl Cancer Inst
(2010) - et al.
Effects of epidermal growth factor receptor inhibitor-induced dermatologic toxicities on quality of life
Cancer
(2010) - et al.
The emergence of supportive oncodermatology: the study of dermatologic adverse events to cancer therapies
J Am Acad Dermatol
(2011) - et al.
Efficacy and skin toxicity management with cetuximab in metastatic colorectal cancer: outcomes from an oncologic/dermatologic cooperation
Clin Colorectal Cancer
(2008) - et al.
CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment
Semin Radiat Oncol
(2003) - NCI. CTCAE. Available from: URL:http://evs.nci.nih.gov/ftp1/CTCAE/About.html. Accessed May, 17,...
- ICH harmonized tripartite guideline post-approval safety data management: definitions and standards for expedited...
- et al.
A proposed EGFR inhibitor dermatologic adverse event-specific grading scale from the MASCC skin toxicity study group
Support Care Cancer
(2010) - et al.
Incidence of chemotherapy-induced alopecia by chemotherapy regimen: a review of published randomized trials
Proc Am Soc Clin Oncol
(2002)
Protection against chemotherapy-induced alopecia
Pharm Res
Chapter 146, Cutaneous lymphoma
Clinical presentation and pathophysiology of EGFRI dermatologic toxicities
Oncology (Williston Park)
Nail toxicity induced by cancer chemotherapy
J Oncol Pharm Pract
Taxane-induced nail changes: incidence, clinical presentation and outcome
Ann Oncol
Cutaneous side-effects of kinase inhibitors and blocking antibodies
Lancet Oncol
The hand-foot syndrome–a frequent secondary manifestation in antineoplastic chemotherapy
Eur J Dermatol
Supported by US National Institutes of Health; Dr Lacouture receives funding from a Zell Scholarship from the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and a Dermatology Foundation Career Development Award.
Disclosure: Dr Cotliar serves on an advisory board for Amgen. Dr Anadkat is a speaker and consultant for ImClone and BMS; and a speaker for Genentech, Eisai, and Hana Biosciences. Dr Lacouture has worked as a consultant for ImClone, Bristol-Myers Squibb, GSK, Amgen, Merck, Vertex, Roche, Pfizer, OSI Pharmaceuticals Inc, and Genentech. Dr Chen, Ms Setser, Dr Olsen, and Mr Garden have no conflicts of interest to declare.
Reprints not available from the authors.