Skin Toxicity Evaluation in Patients Treated With Cetuximab for Metastatic Colorectal Cancer: A New Tool for More Accurate Comprehension of Quality of Life Impacts
OncoTargets and Therapy
Objectives: The effectiveness of evaluation of the severity of epidermal growth-factor receptor inhibitor (EGFRI)-associated dermatological toxicities remains a topic of debate. This study was designed to assess the correlation between quality of life (QoL) and severity of dermatological toxicity, evaluated using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) and our novel scale, the Eruption Scoring System (ESS), in metastatic colorectal cancer (CRC) patients treated with first-line chemotherapy combined with cetuximab.
Methods: Cutaneous toxicity was evaluated, by oncologists and dermatologists, in patients (n=30) with histologically confirmed metastatic CRC who were scheduled to begin first-line chemotherapy combined with the EGFRI, cetuximab, using the NCI-CTCAE and ESS tools. Health-related QoL (HRQoL) was evaluated using the Skindex-29 and Skindex-17 dermatology-specific instruments. Correlations between QoL and skin toxicity severity were assessed using Spearman's rank tests. Interclass correlation coefficients were used to assess interoperator agreement for ESS and NCI-CTCAE v4.0 scoring.
Results: A positive correlation was identified between dermatology HRQoL and the severity of dermatological toxicities assessed using the NCI-CTCAE v4.0 scale for cutaneous papulopustular acneiform rash; however, a stronger correlation was observed between HRQoL and toxicities evaluated using the ESS tool. Both NCI-CTCAE v4.0 and ESS tools demonstrated good interobserver agreement for grading of skin toxicity.
Conclusion: There is a strong correlation between the scores generated by the ESS and NCI-CTCAE tools to grade cutaneous toxicity related to treatment with the anti-EGFR monoclonal antibody, cetuximab. ESS can be considered a valid instrument for identification and grading of the severity of skin toxicity induced by cetuximab, with some advantages over the standard NCI-CTCAE scoring system.
Keywords: cetuximab, skin toxicity, EGFRI, colorectal cancer, ESS
Epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor found on cells of epithelial origin, which has an important role in cell differentiation, proliferation, migration, apoptosis, angiogenesis, and cytokine regulation.1–3 EGFR signaling is commonly activated in various solid tumors, including colorectal cancer (CRC), and is associated with tumor progression and poor prognosis.4 Agents targeting EGFR are collectively described as EGFR inhibitors (EGFRIs).
Cetuximab and panitumumab, monoclonal antibody (mAb) EGFRIs, have proved efficient, both as single agents and in combination with chemotherapy, in the treatment of metastatic CRC without mutations in the RAS gene.5–9 The majority of patients treated with EGFR mAbs and also those treated with small molecule inhibitors of the EGFR tyrosine kinase domain, such as gefitinib and erlotinib, experience dermatological side effects.10 EGFR is highly expressed in the epidermis, especially in the basal cell layer, and in the epithelium of hair follicles. Although papulopustular skin rash is the most common skin toxicity associated with anti-EGFR mAbs, other cutaneous side effects are also observed, including xerosis, fissures, pruritus, paronychia, and blepharitis.11,12