Prospective practice survey of management of cetuximab-related skin reactions.

PURPOSE: Evidence-based guidelines on how to prevent or treat cetuximab-related skin reactions are lacking and multiple care and management strategies are used. The main purpose of the present study is to gain information about the different skincare products being used against skin reactions in metastatic colorectal cancer (mCRC) and recurrent/metastatic (R/M) or locally advanced (LA) squamous cell cancer of the head and neck (SCCHN) patients treated with cetuximab. METHODS: An open-label, prospective observational study conducted in the Netherlands. The occurrence of skin reactions and the care and management options taken were documented for 16 weeks, starting from the first administration of cetuximab. RESULTS: A total of 103 patients were included in 7 hospitals. 38 patients (37%) developed a grade ≥ 2 skin reaction. Eighty-six patients could be analysed for the primary endpoint (73.3% males, mean age 62.4 years, n = 44 LA SCCHN, n = 16 R/M SCCHN, n = 26 mCRC). The most frequently used skin products at some point during the observation period were moisturizing products (70%), systemic antibiotics (64%), topical antibiotics (58%), lipid-regenerating (28%) and other topical products (28%). The overall use of products gradually increased from baseline to week 6-10, reducing by week 16. Hospital protocols were the primary reason (> 50%) for choice of the skincare products and medications. CONCLUSION: A variety of skin care products and antibiotics were commonly used. Only few patients developed severe cutaneous reactions. For patients, the occurrence of skin reactions did not influence their willingness to continue cetuximab therapy.

Patient-reported outcome measures in a pharmacokinetic study with sunitinib, a prospective cohort study.

PURPOSE: During treatment with tyrosine kinase inhibitors, such as sunitinib, patients experience treatment and/or disease-related symptoms. Although application of patient-reported outcome measures (PROMs) enhances early recognition of symptoms, early clinical trials are focused on symptom severity objectified by the Common Terminology Criteria for Adverse Events (CTCAE) in order to evaluate drug safety and to determine a personalized and/or safe dosage range. To gain insight into patient-reported symptoms in addition to healthcare professional-reported adverse events (AEs), a substudy was conducted in an ongoing pharmacokinetic-guided sunitinib dosing study. METHODS: In patients for whom sunitinib was considered standard therapy or patients with advanced/metastatic tumors for whom no standard therapy was available, patient-reported symptoms and well-being besides healthcare professional-reported AEs were assessed. RESULTS: Twenty-nine patients were included for analysis. Over 50% of them experienced a decreased well-being, caused by symptoms of mild and moderate intensity. Compared to healthcare professionals, all measured symptoms, with the exception of fatigue and vomiting, were reported statistically significantly more often by patients. CONCLUSIONS: Application of PROMs in early clinical trials on personalized or individualized oral targeted anticancer agents is feasible and enhances early recognition of symptom burden due to multiple CTCAE grade 1-2 AEs, just as pro-active symptom management and effect evaluation of interventions performed. Application of PROMs in these trials might be clinically relevant in obtaining dose-limiting toxicities.

Patient-reported symptoms and stepwise symptom management in patients on epidermal growth factor inhibitors: A retrospective, descriptive cohort study.

Adverse events (AEs) of epidermal growth factor inhibitors (EGFRi) influence well-being with a risk to dose modifications (DMs). Hereby, clinical benefit of treatment might be affected. This retrospective cohort study was set up to gain insight into the suitability and added value of a patient-reported outcome measurement tool (PROM), together with a stepwise intervention management plan for EGFRi-related AEs in daily practice. The primary objective was to gain insight into total treatment duration and DMs, and the secondary objective to gain insight into patient-reported symptoms and well-being as well as healthcare professional-reported AEs. Sixty-eight patients on cetuximab and 19 on panitumumab treatment were included for analysis; 69% had squamous cell carcinoma of head and neck (SCCHN) and 26% metastatic colorectal carcinoma. DMs due to AEs occurred in 39% of the patients and dose discontinuations in 22%. Especially anorexia, dysphagia, oral pain and skin changes led to a decreased well-being. In patients on EGFRi, application of PROMs together with a stepwise symptom management plan enhances early recognition of symptom burden, pro-active symptom management and effect evaluation of interventions performed whereby well-being recovers. Since only SCCHN patients discontinued treatment due to AEs, patient-centred care focused on radiotherapy-related AEs, creates opportunities for amelioration.

Symptoms from treatment with sunitinib or sorafenib: a multicenter explorative cohort study to explore the influence of patient-reported outcomes on therapy decisions.

PURPOSE: Optimal long-lasting treatment with sunitinib and sorafenib is limited by dose modifications (DMs) due to adverse events (AEs). These AEs may be underrecognized and their influence on health-related quality of life (HRQL) underestimated. Improved insight into the relationship between AEs and therapy decisions is needed. To improve decision making around managing symptoms and reduce DMs, this study was set up to explore the influence of patient-reported symptoms on therapy decisions. METHODS: In this multicenter cohort study, patient characteristics, reasons for and different forms of used dose modifications, and AEs were prospectively obtained from cancer patients on sunitinib/sorafenib treatment. Used instruments to get insight into AEs were the patient-scored Utrecht Symptom Diary (USD) and the professional-scored Common Terminology Criteria for AEs version 3.0. RESULTS: Median total treatment duration in 42 patients was 16 weeks. Median time till dose modification was 10 weeks. DMs occurred mostly due to multiple mild AEs. By using the USD, a higher prevalence of most AEs was found compared to the literature. Sixty percent of the patients experienced a decreased HRQL due to multiple AEs. CONCLUSIONS: Because severe AEs due to sunitinib/sorafenib treatment seldom occur, it is more important to focus on treating and preventing multiple mild AEs with higher impact on HRQL, when trying to avoid dose modifications. Using patient self-reported measurement methods helps to early recognize symptoms and to differentiate among symptom intensities. This systematic approach might help to achieve the optimal dosing, which might improve PFS and OS.

[Skin eruptions as an adverse reaction to epidermal growth-factor receptor inhibitors]. / Huidafwijkingen als bijwerking van remmers van epidermale-groeifactorreceptor.

Inhibition of the epidermal growth-factor receptor (EGFR) is a new strategy in the treatment of solid malignancies. Two men, aged 65 and 59 years, with a metastasized renal carcinoma and a 51-year-old man with a metastasized melanoma developed an acneiform eruption during EGFR inhibition. The second and third patient also developed paronychia. Treatment in all patients consisted of antiseptics and topical antibiotics; the first and third patient also received an oral antibiotic. Withdrawal of the EGFR inhibitor because of progression of the disease led to complete recovery of the cutaneous lesions in the first and the third patient; both died after several months. In the second patient, the side effects reached an acceptable level during continued EGFR therapy. EGFR inhibition is usually accompanied by cutaneous side effects. An acneiform eruption is seen in up to 90% of all treated patients. Other side effects include dry skin, and nail and hair changes. The pathogenesis of these side effects is related to inhibition of EGFR signalling pathways in the skin, but is not yet fully understood. The treatment of EGFR inhibitor-mediated cutaneous toxicity is based mainly on clinical experience.