Management of Skin Reactions During Cetuximab Treatment in Association With Chemotherapy or Radiotherapy Update of the Italian Expert Recommendations

Objectives: Cetuximab was shown in phase III clinical trials to improve chemotherapy efficacy in patients with advanced colorectal and head-neck cancer. Appropriate management of skin reactions associated with epidermal growth factor receptor inhibitor therapy is necessary to allow adequate drug compliance and to improve patient quality of life and outcomes. Methods: The RAND/UCLA Appropriateness Method was used by a group of experts to produce new Italian recommendations on the management of skin reactions in this setting. Statements were generated on the basis of an updated systematic review of the literature and rated twice by a panel of 38 expert physicians. A meeting of the panel was held after the first rating session. Results: Skin reactions included acneiformic rash, skin dryness (xerosis), pruritus, paronychia, hair abnormalities, mucositis, and increased growth of eyelashes or facial hair. Updates of the previous recommendations on the prevention and treatment of each type of reaction were proposed. Conclusions: This updated Expert Opinion focuses on how to assess and correctly grade skin reactions according to the latest National Cancer Institute Common Terminology Criteria for Adverse Events and on how to manage these adverse events in clinical practic

Management of Skin Reactions During Cetuximab Treatment in Association With Chemotherapy or Radiotherapy: Update of the Italian Expert Recommendations

Objectives: Cetuximab was shown in phase III clinical trials to improve chemotherapy efficacy in patients with advanced colorectal and head-neck cancer. Appropriate management of skin reactions associated with epidermal growth factor receptor inhibitor therapy is necessary to allow adequate drug compliance and to improve patient quality of life and outcomes. Methods: The RAND/UCLA Appropriateness Method was used by a group of experts to produce new Italian recommendations on the management of skin reactions in this setting. Statements were generated on the basis of an updated systematic review of the literature and rated twice by a panel of 38 expert physicians. A meeting of the panel was held after the first rating session. Results: Skin reactions included acneiformic rash, skin dryness (xerosis), pruritus, paronychia, hair abnormalities, mucositis, and increased growth of eyelashes or facial hair. Updates of the previous recommendations on the prevention and treatment of each type of reaction were proposed. Conclusions: This updated Expert Opinion focuses on how to assess and correctly grade skin reactions according to the latest National Cancer Institute Common Terminology Criteria for Adverse Events and on how to manage these adverse events in clinical practice

Activation of immune responses in patients with relapsed-metastatic head and neck cancer (CONFRONT phase I-II trial): Multimodality immunotherapy with avelumab, short-course radiotherapy, and cyclophosphamide

Introduction and background: Second-line treatment of platinum-resistant relapsed/metastatic (R/M) head and neck cancer (HNC) is a currently unmet clinical need. Clinical trials showed improvement in overall survival and quality of life of R/M-HNC patients treated with anti-PD-1 regardless of the number of prior chemotherapy lines; however, the percentage of long-term survivors remains limited.This study aims to test the hypothesis that attacking the tumor microenvironment at multiple levels can increase immunogenicity of R/M-HNC without worsening the safety profile of immune checkpoint inhibitors. Methods/design: In this open label, multi-center, single-arm, Phase Ib/II, R/M-HNC patients pretreated with at least one line of therapy containing platinum, fluorouracil, and cetuximab will receive a daily metronomic dose of 50 mg cyclophosphamide without a drug-free break, 10 mg/kg avelumab on day 1 and every other week until progression, and a single fraction of 8 Gy radiotherapy on day 8. Discussion: The treatment protocol aims to reverse immune evasion of the tumor through a radiotherapy-induced self-vaccination effect, suppression of CD4+ CD25+ FoxP3+ regulatory T-cell function by metronomic cyclophosphamide, and effector T-cell reactivation owing to the inhibition of the PD-1–PD-L1 axis by avelumab.The immunologic interplay induced by the proposed combined treatment may theoretically improve the activity of avelumab without increasing its toxicity profile.Finally, an ancillary translational study will be extended to all the patients’ population. Trial registration: EudraCT n. 2017-000353-39. Keywords: Head and neck cancer, Avelumab, Cyclophosphamide, Radiotherapy, Clinical trial, Immunotherap

Mucositis in head and neck cancer patients treated with radiotherapy and systemic therapies: Literature review and consensus statements

Background: Oral mucositis (OM) due to radiotherapy and systemic therapies in head and neck cancer treatment represents a major problem causing a wide spectrum of clinical signs and symptoms. This adverse event may reduce quality of life, resulting from debilitating oral pain, bleeding, dysphagia, infections, impairment of food intake, high rate of hospitalization and may interfere with the delivery of programmed treatment plans, ultimately jeopardizing patient outcome. Globally, there is a lack of evidence on effective measures for the prevention and treatment of OM, and only scant uniform conclusions and recommendations can be derived from the existing literature and guidelines. A multidisciplinary team of Italian head and neck cancer experts met in Milan 17-18 February 2013 with the aim of reaching consensus on prophylaxis and management of mucositis. The results of the literature review and the statements that achieved consensus are reported and discussed in this paper. Material and methods: The Delphi Appropriateness Method was used as a structured communication method for achieving consensus. Subsequently, external expert reviewers evaluated the conclusions carefully according to their area of expertise. Results: This paper presents 13 clusters of statements on prophylaxis and treatment of mucositis that achieved consensus. Conclusions: OM represents a very stressful) situation for head and neck cancer patients submitted to chemo-radiation or exclusive radiation treatment. A multidisciplinary approach is mandatory, but there is still no gold-standard protocol that is prominently better than others. (C) 2016 Elsevier Ireland Ltd. All rights reserved

Swallowing dysfunction in head and neck cancer patients treated by radiotherapy: Review and recommendations of the supportive task group of the Italian Association of Radiation Oncology

Purpose: Dysphagia is a debilitating complication in head and neck cancer patients (HNCPs) that may cause a high mortality rate for aspiration pneumonia. The aims of this paper were to summarize the normal swallowing mechanism focusing on its anatomo-physiology, to review the relevant literature in order to identify the main causes of dysphagia in HNCPs and to develop recommendations to be adopted for radiation oncology patients. The chemotherapy and surgery considerations on this topic were reported in recommendations only when they were supposed to increase the adverse effects of radiotherapy on dysphagia. Materials and methods: The review of literature was focused on studies reporting dysphagia as a pre-treatment evaluation and as cancer and cancer therapy related side-effects, respectively. Relevant literature through the primary literature search and by articles identified in references was considered. The members of the group discussed the results and elaborated recommendations according to the Oxford CRBM levels of evidence and recommendations. The recommendations were revised by external Radiation Oncology, Ear Nose and Throat (ENT), Medical Oncology and Speech Language Pathology (SLP) experts. Results: Recommendations on pre-treatment assessment and on patients submitted to radiotherapy were given. The effects of concurrent therapies (i.e. surgery or chemotherapy) were taken into account. Conclusions: In HNCPs treatment, disease control has to be considered in tandem with functional impact on swallowing function. SLPs should be included in a multidisciplinary approach to head and neck cancer. © 2012 Elsevier Ltd

Acute skin toxicity management in head and neck cancer patients treated with radiotherapy and chemotherapy or EGFR inhibitors:Literature review and consensus

The adverse effects of radiation therapy, often integrated with chemotherapy and/or targeted therapies, on the skin include severe acute and chronic dermatitis associated with pain, discomfort, itching, and burning, and may heavily affect patients' quality of life. The management of these skin adverse effects in head and neck cancer patients (HNCPs) are very heterogeneous due to the lack of shared rigorous classification systems and evidence based treatments.A multidisciplinary group of head and neck cancer specialists from Italy met with the aim of reaching a consensus on a clinical definition and management of dermatitis in HNCPs treated with radiotherapy with or without systemic therapies in order to improve skin toxicity management. The Delphi Appropriateness Method was used. External expert reviewers then evaluated the conclusions carefully according to their area of expertise.This paper offers contains seven clusters of statements about the management of dermatitis in HNCPs and a review of recent literature on these topics. (C) 2015 Elsevier Ireland Ltd. All rights reserved.</p

Oral toxicity management in head and neck cancer patients treated with chemotherapy and radiation: Xerostomia and trismus (Part 2). Literature review and consensus statement

Radiotherapy alone or in combination with chemotherapy and/or surgery is a well-known radical treatment for head and neck cancer patients. Nevertheless acute side effects (such as moist desquamation, skin erythema, loss of taste, mucositis etc.) and in particular late toxicities (osteoradionecrosis, xerostomia, trismus, radiation caries etc.) are often debilitating and underestimated. A multidisciplinary group of head and neck cancer specialists from Italy met in Milan with the aim of reaching a consensus on a clinical definition and management of these toxicities. The Delphi Appropriateness method was used for this consensus and external experts evaluated the conclusions. The paper contains 20 clusters of statements about the clinical definition and management of stomatological issues that reached consensus, and offers a review of the literature about these topics. The review was split into two parts: the first part dealt with dental pathologies and osteo-radionecrosis (10 clusters of statements), whereas this second part deals with trismus and xerostomia (10 clusters of statements)

Lactobacillus brevis CD2 for Prevention of Oral Mucositis in Patients With Head and Neck Tumors: A Multicentric Randomized Study

reserved19BACKGROUND: Oropharyngeal mucositis occurs in virtually all patients with head and neck cancer receiving radiochemotherapy. The manipulation of the oral cavity microbiota represents an intriguing and challenging target. PATIENTS AND METHODS: A total of 75 patients were enrolled to receive Lactobacillus brevis CD2 lozenges or oral care regimen with sodium bicarbonate mouthwashes. The primary endpoint was the incidence of grade 3 or 4 oropharyngeal mucositis during radiotherapy treatment. RESULTS: There was no statistical difference in the incidence of grade 3-4 oropharyngeal mucositis between the intervention and control groups (40.6% vs. 41.6% respectively, p=0.974). The incidence of pain, dysphagia, body weight loss and quality of life were not different between the experimental and standard arm. CONCLUSION: Our study was not able to demonstrate the efficacy of L. brevis CD2 lozenges in preventing radiation-induced mucositis in patients with head and neck cancer. Although modulating homeostasis of the salivary microbiota in the oral cavity seems attractive, it clearly needs further study.mixedDE Sanctis, Vitaliana; Belgioia, Liliana; Cante, Domenico; LA Porta, Maria R.; Caspiani, Orietta; Guarnaccia, Roberta; Argenone, Angela; Muto, Paolo; Musio, Daniela; DE Felice, Francesca; Maurizi, Francesca; Bunkhelia, Feisal; Redda, Maria G Ruo; Reali, Alessia; Valeriani, Maurizio; Osti, Mattia F.; Alterio, Daniela; Bacigalupo, Almalina; Russi, Elvio G.DE Sanctis, Vitaliana; Belgioia, Liliana; Cante, Domenico; LA Porta, Maria R.; Caspiani, Orietta; Guarnaccia, Roberta; Argenone, Angela; Muto, Paolo; Musio, Daniela; DE Felice, Francesca; Maurizi, Francesca; Bunkhelia, Feisal; Redda, Maria G Ruo; Reali, Alessia; Valeriani, Maurizio; Osti, Mattia F.; Alterio, Daniela; Bacigalupo, Almalina; Russi, Elvio G