Joel B. Epstein

Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review

BACKGROUND AND PURPOSE To determine the frequency of mucositis and associated outcomes in patients receiving radiotherapy (RT) for head and neck cancer through a systematic review of recently published literature. MATERIALS AND METHODS According to the study protocol, databases were searched for randomized clinical trials (English only, 1996-1999) of patients with head and neck cancer receiving RT with or without chemotherapy that reported one or more outcomes of interest. RESULTS Thirty-three studies (n=6181 patients) met inclusion criteria. Mucositis was defined using a variety of scoring systems. The mean incidence was 80%. Over one-half of patients (56%) who received altered fractionation RT (RT-AF) experienced severe mucositis (grades 3-4) compared to 34% of patients who received conventional RT. Rates of hospitalization due to mucositis, reported in three studies (n=700), were 16% overall and 32% for RT-AF patients. Eleven percent of patients had RT regimens interrupted or modified because of mucositis in five studies (n=1267) reporting this outcome. Data insufficiency or heterogeneity prohibited analysis of mucositis severity and other associated outcomes, such as oral pain, dysphagia and opioid use. CONCLUSIONS Mucositis is a frequent, severe toxicity in patients treated with RT for head and neck cancer. While it appears that mucositis may lead to hospitalization and treatment interruptions, its overall impact on outcomes has not been adequately investigated.

Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis.

Oral and gastrointestinal (GI) mucositis can affect up to 100% of patients undergoing high‐dose chemotherapy and hematopoietic stem cell transplantation, 80% of patients with malignancies of the head and neck receiving radiotherapy, and a wide range of patients receiving chemotherapy. Alimentary track mucositis increases mortality and morbidity and contributes to rising health care costs. Consequently, the Multinational Association of Supportive Care in Cancer and the International Society for Oral Oncology assembled an expert panel to evaluate the literature and to create evidence‐based guidelines for preventing, evaluating, and treating mucositis.

Updated clinical practice guidelines for the prevention and treatment of mucositis

Considerable progress in research and clinical application has been made since the original guidelines for managing mucositis in cancer patients were published in 2004, and the first active drug for the prevention and treatment of this condition has been approved by the United States Food and Drug Administration and other regulatory agencies in Europe and Australia. These changes necessitate an updated review of the literature and guidelines. Panel members reviewed the biomedical literature on mucositis published in English between January 2002 and May 2005 and reached a consensus based on the criteria of the American Society of Clinical Oncology. Changes in the guidelines included recommendations for the use of palifermin for oral mucositis associated with stem cell transplantation, amifostine for radiation proctitis, and cryotherapy for mucositis associated with high‐dose melphalan. Recommendations against specific practices were introduced: Systemic glutamine was not recommended for the prevention of gastrointestinal mucositis, and sucralfate and antimicrobial lozenges were not recommended for radiation‐induced oral mucositis. Furthermore, new guidelines suggested that granulocyte–macrophage‐colony stimulating factor mouthwashes not be used for oral mucositis prevention in the transplantation population. Advances in mucositis treatment and research have been complemented by an increased rate of publication on mucosal injury in cancer. However, additional and sustained efforts will be required to gain a fuller understanding of the pathobiology, impact on overall patient status, optimal therapeutic strategies, and improved educational programs for health professionals, patients, and caregivers. These efforts are likely to have significant clinical and economic impact on the treatment of cancer patients. Cancer 2007;109:820–31.

Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities

BackgroundEpidermal growth factor receptor inhibitors (EGFRI) produce various dermatologic side effects in the majority of patients, and guidelines are crucial for the prevention and treatment of these untoward events. The purpose of this panel was to develop evidence-based recommendations for EGFRI-associated dermatologic toxicities.MethodsA multinational, interdisciplinary panel of experts in supportive care in cancer reviewed pertinent studies using established criteria in order to develop first-generation recommendations for EGFRI-associated dermatologic toxicities.ResultsProphylactic and reactive recommendations for papulopustular (acneiform) rash, hair changes, radiation dermatitis, pruritus, mucositis, xerosis/fissures, and paronychia are presented, as well as general dermatologic recommendations when possible.ConclusionPrevention and management of EGFRI-related dermatologic toxicities is critical to maintain patients’ health-related quality of life and dose intensity of antineoplastic regimens. More rigorous investigation of these toxicities is warranted to improve preventive and treatment strategies.

Benzydamine HCl for prophylaxis of radiation-induced oral mucositis

Benzydamine was evaluated in patients with head and neck carcinoma for treatment of radiation‐induced oral mucositis, a frequent complication of radiation therapy (RT) for which there is no predictable therapy or preventive treatment currently available.

Taste and smell dysfunction in patients receiving chemotherapy: a review of current knowledge.

Abstract. Disorders of taste are prevalent in patients undergoing chemotherapy and often have a negative impact on quality of life and nutrition. We now present a review of the physiology of taste and smell and a discussion of the multiple causes of disturbances in these senses in patients undergoing standard- and high-dose chemotherapy. A better understanding of the complex and often multifactorial etiology of taste dysfunction should enable the clinician to institute measures to minimize the impact of these disturbing changes.

Oral lichen planus: Progress in understanding its malignant potential and the implications for clinical management

Oral lichen planus (OLP) is an inflammatory lesion that has malignant potential, but few cases of OLP progress to malignancy. A diagnosis of OLP should be confirmed on the basis of historical, clinical, and histologic data. The presence of dysplasia in an OLP-like lesion increases the risk of malignant transformation, mandating management and close follow-up. A molecular assessment of OLP may provide the best evidence of malignant risk and will likely become available for clinical use. In addition, exfoliated cells may be examined for loss of heterozygosity and may become a valuable clinical tool for patient follow-up. The treatment of OLP should include elimination of tissue irritants and recurring exposure to oral carcinogens. If OLP is symptomatic, appropriate treatment with immunosuppressive medications, particularly corticosteroids, should be undertaken. For lesions with dysplastic changes, management may include attention directed to the inflammatory change and follow-up biopsies to assess residual histologic changes that may represent dysplasia. Dysplastic OLP may be best treated as other oral dysplastic conditions; thus, regular, more frequent follow-up is required.

A proposed EGFR inhibitor dermatologic adverse event-specific grading scale from the MASCC skin toxicity study group

BackgroundAccurate grading of dermatologic adverse events (AE) due to epidermal growth factor receptor (EGFR) inhibitors (EGFRIs) is necessary for drug toxicity determinations, interagent comparisons, and supportive care trials. The most widely used severity grading scale, the National Cancer Institute’s Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE v4.0), was not designed specifically for this class of agents and may result in underreporting and poor grading of distinctive adverse events. We believe a class-specific grading scale is needed to help standardize assessment and improve reporting of EGFRI-associated dermatologic AEs.MethodsThe Multinational Association of Supportive Care in Cancer (MASCC) Skin Toxicity Study Group conducted an international multidisciplinary meeting that included 20 clinicians and researchers from academic centers and government agencies. Experts from different disciplines presented current information specific to EGFRI-induced dermatologic toxicities: grading scale development, pharmacovigilance safety reporting, health-related quality of life, patient reporting, and pharmacology. Group discussions, literature reviews, and professional expertise established the theoretical foundation for the proposed grading scale.ResultsA new grading system is proposed for the most common events associated with EGFRI-induced dermatologic AEs: papulopustular reaction or acneiform rash, nail changes, erythema, pruritus, xerosis, hair changes, telangiectasias, hyperpigmentation, mucositis, flushing, radiation dermatitis, hyposalivation, and taste changes. The proposed scale maintains consistency with the grading principles and language of the existing CTCAE version 4.0 and MedDRA terminology and includes relevant patient-reported health-related quality of life factors.ConclusionsA grading scale specific to EGFR inhibitor dermatologic AEs is presented for formal integration into future versions of CTCAE and for validation in clinical trial settings. The study group designed this scale to detect and report EGFRI-related toxicities with greater sensitivity, specificity, and range than the scales currently used. This scale should serve as a foundation for efforts to perform objective interdrug comparisons and assessments of supportive care treatment strategies more effectively than with current methods.

Oral mucositis: A challenging complication of radiotherapy, chemotherapy, and radiochemotherapy. Part 2: Diagnosis and management of mucositis

Oral mucositis is a common sequel of radiotherapy, chemotherapy, and radiochemotherapy in patients with cancer or patients requiring hemopoietic stem cell transplants. Mucositis has a direct and significant impact on the duration of disease remission and cure rates, because it is a treatment‐limiting toxicity. Mucositis also affects survival because of the risk of infection and has a significant impact on quality of life and cost of care.

Carcinogenesis and cyclooxygenase: the potential role of COX-2 inhibition in upper aerodigestive tract cancer.

Cyclooxygenase-2 (COX-2) is upregulated in a number of epithelial cancers, including in upper aerodigestive tract (UADT) premalignant and malignant lesions. The purpose of this review is to provide a comprehensive examination of the potential of COX-2 inhibition in prevention of UADT premalignant and malignant disease. A Medline and Cancerlit literature search was conducted for the period 1993-2002, and identified literature was reviewed. There is evidence from in vitro studies, as well as animal models, that inhibition of COX-2 may suppress carcinogenesis by affecting a number of pathways of carcinogenesis, promoting apoptosis and inhibiting angiogenesis. Preliminary studies of gastro-intestinal (GI) carcinogenesis suggest that COX-2 inhibitors may represent an approach to the chemoprevention of epithelial cancers. COX-2 inhibitors may have a potential role in chemoprevention of UADT cancer, and clinical trials appear warranted.