Judith E. Raber-Durlacher

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.

MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy

Mucositis is a highly significant, and sometimes dose‐limiting, toxicity of cancer therapy. The goal of this systematic review was to update the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for mucositis.

Swallowing dysfunction in cancer patients

PurposeDysphagia (swallowing dysfunction) is a debilitating, depressing, and potentially life-threatening complication in cancer patients that is likely underreported. The present paper is aimed to review relevant dysphagia literature between 1990 and 2010 with a focus on assessment tools, prevalence, complications, and impact on quality of life in patients with a variety of different cancers, particularly in those treated with curative chemoradiation for head and neck cancer.MethodsThe literature search was limited to the English language and included both MEDLINE/PubMed and EMBASE. The search focused on papers reporting dysphagia as a side effect of cancer and cancer therapy. We identified relevant literature through the primary literature search and by articles identified in references.ResultsA wide range of assessment tools for dysphagia was identified. Dysphagia is related to a number of factors such as direct impact of the tumor, cancer resection, chemotherapy, and radiotherapy and to newer therapies such as epidermal growth factor receptor inhibitors. Concomitant oral complications such as xerostomia may exacerbate subjective dysphagia. Most literature focuses on head and neck cancer, but dysphagia is also common in other types of cancer.ConclusionsSwallowing impairment is a clinically relevant acute and long-term complication in patients with a wide variety of cancers. More prospective studies on the course of dysphagia and impact on quality of life from baseline to long-term follow-up after various treatment modalities, including targeted therapies, are needed.

Growth factors and cytokines in the prevention and treatment of oral and gastrointestinal mucositis

Goals of workGrowth factors and cytokines may be useful in preventing chemotherapy (CT)- and radiotherapy (RT)-induced oral and gastrointestinal mucositis. Two systematic reviews of the medical literature on growth factors and cytokines for the amelioration of CT- and RT-induced mucositis throughout the alimentary tract were performed by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology. The aim of these evidence-based scientific reviews was to critically evaluate the literature and create evidence-based guidelines for the use of growth factors and cytokines in the prevention or treatment of CT- and RT-induced mucositis.MethodThe two reviews covered articles on clinical trials from January 1966 through May 2002 and preclinical studies from June 2002 through May 2005, respectively. The systematic review process was based on a well-established method for evaluating scientific literature.Main resultsThe number of articles in the first review was 29. In the second review, 23 articles were evaluated, 14 preclinical and 9 clinical studies. It was concluded from the first review that there was no sufficient evidence to provide any recommendations for clinical practice guidelines regarding growth factors and cytokines. From the second review, a guideline could be presented recommending the use of recombinant human keratinocyte growth factor-1 (palifermin) to prevent oral mucositis in patients receiving high-dose CT and total body irradiation followed by stem cell transplantation for haematological malignancies. A guideline could also be provided suggesting that granulocyte macrophage colony-stimulating factor mouthwash not be used for the prevention of oral mucositis in the transplant setting with high-dose CT and autologous or allogeneic stem cell transplantation.ConclusionsThese systematic reviews have provided clarity and shown exciting new results. Further studies will provide new options for this debilitating side-effect of cancer therapy.

Oral Adverse Events Associated with Tyrosine Kinase and Mammalian Target of Rapamycin Inhibitors in Renal Cell Carcinoma: A Structured Literature Review

BACKGROUND Oral adverse events (OAEs) associated with multitargeted tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin inhibitors (mTORIs) are underestimated but frequent and novel presentations of mucosal manifestations. Because optimal antitumor activity requires maintaining the optimal dose, it is essential to avoid unintended treatment delays or interruptions. METHODS We review the reported prevalence and appearance of OAEs with TKIs and mTORIs and the current oral assessment tools commonly used in clinical trials. We discuss the correlations between OAEs and hand-foot skin reaction (HFSR) and rash. RESULTS The reported prevalence of oral mucositis/stomatitis of any grade is 4% for pazopanib, 28% for sorafenib, 38% for sunitinib, 41% for temsirolimus, and 44% for everolimus. Oral lesions associated with these agents have been reported to more closely resemble aphthous stomatitis than OM caused by conventional agents. In addition, these agents may result in symptoms such as oral mucosal pain, dysgeusia, and dysphagia, in the absence of clinical lesions. Because of these factors, OAEs secondary to targeted agents may be underreported. In addition, a correlation between OAEs and HFSR was identified. CONCLUSIONS OAEs caused by TKIs and mTORIs may represent dose-limiting toxicities, especially considering the fact that even low grades of OAEs may be troubling to the patient. We discuss how these novel AEs can be assessed because current mucositis assessment tools have limitations. Prospective studies investigating the pathogenesis, risk factors, and management of OAEs are needed in order to minimize the impact on patients health-related quality of life.

Periodontal infection in cancer patients treated with high-dose chemotherapy

The infected and inflamed periodontium can act as a focus for systemic infection in neutropenic cancer patients. The incidence of these oral infections is unknown, but probably underestimated. Periodontal infections can easily be overlooked, primarily because symptoms of gingival inflammation may be minimal and the infection may be located in deeper parts of the periodontium. Assessment of a patients periodontal condition before the onset of profound neutropenia is critical to the diagnosis and the management of these potentially life-threatening infections. This review article is aimed at informing supportive care providers of recent insights into the pathogenesis of periodontal diseases and the role of subgingival microorganisms, with the emphasis on these infections in cancer patients treated with high-dose chemotherapy. Furthermore, a multidisciplinary approach to the management of periodontal infections and the need for future research is discussed.

Current practice and knowledge of oral care for cancer patients: a survey of supportive health care providers

BackgroundThe Oral Care Study Section of the Multinational Association of Supportive Care in Cancer (MASCC) and the International Society for Oral Oncology (ISOO) conducted a survey on clinical practices of oral/dental management of cancer patients among supportive health care providers. The main purpose was to evaluate the knowledge and current practice for preventing and managing oral side effects associated with intensive chemotherapy (ICT), hematopoietic cell transplant (HCT), and radiation therapy to the head and neck (H&N RT).Materials and methodsA questionnaire designed and pretested was sent to 212 MASCC/ISOO members around the world with different dental and medical backgrounds.Main resultsSeventy-four individuals (35%) responded. The majority of respondents were aware of possible oral complications and provided patients with clinical strategies and recommendations although there was considerable variability among the respondents. Approximately 75% stated that patients were referred for oral/dental care prior to H&N RT and ICT including HCT. However, integrated dental and medical services were reported available in only about 25% of the institutions, and most patients were referred to community-based dental professionals.Main conclusionsThe survey represents a first review of current, international oral care practices. It suggests a need to develop evidence-based clinical guidelines to support effective oral/dental interventions and management strategies for this population. Furthermore, strategies for implementation of oral care protocols and better integration of dental and medical services should be developed. Caution in interpreting these findings is urged due to the limited response rate.

Current practices for management of oral mucositis in cancer patients

Abstract Many anticancer therapies induce oral mucositis, diminishing the patients quality of life. Especially in neutropenic patients, it can lead to life-threatening systemic infection. Moreover, it can become a limiting factor in intensive treatment schedules. Many interventions are aimed at reducing trauma and the risk of secondary infection. The institution of good oral hygiene seems to play a crucial part and can be achieved manually or by means of antiseptic agents. More specific antimicrobial therapy may be indicated. In addition, local and/or systemic pain control may be required. The administration of hematological growth factors, cryoprotectants and other agents or measures that may be of help in the management of mucositis are discussed.

Mammalian target of rapamycin inhibitor-associated stomatitis

With the recent introduction of inhibitors of mammalian target of rapamycin (mTOR) in oncology, distinct cutaneous and oral adverse events have been identified. In fact, stomatitis and rash are documented as the most frequent and potentially dose-limiting side effects. Clinically, mTOR inhibitor-associated stomatitis (mIAS) more closely resembles aphthous stomatitis than oral mucositis due to conventional anticancer therapies. While most cases of mIAS are mild to moderate and self-limiting, more severe and persistent mIAS can become a dose-limiting toxicity. Small ulcerations may cause significant pain and mucosal sensitivity may occur in the absence of clinical changes. Use of clinical assessment tools that are primarily driven by ulceration size may underestimate mIAS, and assessment should include patient-reported outcomes. This article provides an up-to-date review of the clinical presentation, terminology, pathogenesis, assessment and management of mIAS and other mTOR inhibitor-associated oral adverse events. In addition, areas of future research are considered.

Gingival bleeding and jaw bone necrosis in patients with metastatic renal cell carcinoma receiving sunitinib: report of 2 cases with clinical implications

There is emerging evidence that oral mucositis/stomatitis is a common adverse effect of sunitininb antiangiogenic therapy in patients with metastatic renal cell carcinoma (mRCC). In addition, a case of sunitinib-related jaw osteonecrosis was recently described. We report on 2 patients with mRCC treated with sunitinib. The first patient, a 19-year-old woman, treated with cisplatin and sunitinib, presented with oral pain, malodor, spontaneous and continuous gingival bleeding, and painful necrotic ulcerations clinically resembling necrotizing ulcerative gingivitis (NUG). Suntinib-related stomatitis and bleeding were considered cumulative to NUG symptoms. The second patient, a 64-year-old woman, treated with sunitinib only, complained of mandibular pain. Sunitinib-related jaw osteonecrosis was diagnosed. Gingival bleeding and soft tissue necrosis, as well as jaw osteonecrosis may develop as adverse events of sunitinib use. Antiangiogenic therapies are increasingly used in the treatment of cancers. The presented cases are aimed to alert health care professionals on adverse oral events.