StemCell Therapy

Overview

Aggressive treatment of malignant disease may produce unavoidable toxicities to normal cells. The mucosal lining of the gastrointestinal tract, including the oral mucosa, is a prime target for treatment-related toxicity by virtue of its rapid rate of cell turnover. The oral cavity is highly susceptible to direct and indirect toxic effects of cancer chemotherapy and ionizing radiation.[1] This risk results from multiple factors, including high rates of cellular turnover for the lining mucosa, a diverse and complex microflora, and trauma to oral tissues during normal oral function.[2] Although changes in soft tissue structures within the oral cavity presumably reflect the changes that occur throughout the gastrointestinal tract, this summary focuses on oral complications of antineoplastic drugs and radiation therapies.

It is essential that a multidisciplinary approach be used for oral management of the cancer patient before, during, and after cancer treatment. A multidisciplinary approach is warranted because the medical complexity of these patients affects dental treatment planning, prioritization, and timing of dental care. In addition, selected cancer patients (e.g., status posttreatment with high-dose head-and-neck radiation) are often at lifelong risk for serious complications such as osteoradionecrosis of the mandible. Thus, a multidisciplinary oncology team that includes oncologists, oncology nurses, and dental generalists and specialists as well as dental hygienists, social workers, dieticians, and related health professionals can often achieve highly effective preventive and therapeutic outcomes relative to oral complications in these patients.

While oral complications may mimic selected systemic disorders, unique oral toxicities emerge in the context of specific oral anatomic structures and their functions.

Frequencies of oral complications vary by cancer therapy; estimates are included in Table 1.

The most common oral complications related to cancer therapies are mucositis, infection, salivary gland dysfunction, taste dysfunction, and pain. These complications can lead to secondary complications such as dehydration, dysgeusia, and malnutrition. In myelosuppressed cancer patients, the oral cavity can also be a source of systemic infection. Radiation of the head and neck can irreversibly injure oral mucosa, vasculature, muscle, and bone, resulting in xerostomia, rampant dental caries, trismus, soft tissue necrosis, and osteonecrosis.

Severe oral toxicities can compromise delivery of optimal cancer therapy protocols. For example, dose reduction or treatment schedule modifications may be necessary to allow for resolution of oral lesions. In cases of severe oral morbidity, the patient may no longer be able to continue cancer therapy; treatment is then usually discontinued. These disruptions in dosing caused by oral complications can directly affect patient survivorship.

Management of oral complications of cancer therapy includes identification of high-risk populations, patient education, initiation of pretreatment interventions, and timely management of lesions. Assessment of oral status and stabilization of oral disease before cancer therapy are critical to overall patient care. Care should be both preventive and therapeutic to minimize risk for oral and associated systemic complications.

Future research targeted at developing technologies is needed to:

Development of new technologies to prevent cancer therapyinduced complications, especially oral mucositis, could substantially reduce the risk of oral pain, oral and systemic infections, and number of days in the hospital; and could improve quality of life and reduce health care costs. New technologies could also provide a setting in which novel classes of chemotherapeutic drugs, used at increased doses, could lead to enhanced cancer cure rates and durability of disease remission.

As has been noted, it is essential that a multidisciplinary approach be used for oral management of the cancer patient before, during, and after cancer treatment. This collaboration is pivotally important for the advancement of basic, clinical, and translational research associated with oral complications of current and emerging cancer therapies. The pathobiologic complexity of oral complications and the ever-expanding science base of clinical management require this comprehensive interdisciplinary approach.

In this summary, unless otherwise stated, evidence and practice issues as they relate to adults are discussed. The evidence and application to practice related to children may differ significantly from information related to adults. When specific information about the care of children is available, it is summarized under its own heading.

Oral complications associated with cancer chemotherapy and radiation result from complex interactions among multiple factors. The most prominent contributors are direct lethal and sublethal damage to oral tissues, attenuation of immune and other protective systems, and interference with normal healing. Principal causes can be attributed to both direct stomatotoxicity and indirect stomatotoxicity. Direct toxicities are initiated via primary injury to oral tissues. Indirect toxicities are caused by nonoral toxicities that secondarily affect the oral cavity, including the following:

Understanding of mechanisms associated with oral complications continues to increase. Unfortunately, there are no universally effective agents or protocols to prevent toxicity. Elimination of preexisting dental/periapical, periodontal, and mucosal infections; institution of comprehensive oral hygiene protocols during therapy; and reduction of other factors that may compromise oral mucosal integrity (e.g., physical trauma to oral tissues) can reduce frequency and severity of oral complications in cancer patients (refer to the Oral and Dental Management Before Cancer Therapy and the Oral and Dental Management After Cancer Therapy sections of this summary for further information).[1]

Complications can be acute (developing during therapy) or chronic (developing months to years after therapy). In general, cancer chemotherapy causes acute toxicities that resolve following discontinuation of therapy and recovery of damaged tissues. In contrast, radiation protocols typically cause not only acute oral toxicities, but induce permanent tissue damage that result in lifelong risk for the patient.

Risk factors for oral complications (see Table 2) derive from both direct damage to oral tissues secondary to chemotherapy and indirect damage due to regional or systemic toxicity. For example, therapy-related toxicity to oral mucosa can be exacerbated by colonizing oral microflora when local and systemic immune function is concurrently compromised. Frequency and severity of oral complications are directly related to extent and type of systemic compromise.

Ulcerative oral mucositis occurs in approximately 40% of patients receiving chemotherapy. In approximately 50% of these patients, the lesions are severe and require medical intervention including modification of their cytotoxic cancer therapy. Normal oral mucosal epithelium is estimated to undergo complete replacement every 9 to 16 days. Intensive chemotherapy can cause ulcerative mucositis that initially emerges approximately 2 weeks after initiation of high-dose chemotherapy.[2-4]

Chemotherapy directly impairs replication of basal epithelial cells; other factors, including proinflammatory cytokines and metabolic products of bacteria, may also play a role. The labial mucosa, buccal mucosa, tongue, floor of mouth, and soft palate are more severely affected by chemotherapy than are the attached, heavily keratinized tissues such as the hard palate and gingiva; this may be caused by relative rate of epithelial cell turnover among high-risk versus low-risk oral mucosal tissues. Topical cryotherapy may ameliorate mucositis caused by agents such as 5-fluorouracil (5-FU) by reducing vascular delivery of these toxic agents to replicating oral epithelium.[5]

It is difficult to predict whether a patient will develop mucositis strictly on the basis of the classes of drugs that are administered. Several drugs are associated with a propensity to damage oral mucosa:

Anecdotal evidence suggests that patients who experience mucositis with a specific chemotherapy regimen during the first cycle will typically develop comparable mucositis during subsequent courses of that regimen.

Other oral complications typically include infections of the mucosa, dentition/periapices, and periodontium. Prevalence of these infections has been substantiated in multiple studies.[8-11] Specific criteria for determining risk of infectious flare during myelosuppression have not been developed. Guidelines for assessment primarily address both degree of severity of the chronic lesion and whether acute symptoms have recently (i.e., <90 days) developed. However, chronic asymptomatic periodontitis may also represent a focus for systemic infectious complications since bacteria, bacterial cell wall substances, and inflammatory cytokines may translocate into the circulation via ulcerated pocket epithelium.[10] In addition, poor oral hygiene and periodontitis seem to increase the prevalence of pulmonary infections in high-risk patients.[12]

Resolution of oral toxicity, including mucositis and infection, generally coincides with granulocyte recovery. This relationship may be temporally but not causally related. For example, oral mucosal healing in hematopoietic stem cell transplantation patients is only partially dependent on rate of engraftment, especially neutrophils.

Head and neck radiation can cause a wide spectrum of oral complications (refer to the list of Oral Complications of Radiation Therapy). Ulcerative oral mucositis is a virtually universal toxicity resulting from this treatment; there are clinically significant similarities as well as differences compared with oral mucositis caused by chemotherapy.[2] In addition, oral mucosal toxicity can be increased by use of head and neck radiation together with concurrent chemotherapy.

Head and neck radiation can also induce damage that results in permanent dysfunction of vasculature, connective tissue, salivary glands, muscle, and bone. Loss of bone vitality occurs:

These changes can lead to soft tissue necrosis and osteonecrosis that result in bone exposure, secondary infection, and severe pain.[11]

Oral Complications of Radiation Therapy

Unlike chemotherapy, however, radiation damage is anatomically site-specific; toxicity is localized to irradiated tissue volumes. Degree of damage depends on treatment regimen-related factors, including type of radiation utilized, total dose administered, and field size/fractionation. Radiation-induced damage also differs from chemotherapy-induced changes in that irradiated tissue tends to manifest permanent damage that places the patient at continual risk for oral sequelae. The oral tissues are thus more easily damaged by subsequent toxic drug or radiation exposure, and normal physiologic repair mechanisms are compromised as a result of permanent cellular damage.

Poor oral health has been associated with increased incidence and severity of oral complications in cancer patients, hence the adoption of an aggressive approach to stabilizing oral care before treatment.[1,2] Primary preventive measures such as appropriate nutritional intake, effective oral hygiene practices, and early detection of oral lesions are important pretreatment interventions.

There is no universally accepted precancer therapy dental protocol because of the lack of clinical trials evaluating the efficacy of a specific protocol. A systematic review of the literature revealed two articles on oral care protocols prior to cancer therapy.[3] One study examined the benefits of a minimal intervention precancer therapy (mostly chemotherapy) dental protocol, and the other examined the impact of an intensive preventive protocol on patients undergoing chemotherapy. Both studies had several flaws, including small sample size or the lack of comparison groups.[3]

The involvement of a dental team experienced with oral oncology may reduce the risk of oral complications via either direct examination of the patient or in consultation with the community-based dentist. The evaluation should occur as early as possible before treatment.[4,5] The examination allows the dentist to determine the status of the oral cavity before cancer treatment begins and to initiate necessary interventions that may reduce oral complications during and after that therapy. Ideally, this examination should be performed at least 1 month before the start of cancer treatment to permit adequate healing from any required invasive oral procedures. A program of oral hygiene should be initiated, with emphasis on maximizing patient compliance on a continuing basis.

Oral evaluation and management of patients scheduled to undergo myeloablative chemotherapy should occur as early as possible before initiation of therapy (refer to the list on Oral Disease Stabilization Before Chemotherapy and/or Hematopoietic Stem Cell Transplantation). To maximize outcomes, the oncology team should clearly advise the dentist as to the patients medical status and oncology treatment plan. In turn, the dental team should delineate and communicate a plan of care for oral disease management before, during, and after cancer therapy.[5]

Oral Disease Stabilization Before Chemotherapy and/or Hematopoietic Stem Cell Transplantation

The overall goal is to complete a comprehensive oral care plan that eliminates or stabilizes oral disease that could otherwise produce complications during or following chemotherapy. Achieving this goal will most likely reduce risk of oral toxicities with resultant reduced risk for systemic sequelae, reduced cost of patient care, and enhanced quality of life. If the patient is unable to receive the medically necessary oral care in the community, the oncology team should assume responsibility for oral management.

It is important to realize that dental treatment plans need to be realistic relative to type and extent of dental disease and how long it could be before resumption of routine dental care. For example, teeth with minor caries may not need restoration before cancer treatment begins, especially if more conservative disease stabilization strategies can be used (e.g., aggressive topical fluoride protocols, temporary restorations, or dental sealants).

Specific interventions are directed to:

Guidelines for dental extractions, endodontic management, and related interventions (see Table 3) can be used as appropriate.[6,7] Antibiotic prophylaxis prior to invasive oral procedures may be warranted in the context of central venous catheters; the current American Heart Association (AHA) protocol for infective endocarditis and oral procedures is frequently used for these patients.

Stages of assessment have been described relative to the hematopoietic stem cell transplant patient (see Table 4).[5] This model provides a useful classification for neutropenic cancer patients in general. Type, timing, and severity of oral complications represent the interaction of local and systemic factors that culminate in clinical expression of disease. Correlating oral status with systemic condition of the patient is thus critically important.

Selected conditioning regimens characterized by reduced intensity for myelosuppression have been used in patients. These regimens have generally been noted to significantly reduce the severity of oral complications early posttransplant, especially for mucositis and infection risk. The guidelines listed in Table 4 can be adjusted to reflect these varying degrees of risk, based on the specific conditioning regimen to be used.

Phase I: Before Chemotherapy

Oral complications are related to current systemic and oral health, oral manifestations of underlying disease, and oral complications of recent cancer or other medical therapy. During this period, oral trauma and clinically significant infections, including dental caries, periodontal disease, and pulpal infection, should be eliminated. Additionally, patients should be educated relative to the range and management of oral complications that may occur during subsequent phases. Baseline oral hygiene instructions should be provided. It is especially important to note whether patients have been treated with bisphosphonates (e.g., patients with multiple myeloma) and to plan their care accordingly.

Phase II: Neutropenic Phase

Oral complications arise primarily from direct and indirect stomatotoxicities associated with high-dose chemotherapy or chemoradiotherapy and their sequelae. Mucositis, xerostomia, and those lesions related to myelosuppression, thrombocytopenia, and anemia predominate. This phase is typically the period of high prevalence and severity of oral complications.

Oral mucositis usually begins 7 to 10 days after initiation of cytotoxic therapy and remains present for approximately 2 weeks after cessation of that therapy. Viral, fungal, and bacterial infections may arise, with incidence dependent on the use of prophylactic regimens, oral status prior to chemotherapy, and duration/severity of neutropenia. Frequency of infection declines upon resolution of mucositis and regeneration of neutrophils. This phenomenon appears to be more a temporal relation than a causative one, based on the predominant evidence. Despite the initial marrow recovery, however, the patient may remain at risk for infection, depending on status of overall immune reconstitution.

Salivary gland hypofunction/xerostomia secondary to anticholinergic drugs and taste dysfunction is initially detected in this phase; the toxicity typically resolves within 2 to 3 months.

In allogeneic transplant patients, while uncommon, hyperacute graft-versus-host disease (GVHD) can occur and can result in significant oral mucosal inflammation and breakdown that can complicate the oral course for patients. Clinical presentation will often not be sufficiently distinct to diagnosis this lesion. The clinical assessment is typically based on the patient experiencing more-severe-than-expected mucositis that will often not heal within the time line for mucosal recovery associated with oral mucositis caused by chemotherapy.

Phase III: Hematopoietic Recovery

Frequency and severity of acute oral complications typically begin to decrease approximately 3 to 4 weeks after cessation of chemotherapy. Healing of ulcerative oral mucositis in the setting of marrow regeneration contributes to this dynamic. Although immune reconstitution is developing, oral mucosal immune defenses may not be optimal. Generally stated, immune reconstitution will take between 6 and 9 months for autologous transplant patients and between 9 and 12 months for allogeneic transplant patients not developing chronic GVHD. Thus, the patient remains at risk for selected infection, including candidal and herpes simplex virus infections.

Mucosal bacterial infections during this phase occur less frequently unless engraftment is delayed or the patient has acute GVHD or is receiving GVHD therapy. Most centers will use systemic infection prophylaxis throughout this period (and, in many instances, longer) to reduce the risk of infections in general, a practice that positively influences the rate and severity of both systemic and local oral infections.

The hematopoietic stem cell transplant patient represents a unique cohort at this point. For example, risk for acute oral GVHD typically emerges during this time in allogeneic graft recipients.

Phase IV: Immune Reconstitution/Recovery from Systemic Toxicity

Oral lesions are principally related to chronic conditioning regimenassociated (chemotherapy with or without radiation therapy) toxicity and, in the allogeneic patient, GVHD. Late viral infections and xerostomia predominate. Mucosal bacterial infections are infrequent unless the patient remains neutropenic or has severe chronic GVHD.

Risk exists for graft failure, cancer relapse, and second malignancies. The hematopoietic stem cell transplant patient may develop oral manifestations of chronic GVHD during this period.

Phase V: Long-term Survival

Long-term survivors of cancer treated with high-dose chemotherapy alone or chemoradiotherapy will generally have few significant permanent oral complications.

Risk for radiation-induced chronic complications is related to the total dose and schedule of radiation therapy. Regimens that incorporate total body irradiation may result in permanent salivary gland hypofunction/xerostomia,[8] which is the most frequently reported late oral complication. Permanent salivary gland dysfunction can occur in autologous transplant patients in addition to nonautologous recipients. Other significant complications include craniofacial growth and developmental abnormalities in pediatric patients, and emergence of second malignancies of the head/neck region.

Routine systematic oral hygiene is important for reducing incidence and severity of oral sequelae of cancer therapy. The patient must be informed of the rationale for the oral hygiene program as well as the potential side effects of cancer chemotherapy and radiation therapy. Effective oral hygiene is important throughout cancer treatment, with emphasis on oral hygiene beginning before treatment starts.[1]

Management of patients undergoing either high-dose chemotherapy or upper-mantle radiation share selected common principles. These principles are based on baseline oral care (refer to the list of suggestions for Routine Oral Hygiene Care) and reduction of physical trauma to oral mucosa (refer to the list of Guidelines for Management of Dentures and Orthodontic Appliances in Patients Receiving High-Dose Cancer Therapy).

Routine Oral Hygiene Care

Guidelines for Management of Dentures and Orthodontic Appliances in Patients Receiving High-Dose Cancer Therapy [1]

Considerable variation exists across institutions relative to specific nonmedicated approaches to baseline oral care, given limited published evidence. Most nonmedicated oral care protocols use topical, frequent (every 46 hours) rinsing with 0.9% saline. Additional interventions include dental brushing with toothpaste, dental flossing, ice chips, and sodium bicarbonate rinses. Patient compliance with these agents can be maximized by comprehensive overseeing by the health care professional.

Patients using removable dental prostheses or orthodontic appliances have risk of mucosal injury or infection. This risk can be eliminated or substantially reduced prior to high-dose cancer therapy. (Refer to the list of Guidelines for Management of Dentures and Orthodontic Appliances in Patients Receiving High-Dose Cancer Therapy.)

Dental brushing and flossing represent simple, cost-effective approaches to bacterial dental plaque control. This strategy is designed to reduce risk of oral soft tissue infection during myeloablation. Oncology teams at some centers promote their use, while teams at other centers have patients discontinue brushing and flossing when peripheral blood components decrease below defined thresholds (e.g., platelets <30,000/mm3). There is no comprehensive evidence base regarding the optimal approach. Many centers adopt the strategy that the benefits of properly performed dental brushing and flossing in reducing risk of gingival infection outweigh the risks.

Periodontal infection (gingivitis and periodontitis) increases risk for oral bleeding; healthy tissues should not bleed. Discontinuing dental brushing and flossing can increase risk for gingival bleeding, oral infection, and bacteremia. Risk for gingival bleeding and infection, therefore, is reduced by eliminating gingival infection before therapy and promoting oral health daily by removing bacterial plaque with gentle debridement with a soft or ultra-soft toothbrush during therapy. Mechanical plaque control not only promotes gingival health, but it also may decrease risk of exacerbation of oral mucositis secondary to microbial colonization of damaged mucosal surfaces.

Dental brushing and flossing should be performed daily under the supervision of professional staff:

Patients skilled at flossing without traumatizing gingival tissues may continue flossing throughout chemotherapy administration. Flossing allows for interproximal removal of dental bacterial plaque and thus promotes gingival health. As with dental brushing, this intervention should be performed under the supervision of professional staff to ensure its safe administration.

The oral cavity should be cleaned after meals:

Preventing dryness of the lips to reduce risk for tissue injury is important. Mouth breathing and/or xerostomia secondary to anticholinergic medications used for nausea management can induce the condition. GVHD of the lips can also contribute to dry lips in allogeneic transplant patients. Lip care products containing petroleum-based oils and waxes can be useful. Lanolin-based creams and ointments may be more effective in moisturizing/lubricating the lips and thus protecting against trauma.

The terms oral mucositis and stomatitis are often used interchangeably at the clinical level, but they do not reflect identical processes.

Oral Mucositis:

Stomatitis:

Risk of oral mucositis has historically been characterized by treatment-based and patient-based variables.[4] The current model of oral mucositis involves a complex trajectory of molecular, cellular, and tissue-based changes. There is increasing evidence of genetic governance of this injury,[5-8] characterized in part by upregulation of nuclear factor kappa beta and inflammatory cytokines (e.g., tumor necrosis factor-alpha) and interleukin-1 in addition to epithelial basal cell injury. Comprehensive knowledge of the molecular-based causation of the lesion has contributed to targeted drug development for clinical use.[9] The pipeline of new drugs in development (e.g., recombinant human intestinal trefoil factor [10] may lead to strategic new advances in the ability of clinicians to customize the prevention and treatment of oral mucositis in the future.[11]

Erythematous mucositis typically appears 7 to 10 days after initiation of high-dose cancer therapy. Clinicians should be alert to the potential for increased toxicity with escalating dose or treatment duration in clinical trials that demonstrate gastrointestinal mucosal toxicity. High-dose chemotherapy, such as that used in the treatment of leukemia and hematopoietic stem cell transplant regimens, may produce severe mucositis. Mucositis is self-limited when uncomplicated by infection and typically heals within 2 to 4 weeks after cessation of cytotoxic chemotherapy.

Systematic assessment of the oral cavity following treatment permits early identification of lesions.[12-16] Oral hygiene and other supportive care measures are important to minimizing the severity of the lesion.

In an effort to standardize measurements of mucosal integrity, oral assessment scales have been developed to grade the level of stomatitis by characterizing alterations in lips, tongue, mucous membranes, gingiva, teeth, pharynx, quality of saliva, and voice.[12-14] Specific instruments of assessment have been developed to evaluate the observable and functional dimensions of mucositis. These evaluative tools vary in complexity.

Prophylactic measures and treatment options should be employed by practitioners for patients in the appropriate clinical settings. Specific recommendations for minimizing oral mucositis include the following:

Updated guidelines from the American Society of Clinical Oncology for the prevention and treatment of mucositis were published in 2007 [17] and include the following:

Specific recommendations against specific practices include the following:

Oral mucositis in hematopoietic stem cell transplantation patients produces clinically significant toxicities that require multiprofessional interventions.[18-25] The lesion can increase risk of systemic infection,[1] produce clinically significant pain,[26][Level of evidence: II] and promote oral hemorrhage. It can also compromise the upper airway such that endotracheal intubation is required. Use of total parenteral nutrition is often necessary because of the patients inability to receive enteral nutrition.

Once mucositis has developed, its severity and the patients hematologic status govern appropriate oral management. Meticulous oral hygiene and palliation of symptoms are essential. Some established guidelines for oral care include oral assessments twice daily for hospitalized patients and frequent oral care (minimum of every 4 hours and at bedtime) that increases in frequency as the severity of mucositis increases.

Oral care protocols generally include atraumatically cleansing the oral mucosa, maintaining lubrication of the lips and oral tissues, and relieving pain and inflammation. Several health professional organizations have produced evidence-based oral mucositis guidelines. These organizations include but are not limited to the following:

In many cases, there is similarity in recommendations across the organizations. The Cochrane Collaboration, however, uses a meta-analysis approach and thus provides a unique context for purposes of guideline construction.

Palifermin (Kepivance), also known as keratinocyte growth factor-1, has been approved to decrease the incidence and duration of severe oral mucositis in patients with hematologic cancers undergoing conditioning with high-dose chemotherapy, with or without radiation therapy, followed by hematopoietic stem cell rescue.[9][Level of evidence: I] The standard dosing regimen is three daily doses before conditioning and three additional daily doses starting on day 0 (day of transplant). Palifermin has also been shown in a randomized, placebo-controlled trial to reduce the incidence of oral mucositis in patients with metastatic colorectal cancer treated with fluorouracil-based chemotherapy.[30][Level of evidence: I] In addition, a single dose of palifermin prevented severe oral mucositis in patients who had sarcoma and were receiving doxorubicin-based chemotherapy.[31][Level of evidence: I]

In two randomized, placebo-controlled trials conducted in head/neck cancer patients undergoing postoperative chemoradiotherapy and in patients receiving definitive chemoradiotherapy for locally advanced head/neck cancer, intravenous palifermin administered weekly for 8 weeks decreased severe oral mucositis,[32,33][Level of evidence: I] as graded by providers using standard toxicity assessments and during multicycle chemotherapy.[31] Patient-reported outcomes related to mouth and throat soreness and to treatment breaks or compliance were not significantly different between arms in either trial. In one study, opioid analgesic use was also not significantly different between arms.[33]

Evidence from several studies has supported the potential efficacy of low-level laser therapy in addition to oral care to decrease the duration of chemotherapy-induced oral mucositis in children.[34][Level of evidence: I][35][Level of evidence: I]

Mucositis Management

Management of oral mucositis via topical approaches should address efficacy, patient acceptance, and appropriate dosing. A stepped approach is typically used, with progression from one level to the next as follows:

Normal saline solution is prepared by adding approximately 1 tsp of table salt to 32 oz of water. The solution can be administered at room or refrigerated temperatures, depending on patient preference. The patient should rinse and swish approximately 1 tbsp, followed by expectoration; this can be repeated as often as necessary to maintain oral comfort. Sodium bicarbonate (12 tbsp/qt) can be added, if viscous saliva is present. Saline solution can enhance oral lubrication directly as well as by stimulating salivary glands to increase salivary flow.

A soft toothbrush that is replaced regularly should be used to maintain oral hygiene.[17] Foam-swab brushes do not effectively clean teeth and should not be considered a routine substitute for a soft nylon-bristled toothbrush; additionally, the rough sponge surface may irritate and damage the mucosal surfaces opposite the tooth surfaces being brushed.

On the basis of nonoral mucosa wound-healing studies, the repeated use of hydrogen peroxide rinses for daily preventive oral hygiene is not recommended, especially if mucositis is present, because of the potential for damage to fibroblasts and keratinocytes, which can cause delayed wound healing.[36-39] Using 3% hydrogen peroxide diluted 1:1 with water or normal saline to remove hemorrhagic debris may be helpful; however, this approach should only be used for 1 or 2 days because more extended use may impair timely healing of mucosal lesions associated with bleeding.[40]

Focal topical application of anesthetic agents is preferred over widespread oral topical administration, unless the patient requires more extensive pain relief. Products such as the following may provide relief:

The use of compounded topical anesthetic rinses should be considered carefully relative to the cost of compounding these products versus their actual efficacy.

Irrigation should be performed before topical medication is applied because removal of debris and saliva allows for better coating of oral tissues and prevents material from accumulating. Frequent rinsing cleans and lubricates tissues, prevents crusting, and palliates painful gingiva and mucosa.

Systemic analgesics should be administered when topical anesthetic strategies are not sufficient for clinical relief. Opiates are typically used;[26][Level of evidence: II] the combination of chronic indwelling venous catheters and computerized drug administration pumps to provide PCA has significantly increased the effectiveness of controlling severe mucositis pain while lowering the dose and side effects of narcotic analgesics. Nonsteroidal anti-inflammatory drugs that affect platelet adhesion and damage gastric mucosa are contraindicated, especially if thrombocytopenia is present.

Although mucositis continues to be one of the dose-limiting toxicities of fluorouracil (5-FU), cryotherapy may be an option for preventing oral mucositis. Because 5-FU has a short half-life (520 minutes), patients are instructed to swish ice chips in their mouths for 30 minutes, beginning 5 minutes before 5-FU is administered.[41][Level of evidence: I] Oral cryotherapy has been studied in patients receiving high-dose melphalan conditioning regimens used with transplantation;[42,43] further research is needed.

Many agents and protocols have been promoted for management or prevention of mucositis.[44-46] Although not adequately supported by controlled clinical trials, allopurinol mouthwash and vitamin E have been cited as agents that decrease the severity of mucositis. Prostaglandin E2 was not effective as a prophylaxis of oral mucositis following bone marrow transplant, although studies indicate possible efficacy when prostaglandin E2 is administered via a different dosing protocol.

Check the list of NCI-supported cancer clinical trials for supportive and palliative care trials about mucositis that are now accepting participants. The list of trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI website.

Pain in cancer patients may arise from onset of the disease through survivorship and may be:[1]

Cancer pain causes increased morbidity, reduced performance status, increased anxiety and depression, and diminished quality of life (QOL). Dimensions of acute and chronic pain include the following:

Management of head and neck pain and oral pain may be particularly challenging because eating, speech, swallowing, and other motor functions of the head and neck and oropharynx are constant pain triggers.

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Oral Complications of Chemotherapy and Head/Neck Radiation ...

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