Oral mucositis is a major toxic effect related to 5-fluorouracil (5-FU) therapy. Clinical studies have attempted to identify an effective antidote for this untoward side effect. Early pilot studies suggested that an allopurinol mouthwash could lessen 5-FU-induced mucositis. However, a randomized, double-blinded, placebo-controlled crossover study did not suggest that an allopurinol mouthwash had any prophylactic value in this clinical situation. An ongoing, randomized clinical protocol is testing cryotherapy as a method of inhibiting 5-FU-induced stomatitis. No clinically appropriate prophylactic measure for preventing 5-FU-induced mucositis has been found to date.
This review evaluates the state of the science and art of nursing management of acute oral complications of cancer. Published general oral hygiene protocols are reviewed briefly, and modifications to routine nursing care for hemorrhage, infection, pain, and problems associated with radiation to the head and neck are explored. There is a scarcity of research on which to base recommendations. The literature is primarily anecdotal or based on reports of experience at a single institution. Inconsistencies among such reports are numerous and have a detrimental effect on nursing management, as various clinicians provide different patient care instruction. Known principles, e.g., the need for adequate plaque removal and infection control, form the basis for nursing guidelines. Research is needed to guide clinical decision making, especially in defining the use of toothbrush substitutes. Problems in pain management appear to arise from inadequate application of known pain management principles. Since many of the oral complications are interrelated, nursing management must also take an integrated approach, and nursing care research must be conducted in the context of multidisciplinary care. Careful transfer of current research-based knowledge to practice and future research will help to achieve high-quality nursing management of acute oral complications.
New fever in a neutropenic patient mandates prompt institution of empirical broad-spectrum antibiotics. Traditional empirical regimens have relied on combinations that include an aminoglycoside. However, certain classes of newer antibiotics (e.g., third-generation cephalosporins, carbapenems, quinolones) include agents with a broad spectrum and high bactericidal activity that may provide therapeutic alternatives to combination regimens. We previously compared empirical monotherapy with ceftazidime to a combination regimen of cephalothin, gentamicin, and carbenicillin and found the regimens comparable with respect to percentage with success (survival without change of initial regimen; 62% vs 67%), success with modification (survival with additional antibiotics; 33% vs 29%) and failure (death; 5% vs 4%). Imipenem has a broader in vitro spectrum of activity than ceftazidime, particularly against gram-positive organisms and anaerobes, raising the possibility of equivalent or even improved efficacy as monotherapy. Accordingly, we are prospectively randomizing febrile, neutropenic patients to either empirical ceftazidime or imipenem therapy. Imipenem appears to be comparable to ceftazidime in this ongoing study but has not resulted in fewer modifications or secondary infections. Studies assessing the role of quinolones in the management of neutropenic patients are under way.
Certain disease entities or their management impose conditions that heighten risks of oral complications or systemic complications of oral origin. The pretreatment oral examination attempts to identify the main factors that will cause risk so that steps may be taken to control or eliminate as many as practical before treatment is begun. Additional tests may be indicated to provide more detailed information on which to base clinical diagnoses and oral therapy.
Taste and olfaction provide sensory information and sensory pleasure. Cancer therapies affect both. Chemotherapy has not been shown to produce dramatic losses of taste or smell, but systematic studies on various chemotherapeutic agents and types of cancer are lacking. Radiation therapy does produce clear losses of both taste and smell. Both chemotherapy and radiation therapy alter the pleasure produced by taste and smell through the formation of conditioned aversions. That is, foods consumed in proximity with the nausea of therapy come to be unpleasant. The impact of conditioned aversions can be diminished by providing a scapegoat food just before therapy. Alterations in foods may be beneficial to the cancer patient. Increasing the concentrations of flavor ingredients can compensate for sensory losses, and providing pureed foods that retain the cognitive integrity of a meal can benefit the patient who has chewing or swallowing problems.
Individuals undergoing cancer therapy may be at risk for a wide variety of oral problems that can significantly affect morbidity and mortality. Pretreatment oral assessment of these patients is an opportunity to identify and eliminate potential sources of sepsis and irritation. While preliminary studies strongly support the efficacy of pretreatment oral screening programs, a number of issues have yet to be addressed relative to patient-related and cost-related outcomes. Such studies should provide specific data regarding the focus of oral screening for specific malignancies, forms of cancer therapy, and oral pathology. As the aggressiveness of cancer therapy increases, comprehensive oral evaluation with clinical, radiographic, and adjunctive components before treatment is warranted.
Oral complications from cancer chemotherapy are well documented for the hematologic malignancies but are less well defined for cancers of the head and neck. This prospective study examined 82 patients with stage III or IV disease to determine the incidence and severity of oral sequelae following a total of 141 cycles of neoadjuvant chemotherapy. Taste alteration (37%) was the most frequent problem, followed by mucositis (30%) and ulceration (22%). Xerostomia, increased salivary flow, loss of appetite, weight loss, dysphagia, bleeding, and infection were also encountered. We conclude that oral problems are common following chemotherapy for head and neck tumors and that more aggressive investigational protocols will result in a much higher incidence and severity of problems. Prevention of these sequelae by conventional as well as investigational means is important to keep them from becoming dose-limiting problems.
Xerostomia is a common complication of radiation therapy to the head and neck. In such cases, the symptom is often permanent and leads to difficulty in mastication, wearing dentures, deglutition, and speaking. Other side effects include candidiasis and caries. Therapy is for the most part symptomatic and empirical. However, the use of sialogogues shows promise. Effective salivary substitutes and sialogogues that have minimal side effects need to be developed.
The role of mucositis in infectious complications in the patient with cancer is poorly understood. Consequently, neither the presence nor the severity of mucositis is routinely considered in the selection of specific antibacterial agents for the initial empirical therapy of the febrile cancer patient. In a study of children receiving remission induction chemotherapy for acute nonlymphocytic leukemia, the number of febrile days correlated more closely with the degree of mucositis than with the number of days of neutropenia. Oral mucositis appears to predispose cancer patients to systemic infections with alpha-hemolytic streptococci, Capnocytophaga, and Candida species. Overall, studies of single-drug versus combination therapy for the initial empirical therapy of febrile, neutropenic cancer patients indicate that monotherapy approaches the efficacy of combination therapy, although combination therapy may be preferred for certain cohorts of cancer patients. A concern that is closely related to the issue of combination therapy versus monotherapy is the need for vancomycin in the initial empirical regimen. Vancomycin appears to be the consensus drug of choice for patients with known gram-positive bacterial infections pending antibiotic susceptibility testing; however, there is disagreement as to whether the increased activity of vancomycin against gram-positive bacteria outweighs its expense and potential toxicity for inclusion in the initial empirical regimen. There is an explicit need for continued support of basic and clinical research to address these concerns.
Infection is the most common cause of morbidity and death in patients receiving chemotherapy for treatment of acute leukemia. Studies performed during the past decade suggest that over 30% of these infections originate from oral sources, particularly periodontal pockets and pericoronal flaps. Studies of large numbers of patients receiving a variety of myelosuppressive chemotherapy protocols are necessary to determine the risk-benefit ratio of dental treatment prior to chemotherapy.
The initial effect of anticancer therapy, such as radiation and chemotherapy, is on the rapidly proliferating cells of the oral epithelium. As a consequence, the epithelium may show atrophy and ulceration. The sites of these alterations are related to the rate of epithelial proliferation. Regions of rapid proliferation, such as the oral lining mucosa, show a greater frequency of ulceration than masticatory mucosa or skin. Subsequent changes in the mucosa reflect damage to connective tissue, including fibroblasts and blood vessels. This results in hyalinization of collagen, hypovascularity, and ischemia. Indirect effects of anticancer therapy may include granulocytopenia and reduced salivary secretion, so that the protective mucin coating of the epithelium is compromised. These changes result in tissue with reduced barrier function and impaired ability to heal and to resist entry of pathogens, thus increasing the risk of systemic infections.
Fungal surveillance cultures have been studied as potential predictors of invasive or disseminated mycoses. Several studies have demonstrated that the presence of Candida tropicalis in mucosal surveillance cultures has a high predictive value for invasive fungal infection due to this pathogen in granulocytopenic patients. By comparison, surveillance cultures for Candida albicans have a poor positive predictive value for invasive fungal infection. The value of routine surveillance cultures of the nares for Aspergillus spp. has not been consistently confirmed. The use of surveillance cultures for less common fungal pathogens, such as Trichosporon beigelii, also remains unclear. Fungal surveillance cultures of the inanimate hospital environment have proven useful in identifying the source of conidia in well-defined clusters or outbreaks of nosocomial aspergillosis and other mycoses. As investigational tools, fungal surveillance cultures also may be useful for studying the effects of new antifungal agents on mucosal flora. Fungal surveillance cultures, especially for C. tropicalis and possibly Aspergillus spp. in high-risk populations, may be useful when a pathogen-directed approach to antifungal therapy is used. However, the time required, diagnostic limitations, and expense of routine mucosal fungal surveillance cultures must be balanced against the effect of this information on therapeutic decisions. Empirical antifungal therapy and early diagnostic approaches for high-risk patients may obviate the need for routine fungal surveillance cultures while decreasing the frequency of invasive mycoses.
Oral ulcerations are frequently observed in cancer patients receiving chemotherapy or radiation therapy. Herpes simplex virus is the most common viral pathogen association with lesions. Reactivation of latent virus is responsible for the vast majority of culture-positive infections. The natural history of this virus has been well studied in selected patient populations. These infections may cause local complications and, if untreated, may not heal for weeks. Reactivation of the virus may occur predictably in patients after bone marrow transplantation or acute leukemia. Recognition that herpes simplex virus is present in oral lesions is of importance because of the availability of safe, effective antiviral therapy. Prospective, randomized, double-blind clinical trials have demonstrated that acyclovir is the most effective agent to treat or prevent herpes simplex virus infections in immunocompromised patients.
Individuals undergoing head and neck radiation treatments and cytotoxic chemotherapy for cancer are at risk for a variety of deleterious oral side effects. This added potential for oral problems places the cancer patient in a special category for oral health care management. Pretreatment intervention regimens directed at the supporting tissues of the teeth can effectively remove dental calculus deposits and cementum-imbedded bacterial toxins and reverse the inflammatory state of the periodontium back to normal. A variety of patient-applied fluoride agents are extremely effective in preventing severe radiation-associated dental decay, which is likely to occur after salivary gland dysfunction. Deficiencies in current patient management protocols and areas of current research are noted. Two essentials for a successful patient management program are emphasized: early referral of the patient to a knowledgeable dental team to ensure pre-cancer treatment oral health care intervention and long-term maintenance, and a family-oriented education and motivation program to enhance patient understanding and compliance.
Osteoradionecrosis (ORN) is one of the most serious complications arising from head and neck radiation therapy. Current research has shown that ORN represents nonhealing, dead bone and is not a state of infection. ORN is the result of functional and structural bony changes that may not be expressed for months or years. ORN may occur spontaneously or in response to wounding. Predisposing factors include absorbed radiation dose, fractionation, delivery modality, and dental status. Timing of dental extractions and other factors have also been shown to affect incidence. ORN may be reduced through early intraoral evaluation, treatment, and adequate healing time prior to beginning RT. Hyperbaric oxygen (HBO) therapy has been beneficial in the prevention and treatment of ORN. It is of paramount importance for the medical community to recognize the factors that may reduce ORN incidence, endorse oral care protocols, and acknowledge the value of HBO therapy in the prevention and treatment of this disease.
Radiation therapy (RT) and chemotherapy have increased long-term survival with certain cancers. The use of dental investigation and treatment of chronic or delayed oral complications is developing. Altered dental root development, enamel opacities, hypocalcifications, periodontal problems, and a higher caries rate are seen in children treated with chemotherapy. The psychosocial implications of long-term survival on routine dental care are important. Prevention and treatment of long-term oral complications of radiation therapy are changing. Osteoradionecrosis remains complicated and devastating. Strategies that avoid post-RT extractions include caries prevention, oral hygiene measures, meticulous restorative dentistry, overdentures, and improved posts for endodontically treated teeth. Guidelines for post-RT extractions vary greatly. Pediatric patients who receive head and neck irradiation may have total arrest of tooth and jaw development within the portal. The dentist must be able to diagnose and treat the variety of alterations already identified and should engage in scholarly research to answer the questions that remain.
Salivary gland dysfunction is a common side effect of cancer therapies. Salivary secretions are reduced rapidly after starting head and neck radiotherapy. Salivary gland dysfunction has also been linked to bone marrow transplantation and to cytotoxic chemotherapy. Salivary gland stimulation during radiation has been suggested as a means of reducing radiation damage. Results of an ongoing study investigating the effects of pilocarpine on radiation-induced salivary gland dysfunction suggest that parotid function was preserved, but not submandibular/sublingual function. Also, patients receiving pilocarpine had less frequent oral complaints. Further research is necessary to develop means of preventing or alleviating the salivary side effects of cancer therapies.
Acute and chronic graft-versus-host disease (GVHD) are significant complications of allogeneic bone marrow transplantation that occur when immunologically active T-cell lymphocytes are transplanted into an immunosuppressed recipient who is genetically disparate from the marrow donor. Oral GVHD lesions closely resemble those seen with a number of autoimmune connective tissue disease, including lichen planus, systemic sclerosis, lupus erythematosus, and Sjögren's syndrome. Mucosal erythema, atrophy, and ulceration are noted clinically; lichen planus-like lesions are the most distinctive oral lesions. Salivary gland changes include changes in both flow rate and sialochemistry. Oral involvement ranges between 33% and 75% for patients with acute GVHD and upwards of 80% for those with chronic GVHD. Management of oral GVHD lesions depends on successful systemic therapy, although topical steroids can be of help in some instances.
These studies of late effects related to cancer treatment to the head and neck demonstrate that these patients may develop a variety of abnormalities, the majority of which occur after irradiation. Once a child is "cured" of a primary malignant disorder, visits to oncologists usually continue but decrease in frequency. Regular visits to the dentist continue and are usually at least a biannual event. Attention to the details of the patient's previous medical history is of paramount importance if the delayed effects discussed here are to be suspected and recognized. Early diagnosis of thyroid and GH deficiencies and institution of appropriate hormone treatment may improve these children's growth and development. Recognition of cataracts and dry-eye syndrome is important to prevent visual difficulties. Careful oral examination and attention to the patient's general overall neurological presentation is an important adjunct to diagnosis of learning difficulties and early recognition of second tumors of the head and neck.
Oral complications of cancer therapy often have systemic consequences. Pain and discomfort are common and can lower intake of fluid and nutrients, which in severe cases can lead to dehydration and malnutrition, requiring hospitalization. Oral infections are frequent accompaniments of cancer treatment. Herpes simplex virus is the most common symptomatic oral viral infection, and, in latently infected patients the virus is frequently reactivated after cytoreductive therapy. Viral (infectious) oral mucositis is often indistinguishable from noninfectious mucositis. Bacterial infections are less commonly observed today, perhaps because of the routine use of empiric broad-spectrum antibiotics; however, many episodes of septicemia in neutropenic patients apparently originate from oral microorganisms. Fungal infections are frequent and are usually due to Candida species. Spread to the esophagus or systemic dissemination can occur. Noninfectious oral mucositis can be used as a marker of toxic effects in other organs, especially hepatic veno-occlusive disease. In bone marrow transplant patients with mucositis, hepatic veno-occlusive disease is six times more frequent than in such patients without mucositis.
