US Pharm. 2015;40(7)(Specialty&Oncology suppl):8-11.
ABSTRACT: Tongue cancer is a serious, life-threatening type of oral cancer. Oral cancer can develop in any part of the mouth, including the lips, gums, tongue, cheeks, and roof and floor of the mouth. Most cases of oral cancer are linked to tobacco use, heavy alcohol use, or infection with human papillomavirus (HPV). Sexually transmitted HPV infections (specifically, HPV-16) have been linked to a subset of oral cancers. Many oral cancers are detected by dentists through routine dental-hygiene procedures, and individuals should receive an oral examination at least annually. When identified early, tongue cancer is highly curable, but it can be deadly if it is not promptly diagnosed and treated.
Tongue cancer is a serious, life-threatening form of oral cancer. According to the American Cancer Society, oral cancer accounts for 2% to 4% of all cancers diagnosed annually in the United States. The risk of developing oral cancer is growing: Black persons have a 2-to-1 greater risk than white persons, men have twice the risk of women, and 75% of patients have used tobacco products and are also heavy users of alcohol.1-3 Oral cancer occurs most often in people aged >40 years, and men aged >50 years are at greatest risk. The incidence is increasing, especially among males. Approximately 37,000 people are diagnosed with oral cancer each year, and about 7,900 die from it. Fifty percent to 60% of patients survive >5 years after diagnosis. The 5-year survival rate for patients with localized disease at diagnosis is 83%, compared with 32% for those whose cancer has spread.1-3
Oral cancer can develop in any part of the mouth, including the lips, gums, tongue, cheeks, and roof and floor of the mouth.4,5 Cancer that forms in the front two-thirds of the tongue is classified as oral cancer; cancer that develops in the back third of the tongue is categorized as an oropharyngeal cancer (a type of head and neck cancer). Tongue cancer usually develops in the squamous cells lining the surface of the tongue. Mouth cancer occurs when cells on the lips or inside the mouth develop DNA mutations. These mutations allow cancer cells to grow and divide freely, whereas healthy cells die as they age. The accumulating mouth cancer cells can form a tumor.
Two lesions have been identified that may be precursors to oral cancer: leukoplakia (white lesion) and erythroplakia (red lesion). Although less common than leukoplakia, erythroplakia and lesions with erythroplakic components have a much greater potential for becoming cancerous.6 Any white or red lesion that does not heal or resolve on its own in about 2 weeks should be evaluated by a qualified physician and considered for biopsy to obtain a definitive diagnosis. An oral cancer often appears as a growth or sore in the mouth that does not heal. Tongue cancer is highly curable when it is detected early, but it can be life-threatening if not diagnosed and treated early. Over time, it may spread to other sites in the mouth, other areas of the head and neck, or other parts of the body.
There are three primary risk factors for oral cancer: tobacco use, alcohol use, and human papillomavirus (HPV).7-10 Less significant risk factors include increasing age and excessive sunlight exposure, with sun exposure affecting primarily the lips. Most cases of oral cancer are linked to heavy cigarette smoking, heavy alcohol use, or concurrent use of both substances. Use of both tobacco and alcohol multiplies a person’s risk much more than use of either substance alone. Pipe smokers are six times more likely than nonsmokers to develop oral cancers. People who use tobacco products such as dip, snuff, and chewing tobacco are about 50 times more likely to develop cancers of the cheek, gums, and lining of the lip. Because electronic smoking has been available for a relatively short period of time, its potential to cause oral cancers is unknown. Tobacco use in any form, including smoking just three cigarettes a day, increases the risk of HPV infection by about one-third.8
About 70% of oral cancers are caused by HPV infection.10 Infection with sexually transmitted HPV (specifically, HPV-16) has been linked to a subset of oral cancers. HPV-positive oropharyngeal cancers are associated with the increasing incidence of throat cancer in adults who do not smoke. Genital HPV, which is the most common sexually transmitted infection in the U.S., can be transmitted during oral sex (from mouth-to-genital or mouth-to-anus contact) or open-mouthed (“French”) kissing. The same types of HPV that infect the genital areas can infect the mouth and throat. HPV-positive oropharyngeal cancers typically develop in the throat, at the base of the tongue, and near or on the tonsils, making them difficult to detect. Although HPV-positive oropharyngeal cancer is often diagnosed at a later stage, people with HPV-positive cancer have a lower risk of dying or recurrence than those with HPV-negative cancer. It is likely that a complex interaction of many external and internal factors is involved in the development of HPV-positive cancers.
Signs and Symptoms
Tongue cancer is often mistaken for a cold sore that does not heal or a persistent sore in the mouth or lip area. Signs and symptoms of tongue cancer (TABLE 1) are similar to those of other oral cancers. Depending on the stage of development, the most common symptom of tongue cancer is a nonhealing sore in the oral cavity. Some symptoms of oral cancer or tongue cancer can also be attributed to a number of other medical conditions, so if symptoms persist beyond 2 weeks, it is important to seek medical advice, receive a thorough clinical examination, undergo laboratory testing, and obtain a definitive diagnosis.1,10-12
Treatment depends on the cancer’s location, stage, the patient’s overall health, and physician preference. The cancer stage (TABLE 2) helps direct standard treatment options. A lower stage (stage I-II) indicates a smaller cancer confined to one area. Stage IV indicates the presence of a larger tumor or that the cancer has spread to other areas of the head or neck or to other parts of the body. Treatment of oral cancer usually includes one or more of the following options: chemotherapy (ChT), radiation therapy (RT), and surgery. Some lesions may be treated with a combination of these therapies.12,13
ChT: ChT uses anticancer drugs to destroy cancer cells throughout the body. Its primary use is to retard the growth of a tumor and control undesirable symptoms if the cancer cannot be cured. ChT may be used for advanced tongue cancer that has spread to nearby lymph nodes. Drugs are administered by IV infusion into the arm or through a central line, usually once every 3 or 4 weeks, for two to three cycles or more. Different ChT drugs may be combined to attack cancer cells at varying stages of growth and to lessen the chance of drug resistance. ChT drugs commonly used for mouth and oropharyngeal cancers include docetaxel, cisplatin, and 5-fluorouracil (TPF).12-15 Common adverse effects (AEs) of TPF ChT include nausea, vomiting, hair loss, mucositis, electrolyte imbalances, hand-foot syndrome, nephrotoxicity, and ototoxicity.16-18
A randomized, open-label, phase III trial compared three cycles of TPF induction ChT (docetaxel 75 mg/m2, followed by IV cisplatin 100 mg/m2 and fluorouracil 1,000 mg/m2 per day, administered as continuous 24-hour infusion for 4 days) with three cycles of PF (IV cisplatin 100 mg/m2, followed by fluorouracil 1,000 mg/m2 per day as continuous 24-hour infusion for 5 days) in patients with stage III-IV squamous cell carcinoma.16,19 Overall survival was significantly better after treatment with TPF versus PF (hazard ratio 0.74, 95% CI, 0.58-0.94), with an estimated 5-year survival of 52% in TPF patients and 42% in PF patients. Median survival was 70.6 months (95% CI, 49.0-89.0) in the TPF group versus 34.8 months (22.6-48.0) in the PF group (P = .014).16,19
For tongue cancer, combining ChT with RT (chemoradiation) may be a better treatment strategy than using ChT alone. The primary reason for using ChT in combination with surgery or RT is to slow tumor growth and control symptoms if the cancer cannot be cured. This strategy can be used with RT as an alternative to surgery or used after surgery to reduce the risk of cancer recurrence.16
Targeted Therapy: Targeted drug therapy targets cancerous cells or tumors and is designed to interfere with cell growth at the molecular level. It is often combined with ChT and/or RT as part of a tongue cancer treatment plan. Cetuximab, a targeted therapy approved for treating head and neck cancer, is a recombinant human/mouse chimeric monoclonal antibody that binds specifically to the extracellular domain of the human epidermal growth factor receptor. Cetuximab stops the action of a protein that is found in various types of healthy cells but is more prevalent in certain types of cancer cells. When this protein is inhibited, proliferation is slowed considerably.11,12,15,20
Intensity-Modulated RT (IMRT): RT often uses high-energy x-rays, electron beams, or radioactive isotopes to destroy cancer cells. It can be delivered from a machine outside the body (external beam radiation) or from radioactive seeds and wires placed near the cancer (brachytherapy). RT may be the only treatment required if the cancer is detected early.12,16
IMRT uses a computer to calculate the precise radiation dosage needed to stop cancer cells from proliferating. High-dose RT is administered directly and with pinpoint accuracy to cancerous tissues of the tongue. The dosage is calculated to damage only the rapidly dividing cancer cells. IMRT causes only minimal damage to the normal tissues in the path of the radiation beam. Other advantages of IMRT include a more effective radiation dose, fewer AEs than with conventional RT, and a shorter procedure time. IMRT may be administered before or after surgery, and sometimes it is the only treatment necessary. RT involves 5 to 6 weeks of daily treatments.12,16
Surgery: Tongue cancer surgery involves removal of smaller primary tumors sufficient to achieve local cancer-free margins. For small tumors, this may be the only treatment needed. If the tumor is large, it may have spread to lymph nodes in the neck. In this case, a biopsy and/or dissection of the affected lymph nodes will likely be performed.6
Resection of the entire tumor from the tongue is done for smaller tumors, and the surgery usually causes only minor cosmetic or functional changes. Larger tumors can spread and cause swallowing and/or speech difficulties. Surgery for larger tumors may require removal of a portion of the tongue or jawbone, resulting in speech difficulties and/or facial disfiguration and possibly exacerbating other functional difficulties.6
Tongue-base surgery is required to remove larger tumors at the base of the tongue. These tumors are usually larger when first diagnosed, because they are more difficult to detect at an early stage, when they are smaller. The predominant early symptom is ear pain. Voice changes and difficulty swallowing may occur as the tumor grows. Because these tumors are diagnosed later in their development, the cancer may have already spread to the neck area. If lymph nodes are affected, they may need to be surgically removed and/or biopsied.6
Routine Dental Hygiene
Early detection and treatment of oral cancer provides patients with the best chance of a cure and may be life-saving. A routine oral examination (at least yearly) by a dentist is essential not only for proper dental hygiene, but also for detection of oral cancer at an early stage.21 Most dentists typically include an oral cancer examination as part of a dental-hygiene visit. These examinations are painless and take only a few minutes.
Impact of Nutrition on Quality of Life
An appropriate diet is important for both quality of life and survival of patients with oral cancer. In these patients, food intake can be impeded by functional restrictions in chewing and swallowing. In a study of 1,652 patients from 38 hospitals, chewing and swallowing were correlated with mobility of the tongue, mandible, and opening of the mouth.22 Thirty-five percent of patients lost weight, 41% maintained their weight, and 24% gained weight. Quality of life was significantly better in patients who maintained their weight and in those who gained weight compared with patients who lost weight. A normal diet was important for maintaining weight; mashed food, liquid food, and loss of appetite were closely associated with weight loss.
In the study, eating difficulties caused patients’ strength to deteriorate, thus restricting activity.22 RT had a negative impact on diet and weight by influencing sense of taste, causing dryness of the mouth, and resulting in swelling and discomfort when food was ingested. Pain and surgical scars in the region also made it uncomfortable for patients to eat hard, spicy, or sour foods. Support from a nutritional counselor in implementing a calorie-rich diet remedied these problems.22 Nutritional counseling and dietary support must be integrated into patient management to help patients maintain strength and keep from losing weight during the recovery period.
Increasingly more U.S. pharmacists and pharmacies are discontinuing the practice of selling tobacco products. Although this action is not being endorsed nationwide, any health-related publicity on the harmful effects of tobacco use should cause pharmacists to act on behalf of patients’ well-being. In this regard, pharmacists have an excellent opportunity to provide educational seminars for local physicians, nurses, pharmacy staff, and patients to promote concern for their patients’ good health. Topics that could be discussed include reminding patients and professionals of the harmful respiratory effects of long-term use of tobacco, the potential for tobacco products to cause various cancers that can reduce overall quality of life, and the reduction of tobacco-induced medical expenses.
Pharmacists have an important role when working with patients undergoing oral oncology regimens. Typically, patients taking oral agents have less physician-patient contact and oversight compared with patients receiving IV regimens. The pharmacist can clarify information about the disease state, explain medication administration, and assist in AE management. The pharmacist can maximize the effectiveness of the oral treatment by educating patients on how and when to take the medication and whether to take it with or without food. Counseling patients on possible drug interactions is vital for achieving optimal treatment effectiveness. Some of the common challenges patients face while on these regimens include lack of understanding of the disease or the medication, possible AEs, and fear and anxiety about affording the medication. All of these challenges can influence the patient’s adherence.
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20. Erbitux (cetuximab) product information. Branchburg, NJ: ImClone; April 2015.
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