JIACD Continuing Education Oral Implications of Cancer Chemotherapy
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JIACD Continuing EducationJIACD Continuing Education Oral Implications of Cancer Chemotherapy Nicholas Toscano1 • Dan Holtzclaw 2 • Istvan A. Hargitai 3 Nicholas Shumaker4 • Heather Richardson 5 • Greg Naylor6 • Robert Marx 7 Abstract ancer ranks among the leading causes apy is of paramount importance. With optimal of death in the world today. Although coordination of efforts of the entire treatment Cchemotherapy has decreased mortal- team, including medical and dental provid- ity rates of patients with cancer, the morbidity ers, the patient’s survival and quality of life will associated with treatment continues. Initiation be enhanced. The purpose of this article is to and implementation of a review cancer chemother- comprehensive oral health apy, its associated compli- program that monitors and cations, and management treats patient before, dur- of the morbidity associ- ing, and after chemother- ated with this treatment. KEY WORDS: Cancer chemotherapy, oral complications, mucositis, xerostomia, osteonecrosis, management 1. Private practice, Washington DC, USA 2. Department of Periodontics, US Naval Hospital, Pensacola, Florida, USA 3. Department of Orofacial Pain and Oral Medicine, US Naval Hospital, Naples, Italy 4. Department of Periodontics, Naval Health Clinic, Quantico, Virginia, USA 5. Private Practice, Denver, Colorado, USA 6. Former Associate Professor, Naval Postgraduate Dental School, Bethesda, Maryland, USA 7. Professor and Chief of Oral & Maxillofacial Surgery, University of Miami Leonard M. Miller School of Medicine This article provides 2 hours of continuing education credit. Please click here for details and additional information. The Journal of Implant & Advanced Clinical Dentistry • 51 JIACD Continuing Education Internal factors include inherited mutations, hor- Learning Objectives mones, immune conditions, and mutations occur- 1,2 After reading this article, the reader should be ring from errors in metabolism. All of these able to: factors may act synergistically or in sequence to 1. Describe cancer treatment options and initiate the process of carcinogenesis. All can- the agents involved in chemotherapy. cer is caused by the malfunction of genes that 2. Discuss the dental complications asso- control cell growth, division, and maturation. ciated with cancer chemotherapy. In 2005, the American Cancer Society esti- 3. Identify and manage the dental complica- mated that 1,372,910 new cancer cases would be tions associated with cancer chemotherapy. diagnosed in the United States.1,3-10 This estimate did not include carcinoma in situ of any site except the urinary bladder, and also did not include basal INTrodUCTioN and squamous cell carcinomas on the skin. It Cancer ranks among the leading causes of was further estimated that approximately 570,280 death in the world today. As dentists we may Americans were expected to die of cancer in be called upon to manage patients undergo- 2005, which equates to more than 1500 people ing cancer therapy. While chemotherapy has per day. Overall, cancer is the second leading decreased mortality rates of patients with cancer, cause of death in the United States accounting the morbidity associated with the treatment can for 1 of every 4 deaths, and is exceeded only by impair quality of life and interrupt cancer treat- heart disease. For all cancer sites combined, Afri- ment. The goal of dental management for these can American men have a 25% and 43% higher patients is to prevent the development of oral cancer incidence and mortality rate than white complications. The oral health team needs to be men. For all cancer sites combined, African- involved with the patient’s treatment before, dur- American women have lower incidence rates than ing and after cancer therapy. The purpose of do white women, but have a 20% higher mortal- this article is to review cancer chemotherapy, ity rate. The five-year survival rate for all cancer the complications involved, and management sites has increased from 50% in 1974-1976, to of the morbidity associated with this treatment. 53% in 1983–1985, to 63% from 1992-1999.3-10 Cancer entails a variety of disease states characterized by the uncontrolled growth and CANcer TreaTMENT AND spread of abnormal cells. When this uncontrolled CHEMOTHERAPY growth is allowed to continue unchecked and Cancer is treated by surgery, chemotherapy, radi- untreated, death is likely to occur. The etiology ation therapy, hormones and immunotherapy.1-3 of cancer can be grouped into both external fac- Surgery is the most common method of treatment tors and internal factors. External factors include for primary tumors and may be curative in well tobacco, alcohol, chemicals, solar and ionizing circumscribed tumors. When a primary tumor radiation, infectious microorganisms, environmen- spreads and metastasizes, radiation therapy and tal pollutants, medications, and even nutrients. chemotherapy are necessary for definitive care. 52 • Vol. 1, No. 5 • July/August 2009 JIACD Continuing Education Rapidly dividing cancer cells are extremely radi- tionally, they induce cellular starvation as they osensitive making radiation therapy an effective mimic nutrients required for cell growth. Anti- adjunct or alternative for the regional treatment metabolites are cell-cycle specific and are of cancer. Chemotherapeutic regimens are used most effective during the S-phase of cell divi- effectively for disseminated cancer and may ulti- sion. Toxicities associated with these drugs mately provide relief of symptoms, prolong life, are seen in cells with elevated mitotic activ- and/or cure the disease. It is frequently used in ity. Examples of antimetabolites include purine conjunction with surgery and radiation therapy antagonists, pyrimidine antagonists, and folate to ensure treatment success, and may be used antagonists such as 6-mercaptopurine, 5-fluo- initially to decrease the size of the primary tumor rouracil, gemcitabine, and methotrexate.12,17,18 prior to surgery. Chemotherapy is responsible for the long term survival of patients with hema- Anti-tumor Antibiotics. These are a tologic and other malignancies.11-13 A major diverse group of compounds that are cell cycle advantage of chemotherapy is its ability to treat nonspecific. These agents bind with DNA, widespread or metastatic cancer, whereas sur- preventing RNA synthesis, disrupting protein gery and radiation therapies are limited to treat- formation, and ultimately causing cell death. ing cancers that are confined to specific areas. Anti-tumor antibiotics are not the same as anti- Chemotherapeutic regimens are intended to biotics used to treat bacterial infections. These destroy rapidly proliferating cancer cells. How- drugs cause uncoiling of DNA and prevent cell ever, these agents are nonspecific and normal reproduction. These agents are widely used host cells with high mitotic activity may also be in the treatment of a variety of cancers. Some adversely affected. Normal tissues that are sus- examples of antitumor antibiotics include: dox- ceptible to injury by chemotherapeutic agents orubicin, mitoxantrone, and bleomycin.12,17,18 include the oral and gastrointestinal mucosa, the hematopoietic system, and hair follicles.12,17,18 Steroid and Hormonal Agents. These agents include adrenocorticosteroids, estrogens, Alkylating Agents. The alkylating agents are antiestrogens, progesterones, and androgens. considered proliferation-dependent, but cell-cycle Hormonal agents alter the hormonally dependent phase nonspecific. DNA alkylation can occur intracellular environment of cancer cells. These anytime in the cell cycle. Examples of alkylating drugs may act as agonists to activate certain agents used in chemotherapy include: mechlore- receptors that ultimately inhibit tumor growth. thamine, cyclophosphamide, chlorambucil, ifosf- Alternately, they may act as antagonists that amide, procarbazine, cisplatin, and oxaliplatin.12,17,18 compete with natural hormones that promote tumor growth. Although the specific mechanism Antimetabolites. These drugs replace the of action is not entirely clear, steroid hormones natural building blocks in DNA molecules and modify the growth of certain hormone-depen- may alter the function of enzymes required for dent cancers. Tamoxifen, for example, is used cell metabolism and protein synthesis. Addi- for estrogen-dependent breast cancer.12,17,18 The Journal of Implant & Advanced Clinical Dentistry • 53 JIACD Continuing Education Plant Alkaloids. Plant derived alkaloids are of tumor, and therapy-related variables. Patient- anti-tumor agents that act specifically by blocking related variables include the overall health and cell division during mitosis. They are commonly immunity of the patient before and during che- used in the treatment of acute lymphoblastic leu- motherapy. Therapy-related variables involve kemia, Hodgkin’s and non-Hodgkin’s lymphomas, the regimen, frequency of treatment, dosage, neuroblastomas, Wilms’ tumor, and cancers of the and route of administration. Fortunately, many lung, breast and testes. Commonly used plant normal adult cells do not divide rapidly and are alkaloids include vincristine and vinblastine.12,17,18 less sensitive to the toxic effects of the chemo- therapy. Certain normal cells, however, such as Bisphosphonates. As a class, they are those of the oral and gastrointestinal mucosa, divided into two main categories: nitroge- hemopoietic system, and hair follicles divide nous bisphosphonates and non-nitrogenous more rapidly. Thus, the effects of chemother- bisphosphonates.