Maintaining Oral Health During Cancer Treatment JoAnn R. Gurenlian

Transcription

JoAnn R. Gurenlian, RDH, Ph.D.
Maintaining Oral Health
During Cancer Treatment
Educational Objectives
Upon completion of this course, the participant will be able to:
1. Recognize that a diagnosis of cancer is different for each individual.
2. Identify chemotherapeutic options for patients undergoing cancer treatment.
3. Describe the oral health manifestations associated with a weakened immune system
from cancer therapy.
4. Identify oral health protocols that will reduce morbidity and mortality.
Abstract
The National Cancer Institute estimates that approximately 1.6 million new cancer cases are
expected to be diagnosed this year and one-third of those individuals will die from their disease.
Cancer accounts for nearly 1of every 4 deaths and is the second most common cause of death
in the U.S. Fortunately, 13 million Americans with a history of cancer were alive in 2010, with
some still undergoing treatment.
Individuals who receive a diagnosis of cancer face many challenges as they proceed through
the continuum of care. They require support of all health care providers from the time of
diagnosis, through treatment, and after treatment is completed. This course will review the oral
effects of cancer treatment and protocols for reducing morbidity and mortality due to oral
complications of cancer therapy.
Introduction
Cancer is a significant health issue in the U.S. and worldwide. It represents the second leading
cause of death following heart disease. It is estimated that a total of 1,660,290 new cancer
cases and 580,350 cancer deaths will occur in the U.S. in 2013.1 Tobacco use and obesity are
the two main cancer-causing factors with each factor accounting for one-third of cancer deaths.1
Figure 1a provides information concerning the estimated new cases and deaths of leading
cancers among men and women. While lung cancer may be the leading cause of death among
both men and women, prostate cancer exceeds lung cancer in men in terms of new cases,
while breast cancer predominates in women. There have been decreases over time in terms of
cancer deaths. From 2000 to 2009, cancer death rates for both sexes combined decreased by
1.5% per year. However, incidence rates have increased for certain cancers including HPVassociated oropharyngeal and anal cancers, as well as for liver, kidney and thyroid cancers.2
Surveillance Epidemiology and End Results (SEER) reports reveal that an estimated 41,380
individuals will be diagnosed with oral cavity and pharyngeal cancer in 2013. Further,
approximately 7,890 will die from this disease in this year.3 The overall five year survival rate
for this cancer is 62.2%3 Figure 1b illustrates the survival rates for various cancers. Most
notably, the graph for oral cancer demonstrates decreases in 5 year relative survival rates with
spread of the disease. Since many oral cavity and pharyngeal cancers are diagnosed at a later
stage, prognosis remains poor.
All individuals are at risk for cancer. Lifetime risk projections for all cancers are 1 in 2 for men
and women.3 The lifetime risk for being diagnosed with oral and pharyngeal cancer is 1 in 92
for men and women.3
Screening for cancer is an important aspect of prevention, early diagnosis, treatment, and
prognosis. Research has demonstrated that the US population has met the Healthy People
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2010 goal for colorectal screening; however, declines were noted in all other recommended
cancer screening.4 Cancer survivors tend to have higher screening rates than the general
population, an important consideration for those concerned about second cancer diagnoses.4
Screening for oral and pharyngeal cancer is limited. Less than 20 percent of Americans report
receiving an oral cancer examination.5,6 Studies have demonstrated gaps in oral cancer
knowledge and examination procedures among physicians, dentists, and dental hygienists7-10
illustrating the need for greater attention to cancer awareness in health care settings.
Further, studies have demonstrated that cancer centers have not been implementing oral care
protocols for their patients.11-12 Specifically, oral care consultations were not required prior to
initiating cancer treatment, there were limited to no oral care protocols in place for patients
undergoing radiation treatment with identified oral pathology, most cancer centers did not have
a dental department team, and less than half of the cancer patients received preventive oral
care instructions.11 Another study showed that only 62% of head and neck radiation treatment
patients, 52% of intensive chemotherapy patient, and 13% of non-intensive chemotherapy
patients received referrals for oral prophylaxis prior to initiating oncology treatment. Less than
50% of patient were counseled on abstaining from a high cariogenic diet during cancer therapy.
Less than half of the oncology patients were given antifungal or herpetic prophylaxis treatment
during their cancer care. Finally, only 57% followed the recommended protocol of taking
antibiotic premedication prior to oral care when a central venous catheter had been placed.12
Given the prevalence of cancer in the US, it is likely that patients seen in dental and dental
hygiene practice settings will be experiencing a cancer diagnosis and subsequent treatment
while seeking regular oral health care. Whether the patient is diagnosed with an oral cancer or
cancer of another site, oral health professionals must be cognizant of the impact of maintaining
oral health during cancer care and the need for collaborating with oncology teams so that
cancer patient oral health requirements are adequately addressed. Procedures can be
established for ensuring safe and effective oral health care during the continuum of cancer care.
This paper will describe methods and special considerations for preserving oral health during all
phases of cancer treatment.
Information Gathering
One of the first steps in working with individuals with cancer is to identify them. Some patients
are reluctant to share their cancer diagnosis, assuming their general health condition has
nothing to do with their oral health. Other patients take time off from regular oral health care to
focus on cancer treatment not realizing that this care may place them at risk for oral infection.
Posting a sign in the reception area asking patients to inform the oral health professional if they
have been diagnosed with cancer is one way of beginning the conversations about oral care
during cancer care.
Knowing which patients are undergoing cancer therapy allows the front office staff to make
scheduling changes to benefit this patient. For example, the patient may be offered the last
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appointment of the day for an initial evaluation after being diagnosed with cancer. This allows
the dentist and dental hygienist to: gather key information to plan appropriate treatment to
reduce the negative oral effects of cancer treatment; share the common goal of providing
education about oral manifestations of cancer radiotherapy and chemotherapy; provide the
patient ample time to ask questions without being self-conscious about the need to keep the
appointment on schedule; and, provide time to teach the patient an oral self-exam. Patients who
are provided this appointment will appreciate that the dental team has forged a partnership with
them to prevent and effectively manage adverse effects of cancer therapy. Another
consideration of offering this appointment time is that patients may become emotional
discussing their diagnosis and impending treatment. Giving that person a chance to leave the
operatory without encountering other patients in the reception area reduces embarrassment and
discomfort.
Another aspect of information gathering is identifying members of the oncology team.
Depending on the type of cancer diagnosis, individuals may be working with a medical
oncologist, radiation oncologist, nurse practitioner, registered dietician, family practitioner, social
worker, and clinical psychologist. Oncology team contact information is important for
coordinating care should oral infection or other oral adverse effects occur during and posttreatment.
The next step is to identify the cancer protocol planned. The regimens of treatment, including
radiotherapy, chemotherapy, immunotherapy, hormone therapy and biological therapy need to
be defined including schedule of treatment, drugs used, and effects. Table Ia13 highlights
examples of chemotherapy drug types while Table Ib14 provides examples of the general and
oral side effects of chemotherapeutic agents.
Knowing the schedule of treatment (i.e., 14 chemotherapy treatments, one every three weeks; 6
treatments of chemotherapy every three weeks followed by one week of radiotherapy, surgery,
then additional chemotherapy) will assist the dentist and dental hygienist in scheduling oral
health appointments in between cancer treatment at a time when their white blood cell counts
are sufficient to prevent infection, and when their red blood cell and platelet counts are
adequate to prevent hemorrhage.
Typically, individuals undergoing cancer treatment will have blood studies performed just prior to
the next chemotherapy treatment. The oral health professional can obtain the results of these
studies and use them to determine if it is safe to perform dental and dental hygiene treatment. If
oral surgery or other invasive procedures are being planned, blood studies should be performed
24 hours before the scheduled appointment. Treatment should be postponed under the
following circumstances.
•
Platelet count is <75,000/mm3.
•
Abnormal clotting factors are present.
4
•
Absolute neutrophil count in <1000/mm3 (or consider prophylactic antibiotics).15
Some individuals will have a central venous catheter (port) placed as part of their chemotherapy
protocol. Consult with the oncologist to determine whether antibiotic premedication is needed
before providing any other health care.
Phases of Cancer Therapy
Individuals receiving cancer treatment undergo three phases of care: pretreatment, cancer
therapy, and end of cancer or recovery phase. Oral health professional involvement during each
phase of care is relevant.
Pretreatment Phase
Once the patient has been diagnosed with cancer, they should be advised to schedule an oral
health care appointment prior to the initiation of cancer treatment. Restorative dental care and
dental hygiene treatment should be performed at this time to minimize risk of infection during
cancer therapy. Any diseased areas of the mouth should be managed, including extraction of
hopeless teeth. Invasive procedures should be performed at least 14 days before head and
neck radiation begins and 7 to 10 days before myelosuppressive chemotherapy.15 Potential
sources of trauma, such as ill-fitting dentures, orthodontic brackets and bands, and other
appliances should be carefully evaluated.
Another consideration is to assess medications being used during cancer treatment for their
potential to produce xerostomic side effects. Patients undergoing head and neck radiotherapy
will have significant xerostomia. In these cases, both prescription and over-the-counter products
may be indicated to maintain moisture in the mouth, assist the patient with eating, speaking and
swallowing functions, and to minimize the formation of caries.
Fluoride therapy is an essential component of prevention during radiation treatment and
chemotherapy. During this phase of cancer treatment, in-office fluoride varnish can be provided,
and at home fluoride therapy can be implemented. Patients should be educated about their
increased risk for caries and the need for diligence in daily fluoride use. Although some
protocols include the use of fabricated custom tray appliances for home use, patients may find
these appliances unappealing. Rather than support nonadherence, an alternative is to use a
prescription fluoride gel or paste. For example, the dental professional can recommend
Colgate® PreviDent® Gel and 5000 Booster Prescription Strength Toothpaste. The important
element is daily use of fluoride and regular monitoring of caries potential during and after cancer
treatment.
Known risk factors for cancer should be assessed during the pretreatment phase of care.
Individuals who are addicted to smoking and/or alcohol should begin cessation programs.
Patients should be encouraged to adapt lifestyle changes including healthy food choices and
regular exercise.
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Approximately one-third of individuals diagnosed with cancer will develop oral complications
from treatment; these oral infections may be fatal.16 Therefore, it is important to educate
patients about the risk of oral infection, how to recognize signs of oral infection during cancer
treatment, and the need to seek immediate treatment for oral health concerns. Figure 1c17 offers
a simple visual depiction of how to perform an oral self-examination. Patients should be
instructed to perform this self-exam daily during cancer therapy checking for dryness,
ulcerations, swelling, bleeding, and any red, white or dark patches. The should be advised to
contact the dental or dental hygiene office immediately if they notice any of these findings so
they can be managed without delay. A short appointment for a professional comprehensive oral
examination can be scheduled to verify signs of infection or other complications of treatment.
Cancer Therapy Phase
Cancer therapy may be used for a short period of time (i.e., several months) or an extended
period of time (i.e., severe years or more). Patients cannot be expected to stop all oral health
care because they are undergoing cancer treatment. It is important to maintain periodic dental
and dental hygiene appointments to manage periodontal health, assess for signs of oral
complications of cancer care, and provide supportive therapy as needed. Table Ib demonstrates
that oral effects of cancer therapy may include mucositis, herpes infections, fungal infections,
radiation caries, and xerostomia. These conditions may occur separately or in combination, and
all require the attention of the oral health professional.
Mucositis is a side effect of both radiation and chemotherapy. It is an inflammatory condition
characterized by erythema, pain, and ulceration. The Mucositis Study Section of the
Multinational Association of Supportive Care in Cancer and the International Society for Oral
Oncology (MASCC/ISOO) refer to the term alimentary mucositis (AM) to describe mucosal
injury to the alimentary tract from the mouth to the anus. AM denotes that similarities in
conditions occur throughout the entire gastrointestinal tract.18
Mucositis increases the risk for systemic infections and increased pain. It can lead to
malnutrition and affect the patient’s quality of life.19 Guidelines for managing mucositis
presented by the MASCC/ISOO include the following.
•
Regular assessment of oral pain using validated, self-report pain instruments.
•
Topical anesthetics or other agents for oral comfort.
•
Initial and ongoing assessment of the oral cavity using validated instruments that include
both patient self-report and professional examination.
•
Use of preventive and therapeutic oral care regimen.
•
Regular, systematic, oral hygiene with brushing, flossing, bland rinses and moisturizers
should be implemented for all patients.18
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A variety of prescription and over-the-counter remedies have been used to treat mucositis with
mixed and limited results. Table Ic18 summarizes the MASCC/ISOO mucositis recommendations
guiding practitioners for helpful procedures as well as resources that are not supported by the
biomedical literature. More recently, a systematic review of interventions for preventing oral
mucositis was published through The Cochrane Collaboration. This review included an update
using 131 studies, examining 43 different interventions with a total of 10,514 patients. Evidence
found a benefit for the use of cryotherapy (ice chips) and keratinocyte growth factors (for
epithelialization of mucosal tissues) for the prevention of mucositis. The report indicated that
there was weak and unreliable evidence for the use of aloe vera, amifostine, glutamine
(intravenous), GM-SCF, honey, laser therapy, polymixin/tobramycin/amphotericin (PTA)
lozenges and paste, and sucralfate. There was no evidence supporting any benefit for using
chlorhexidine for the treatment of mucositis.20
Immunosuppression during cancer treatment may result in a herpes viral infections including
herpes simplex virus (HSV), varicella-zoster virus (HZV) resulting in shingles, Epstein-Barr
virus (EBV), and cytomegalovirus(CMV). The prevalence of oral viral infections during cancer
therapy has been close to 50% among neutropenic cancer patients21 and among patients with
ulcerative mucositis while undergoing head and neck treatment.22 Oral herpetic lesions can
present as recurrent herpes labialis or severe stomatitis throughout the mouth. Early diagnosis
and prompt management or viral infections is essential as systemic dissemination may occur
and can be fatal. Prophylactic regimens of acyclovir and valacyclovir is effective in reducing
HSV lesions in those cancer patients who are myelosuppressed. These medications, along with
famciclovir, are used to treat VZV, and ganciclovir is used to treat acute CMV infection.21,23-28
During the course of chemotherapy, patients may be administered corticosteroid medications to
reduce nausea and vomiting as well as antibiotics. These drugs change the balance of the
normal flora in the oral cavity and may result in bacterial and/or fungal infections. Candidiasis is
a common fungal infection that can occur. Lalla, et al reported that the prevalence of fungal
infections during chemotherapy was 38 percent.29 Oral fungal infections can be managed with
both topical agents such as a nystatin rinse or clotrimazole troches. However, if candidiasis
persists, systemic antifungal medication is recommended. In some cases, other fungal
organisms besides candidiasis my proliferate including Apergillus, Mucormycosis, and
Rhizopus. Microbiologic analysis is needed to distinguish these species from candidiasis.
Systemic therapy for these types of fungal diseases is critical in these cases as there is a high
risk of morbidity and mortality.29,30
Despite best intentions, it is not uncommon for oncology team members and dental
professionals to advise patients to cease tooth brushing and flossing regimens when platelet
counts fall below 40,000/mm3 and to substitute foam brushes for their regular tooth brush.31
However, patients can safely perform routine oral hygiene measures and should do so to reduce
oral biofilm accumulation, prevent caries, and control periodontal disease. Foam brushes cannot
adequately remove biofilm along the gingival margins, placing the patient at risk for gingival
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infection and bleeding. Should a patient present with significant bleeding during an oral
prophylaxis and debridement appointment, options to manage the bleeding include the use of
vasoconstrictors, clot-forming agents and tissue protectants, to reduce blood flow rates,
organize and stabilize clots, and help seal bleeding sites.31
Post-Treatment Phase
Reaching the end of cancer treatment and starting the recovery period is a momentous
occasion for the cancer patient. However, achieving this phase does not mean that there is no
longer a need for regular oral health evaluations. Patients may experience post-treatment
effects over time including salivary gland dysfunction and xerostomia, rampant caries, trismus,
soft tissue necrosis, osteoradionecrosis, and osteonecrosis of the jaw associated with
bisphosphonate use. Patients will need to be monitored frequently through regularly scheduled
follow-up appointments to assess potential problems or risk factors that need to be addressed.
For those patients who have been treated for oral cancer, there is a high risk of having a second
primary tumor. It is estimated that these individuals will have up to a 20 time higher risk of
developing a second cancer;32 therefore, continued and regular assessments are an important
aspect of the oral health protocol for individuals with cancer.
Salivary gland dysfunction leading to xerostomia is a long-term complication of head and neck
radiotherapy. Xerostomia also occurs with chemotherapy treatment; however, the condition is
usually reversible. With xerostomia, dry soft tissues may become fragile, ulcerate, and cause
mucositis. Xerostomia associated with radiation therapy poses a risk for rampant cervical caries.
In addition, patients are at risk of developing fungal infections and difficulty speaking,
swallowing or eating due to dry mouth. The key to managing xerostomia is to maintain a moist
mouth. Over-the-counter sprays, rinses, gels, and toothpastes are readily available for
managing mild cases of dry mouth. Prescription medications such as pilocarpine or cevimeline
are recommended for severe cases of xerostomia. To reduce the risk of radiation caries, daily
use of a high-potency fluoride gel is recommended.33 In addition, patients should be advised to
avoid candy, gum, and soda unless they are sugar-free, and avoid spicy or acidic foods,
tobacco products and alcohol.
Altered taste is another side effect of chemotherapy that is aggravated by mucositis affecting the
tongue. Some individuals will complain of a metallic taste in their mouth or report that foods that
look and smell appealing, but simply do not taste good. In these cases, it is important to
reassure the patient that their taste sensation will return within several weeks post
chemotherapy. The patient should be encouraged to maintain adequate nutrition during this
time until the altered taste resolves. Patients undergoing radiotherapy may complain of taste
loss as well. This condition is due to damage to the taste receptors. In this situation, it may take
6 to 8 weeks or longer for taste receptors to become functional again. Zinc sulfate supplements
may be useful in recovering sense of taste.34,35
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Trismus is a long-term complication of radiation treatment. It is the inability to open the mouth
properly as a result of fibrotic changes to the muscles of mastication and temporomandibular
joint. Trismus typically manifest itself three to six months post radiotherapy. Physical therapy,
including stretching exercises during and post treatment, are needed to manage this condition.
A daily home exercise program may be recommended as well.
Patients exposed to head and neck radiation treatment have a lifelong risk of developing
osteoradionecrosis (ORN). This condition affects the mandible more frequently than the maxilla,
and is characterized by pain, loss of sensation, fistula, infection and pathologic bone fracture.
Treatment for ORN includes topical antibiotics, antiseptics, analgesics, local resection of bone
sequestra, and hyperbaric oxygen therapy. In severe cases, a partial mandibulectomy may be
needed. However, prevention during the pretreatment phase of cancer care is the best course of
action. The dentist should carefully evaluate the dentition, periodontium, and mucosa for
disease that could lead to serious infection. Evidence of oral disease should be eliminated
during pretreatment including restorative care and extractions using primary intention healing.36
Additionally, some cancer patients will be treated with intravenous bisphosphonates placing
them at greater risk for bisphosphonate-related osteonecrosis of the jaw (BRONJ). Preventive
dental intervention (such as a comprehensive oral examination, extraction of hopeless teeth,
achieving optimal periodontal health, and performing invasive dental procedures prior to the
start of therapy) will help reduce, but not completely eliminate, the risk of BRONJ. Placement of
dental implants is not recommended in the oncology patient exposed to a frequent dosing
schedule of bisphosphonate medications such as zoledronic acid and pamidronate.37 The
American Association of Oral and Maxillofacial Surgeons Task Force on Bisphosphonate-related
Osteonecrosis of the Jaws has developed a staging system for BRONJ accompanied by
treatment strategies. This information is presented in Table 1d.37
Teaching Patients How to Maintain Oral Health
Patients undergoing cancer therapy need to be reminded to maintain meticulous oral health
during and after their treatment. In addition to performing a daily self-exam to identify potential
for infection or adverse oral effects of cancer treatment, patients need to appreciate the
importance of adhering to an oral home care regimen to minimize biofilm accumulation.
Maximizing an oral health home regimen should include gentle cleansing using tooth brushes
with soft or ultrasoft bristles, a toothpaste with fluoride and both antibacterial and antiinflammatory properties (Colgate Total®), use of floss or other interdental aides, and an
antiseptic mouth rinse. A common myth is to recommend avoiding the use of alcohol-containing
mouth rinses (ACM) due to the risk of alcohol causing oral cancer as well as dryness of the
mouth. However, these claims are unsupported.38-42 Use of ACM may be beneficial in reducing
biofilm throughout the mouth as well as managing oral dryness.
Patients should be advised that they will require periodic follow-up appointments on a regular
basis to monitor their progress with cancer treatment and to have examinations for the presence
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of second primary tumors or cancer recurrence. All aspects of the head and neck examination
should be well documented at each dental and dental hygiene appointment. Pacak provided a
sample form for documentation of findings of the oral examination that is both comprehensive
and easy to use.43
In some cases, dental professionals are reluctant to perform oral health care procedures while
the patient is undergoing cancer therapy. There is no reason to forego dental and dental
hygiene appointments during this time. Rather, it is critical to continue to provide preventive and
supportive care and to assist the patient in maintaining oral health. Patients should be assured
that continued oral health care is part of promoting general health during the fight against
cancer. Key information for ensuring oral health is summarized in the brochure “Maintaining Oral
Health During Cancer Treatment”, which is available at www.richmondinstitute.com.
Conclusion
With almost 45 percent of the US population expected to receive a diagnosis of cancer in their
lifetime, it is highly likely that oral health care providers will be treating these individuals during
the course of cancer care. Dentists and dental hygienists have a unique opportunity to assist
these individuals throughout the continuum of care ensuring that adverse oral effects are
minimized. Helping patients achieve and maintain oral health during cancer treatment may
improve their changes for a successful outcome. Remaining current on cancer protocols and
advocating for partnership with the oncology team demonstrates a commitment to reducing
morbidity and mortality from oral disease.
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39. Gandini S, Negri E, Boffetta P, et al. Mouthwash and oral cancer risk quantitative meta-analysis of
epidemiologic studies. Ann Agric Environ Med 2012;19:173-180.
40. Fischman SL, Aguirre A, Charles CH. Use of essential oil-containing mouthrinses by xerostomic
individuals: determination of potential for oral mucosal irritation. Am J Dent 2004;17:23-26.
41. Kerr AR, Katz RW, Ship JA. A comparison of the effects of 2 commercially available nonprescription
mouthrinses on salivary flow rates and xerostomia. Quintessence Int 2007;38:e440-e447.
42. Spolarich AE, Gurenlian JAR. Dispel the myths. Dimensions of Dent Hyg 2013;11(4):20-24.
43. Pacak DK. Developing a documentation protocol. Dimensions of Dent Hyg 2011;April;38-43.
13
List of Figures and Tables
Table 1 a. Chemotherapy Drug Types
Table 1 b. Examples of Chemotherapeutic Agents and Side Effects
Table 1 c. MASCC/ISOO Mucositis Recommendations
Table 1 d. BRONJ Staging and Treatment Strategies
Figure 1 a. Leading New Cancer Cases and Deaths – 2013 Estimates
Figure 1 b. Survival Rates based on Stage at Diagnosis
Figure 1 c. Oral Cancer Pictorial Self-Exam
Author Bio
JoAnn R. Gurenlian, RDH, PhD, is Professor and Graduate Program Director of the Department
of Dental Hygiene at Idaho State University. She is the President of the International Federation
of Dental Hygienists and Past President of the American Dental Hygienists’ Association. Dr.
Gurenlian maintains a column entitled “Looking Ahead” in RDH magazine, and is the co-author
of a textbook “Preventing Medical Emergencies: Use of the Medical History.” She has published
over 160 papers, and has been active in dental hygiene as a leader, educator, clinical,
administrator, researcher, and international speaker.
Author Contact Information
JoAnn R. Gurenlian, RDH, PhD
45 Linden Avenue
Haddonfield, NJ 08033
[email protected]
Disclosures
The author has served as a key opinion leader as well as a member of the COHA Board and
Global Toothbrush Advisory Board for Colgate.
14
Table Ia: Chemotherapy Drug Types
Drug
Action
Examples
Differentiating agents
Acts on cancer cells to make them
mature into normal cells
Retinoids (Atralin®)
Bexarotene (Targretin®)
Arsenic trioxide (Arsenox®)
Hormone therapy
Alter the action or production of
female or male hormones
Prevents the cancer cell from using
the hormone it needs to grow
Prevents the body from making the
hormones
Anti-estrogens (tamoxifen)
Aromatase inhibitors (Arimidex®)
Progestins (Megace®)
Estrogens
Anti-androgens (Casodex®)
Gonadotropin-releasing hormone (GnRH)
Immunotherapy
Stimulates natural immune systems
to more effectively recognize and
attack cancer cells
Monoclonal antibody therapy (Rituxan®)
Interleukin -2 (IL-2)
Lenalidomide (Revlimid®)
Alkylating agents
Directly damage DNA to prevent the
cancer cell from reproducing
Can cause long-term damage to
bone marrow
Increases risk of leukemia
Nitrogen mustards (mechlorethamine,
Cytoxan®)
Nitrosoureas (streptozocin)
Alkyl sulfonates (busulfan)
Triasines (dacarbazine)
Ethylenimines (thiotepa and altretamine)
Antimetabolites
Interferes with DNA and RNA
growth
Damages cells during the S phase
5-fluorouracil (5-FU) methotrexate
6-mercaptopurine (6-MP)
Pentostatin
Anti-tumor antibiotics
Interfere with enzymes involved in
DNA replication
Works in all phases of the cell cycle
Daunorubicin
Doxorubicin (Adriamycin®)
Epirubicin
Idarubicin
Bleomycin
Topoisomerase inhibitors
Interfere with enzymes called
topoisomerases which help
separate strands of DNA so they
can be copied
Topotecan
Irinotecan (CPT-11)
Etoposide (VP-16)
Teniposide
Mitotic inhibitors
Stops mitosis or inhibits enzymes
from making proteins needed for
cell reproduction
Works during the M phase of the
cell cycle; can damage cells in all
phases
Taxanes (Taxol®, Taxotere®)
Epothilones (Ixempra®)
Vinca alkaloids (vinblastine)
Estramustine (Emcyt®)
15
Drug
Action
Examples
Corticosteroids
Commonly used as anti-emetics
caused by chemotherapy
Prednisone
Methylprednisone (Solumedrol®)
Dexamethasone (Decadron®)
Source: American Cancer Society. Chemotherapy principles: an in-depth discussion. Available at: http://
www.cancer.org. Accessed July 10, 2013.
16
Table Ib: Examples of Chemotherapeutic Agents and Side Effects
Agent
General Side Effects
Oral Side Effects
Cyclophosphamide
(Cytoxan®)
Myelosuppression
Leukopenia
Increased risk of infection
Moderate to severe emesis
Anorexia
Abdominal discomfort/pain
Diarrhea
Hemorrhagic colitis
Jaundice
Alopecia
Skin or nail pigmentation
Hemorrhagic cystitis
Interstitial pulmonary fibrosis and pneumonitis
Acute cardiac toxicity
Congestive heart failure
Sterility
Asthenia, dizziness, depression or headache
Musculoskeletal pains and rheumatic syndromes
Oral mucosal ulceration
Temosolomide
(Temodar®)
Nausea, vomiting, constipation, diarrhea
Headache, fatigue, asthenia, fever, back pain
Convulsions, hemiparesis, dizziness, amnesia, insomnia
Peripheral cardiac edema
Viral infection
Adrenal hypercorticism
Urinary tract infection
Upper respiratory tract infection, pharyngitis
Diffuse erythematous skin rash
Anxiety, depression
Weight gain
Myalgia
Abnormal and double vision
Opportunistic infections
Leukemia, glioblastoma multiforme
Mouth or tongue sores
Carboplatin
Bone marrow suppression
Thrombocytopenia
Vomiting, abdominal pain
Peripheral neuropathies
Abnormal liver function tests
Ototoxicity
Dehydration
Mucositis
Stomatitis
17
Agent
Oral Side Effects
Cisplatin
Nephrotoxicity
Emesis, nausea, diarrhea
Sensory polyneuropathy
Ototoxicity, headache, strokes
Tinnitus, hearing loss
Myelosuppression
Anemia
Optic neuritis, cortical blindness, blurred vision
Myocardial infarction, CVA, cerebral arteritis
Anaphylactic-like reactions
Transient elevated liver enzymes
Soft tissue toxicity
Rash, alopecia, digital necrosis
No significant effects
reported
5-fluorouracil (5-FU)
Esophagopharyngitis, anorexia, nausea, vomiting,
diarrhea,
Leukopenia (principally granulocytopenia),
thrombocytopenia, anemia, Alopecia, dermatitis
(principally pruritic maculopapular rash
Stomatitis
Methotrexate
Myelosuppression
Anemia, aplastic anemia, thrombocytopenia
Nausea, vomiting, diarrhea
Anorexia, GI bleeding
Acute hepatitis, chronic fibrosis and cirrhosis
Opportunistic infections
Headache, dizziness, drowsiness, blurred vision,
moodiness, tinnitus
Pulmonary toxicity
Interstitial pneumonitis
Renal insufficiency
Malaise, fatigue, chills
TEN, Stevens-Johnson syndrome, erythema multiforme
Alopecia
Pericarditis, pericardial effusion, myocardial ischemia,
hypotension
Conjunctivitis
Speech impairment
Ulcerative stomatitis
Gingivitis
Pharyngitis
Doxorubicin
(Adriamycin®)
Heart failure, late cardiomyopathy, congestive heart
failure
Myelosuppresion resulting in suprainfection and/or
hemorrhage
Alopecia
Hyperpigmentation of nailbeds
Oncholysis
Nausea,vomiting, bleeding, local infection, colonic
ulceration
Renal insufficiency
Secondary leukemia
Stomatitis
Mucositis
Tongue
hyperpigmentation
18
Agent
Oral Side Effects
Mitoxantrone
Myelosuppression
Secondary leukemia
Left ventricular systolic function and congestive heart
failure
Blue streaking in or around the vein and of skin
Renal insufficiency
Drug rash with eosinophilia and systemic signs (DRESS)
Green urine
Amenorrhea
Mucositis
Stomatitis
Mouth pain
Irinotecan (CPT-11)
“Early” diarrhea, diaphoresis, stomach cramping
Late diarrhea can be life threatening
Ulcerative and ischemic coliltis
Nausea, vomiting
Leukopenia, anemia, neutropenia
Asthenia, fever, pain, headache, chills, minor infections,
edema abdominal enlargement
Minor upper respiratory infections
Weight loss
Dehydration
Alopecia, sweating, rash, parasthesias
Dyspnea, increased coughing, rhinitis
Insomnia, dizziness
Myocardial ischemia
Renal insufficiency
Muscular contractions and cramps
Increased salivation
Mucositis
Stomatitis
Paclitaxel (Taxol®)
Bone marrow suppression
Fever
Bleeding episodes
Sinus bradycardia, tachycardia, and premature beats
Neurotoxicity
Hepatic toxicity
Edema
Transient skin changes
Alopecia (usually irreversible)
Myalgia and/or arthralgia
Cellulitis
Mucositis
Stomatitis
Sores of the lips
Vinblastine (Velban®)
Leukopenia and septicemia
Leukemia
Alopecia
Nausea, vomiting, anorexia,
Pharyngitis, diarrhea, rectal bleeding
Myocardial infarction, CVA, Raynaud’s phenomenon
Shortness of breath, severe bronchospasm, progressive
dyspnea
Malaise, bone pain, weakness, dizziness, myalgia,
ototoxicity
Stomatitis
Metallic taste
Jaw pain
Vesiculation of the
mouth
19
Agent
Oral Side Effects
Estramustine (Emcyt®)
Gynecomastia, impotence, breast tenderness and
enlargement
Exacerbation of pre-existing heart disease
Nausea, diarrhea, GI upset
Dyspnea
Leukopenia
Lethargy, insomnia
Easy bruising, pruritis, dry skin
Hoarseness
Sore throat
Dexamethasone
(Decadron®)
Bradycardia, cardiac arrest, cardiac arrhythmias, cardiac
enlargement, congestive heart failure
Muscle weakness, steroid myopathy, osteoporosis,
compression fractures, aseptic necrosis of femoral and
humeral heads, pathologic bone fractures, tendon rupture
Peptic ulcer, bowel perforation, abdominal distention,
nausea, increased appetite, esophagitis
Cushingoid state
Convulsions, increased intracranial pressure, vertigo,
malaise, headache, psychic disturbances
Weight gain, hirsutism,
Cataracts, glaucoma, increased intraocular pressure,
exophthalmos
Impaired wound healing, petechiae, ecchymosis, dry
skin, thinning scalp hair, increased sweating, rash,
urticaria
Euphoria, insomnia, mood swings, personality changes,
severe depression, psychosis
Reversible hepatomegaly
Angioedema
Bortezomib (Velcade®)
Asthenia, pyrexia, headache, insomnia, dizziness,
dehydration
Nausea, diarrhea, constipation, decreased appetite,
vomiting, pain
Thrombocytopenia, neutropenia
Peripheral neuropathy, neuralgia, hemorrhagic stroke,
motor dysfunction
Arthralgia, pain in limb, back pain, bone pain
Hypotension (orthostatic)
Edema, hypertension, aggravated atrial fibrillation and
atrial flutter
Dyspnea, cough, upper and lower respiratory tract
infections
Rash, herpes zoster, pruritis
Dysgeusia, impaired hearing, bacteremia, herpes viral
infections,, septic shock
Blurred vision
Hepatitis
Anorexia, agitation, confusion, psychotic disorder, mental
status change, suicidal ideation
Abnormal taste
Stomatitis
Angioedema and
Laryngeal edema
Oral candiasis
20
Agent
Oral Side Effects
Imatinib (Gleevec®)
Nausea, vomiting, edema, tumor necrosis, muscle
cramps
Neutropenia, thrombocytopenia, anemia
Cardiac edema
Headache, CNS hemorrhage
Skin rash, pruritis, petechiae, alopecia
Nasopharyngitis, cough, upper respiratory tract infection
weight increase
renal failure
depression, anxiety, memory impairment
breast enlargement
periorbital edema, conjunctivitis, blurred vision
Mouth ulceration
Taste Disturbance
Angioedema
Tretinoin (ATRA or
Atralin®)
Peeling, dry skin, burning, stinging, erythema, pruritis
Stinging of the eye
Isolated vaginal bleeding
Xerostomia
Tamoxifen
Hot flashes, nausea, vomiting
Endometrial abnormalities – adenocarcinoma, uterine
sarcoma, hyperplasia, endometrial polyps
Endometriosis, vaginal bleeding, discharge, altered
menses
Bone pain, severe hypercalcemia
Jaundice, hepatitis
Ocular toxicity
CVA, edema, phlebitis, thromboembolism
Pulmonary embolism
Depression, delusional syndromes
Anorexia,
Hair loss
Visual memory, word fluency, processing speed tasks
problems
No significant effects or
complications reported
Leuprolide (Lupron®)
Hot flashes, gynecomastia, breast enlargement and
tenderness
Depression, emotional lability
Headache, dizziness, blurred vision
Vaginal dryness, urinary frequency, hematuria, testicular
and breast soreness/pain, testicular atrophy, erectile
dysfunction
Peripheral edema, hypertension, hypotension, murmur,
phlebitis, deep vein thrombosis, stroke, sudden cardiac
death, myocardial infarction
Constipation, anorexia, nausea, vomiting
Skin rash, hair loss, ecchymosis
Bone pain
Anemia, leukopenia, hemoptysis
Dyspnea, sinus congestion, cough, pulmonary fibrosis
Granulomas
Fibromyalgia, hearing disorder, hard nodule in throat,
weight gain, increased uric acid
Difficulty with/painful urination, bladder spasm
Hyperglycemia
Gingival hemorrhage
Gingivitis
Dry mucous membranes
Dysphagia
21
Agent
Oral Side Effects
Rituximab (Rituxan®)
Fever, chills, asthenia, headache, abdominal pain
Hepatitis
Myocardial infarction, ventricular fibrillation, cardiogenic
shock
Rhinitis, bronchospasm, pneumonitis
Nausea, vomiting
Leukopenia, thrombocytopenia, neutropenia
Myalgia, dizziness, pruritis, rash, urticarial
Renal insufficiency
Disease progression of Kaposi’s sarcoma
Bilateral conjunctivitis
Pyelonephritis
Throat irritation
Angioedema
Interleukin-2 (IL-2)
Hypotension
Generalized body edema
Ascites
Pulmonary edema
Chills, fever
Headache, malaise
Nausea, vomiting
Loss of appetite, diarrhea
Renal failure if severe hypotension occurs
Stomatitis
Mucositis
Source: Winn RL, Meiller TF, Crossley HL. Drug information handbook for dentistry, 15th ed. 2009. Hudson, Oh:
Lexicomp; Drugs.com. Drug information online. Available at:www.drugs.com. Accessed July 10, 2013.
22
Table Ic: MASCC/ISOO Mucositis Recommendations
Supported Recommendations
Resources NOT Recommended
Use of midline radiation blocks and 3 dimensional
radiation treatment
Chlorhexidine
Benzydamine for prevention of radiation-induced
mucositis for head and neck cancer patients
Antimicrobial lozenges
Sucralfate
Palifermin for those receiving high doses of
chemotherapy and total body irradiation with
autologous stem cell transplantation
Acyclovir
Cryotherapy to prevent mucositis in patients receiving
high-dose melphalin and other forms of chemotherapy
Granulocyte-macrophage-colony stimulating factor
(GM-CSF) mouthwashes
Pentoxifylline
Source: Keefe DM, Schubert MM, Elting LS, Sonis ST, et al. Updated clinical practice guidelines for the prevention
and treatment of mucositis. Cancer 2007;109:820-831.
23
Table 1d. BRONJ Staging and Treatment Strategies
BRONJ Staging
Treatment Strategies
At risk category – no apparent necrotic bone in patients
who have been treated with either oral or IV
bisphosphonates
•
•
No treatment indicated
Patient education
Stage 0 – no clinical evidence of necrotic bone, but
non-specific clinical findings and symptoms
•
Systemic management, including the use of
pain medication and antibiotics
Stage 1- exposed and necrotic bone in patients who
are asymptomatic and have no evidence of infection
•
•
•
Antibacterial mouth rinse
Clinical follow-up on a quarterly basis
Patient education and review of indications for
continued bisphosphonate therapy
Stage 2 – exposed and necrotic bone associated with
infection as evidenced by pain and erythema in the
region of the exposed bone with or without purulent
drainage
•
•
•
•
Symptomatic treatment with oral antibiotics
Oral antibacterial mouth rinse
Pain control
Superficial debridement to relieve soft tissue
irritation
Stage 3 – exposed or necrotic bone in patients with
pain, infection, and one or more of the following:
exposed and necrotic bone extending beyond the
region of alveolar bone, (i.e., inferior border and ramus
in the mandible, maxillary sinus and zygoma in the
maxilla) resulting in pathologic fracture, extra-oral
fistula, oral antral/oral nasal communication, or
osteolysis extending to the inferior border of the
mandible of sinus floor
•
•
•
Antibacterial mouth rinse
Antibiotic therapy and pain control
Surgical debridement/resection for longer
term palliation of infection and pain
Source: American Association of Oral and Maxillofacial Surgeons Position Paper on Bisphosphonate-Related
Osteonecrosis of the Jaw – 2009 Update. Available at: www.aaoms.org/docs/postion_papers/bronj_update.pdf.
Accessed July 14, 2014.
24
Figure 1a: Leading New Cancer Cases and Deaths – 2013 Estimates
25
Figure 1b: Survival Rates based on Stage at Diagnosis
26
Figure 1 c: Oral Cancer Pictorial Self-Exam
The AAOMS (American Association of Oral & Maxillofacial Surgeons) tells patients to perform
an oral cancer self-examination if any of the following symptoms are present:
•
difficulty in chewing or swallowing.
•
a chronic sore throat or hoarse voice that does not heal.
•
red patches in the mouth or on the tongue.
•
white patches in the mouth or tongue.
•
a lump or overgrowth of tissue anywhere in the mouth.
In order to complete a self examination for oral cancer, the AAOMS also recommends that one
use a bright light and mirror to perform the following:
•
Look inside the lips. Feel the tissue surfaces around the lips and cheeks.
•
Look at the gums from the front and using the small mirror, look at the tongue side
through another mirror, to view the inner gums. * By lifting your head back, look at the
roof of your mouth and feel with your forefinger if any bumps or growths are present.
Also note if any color changes are evident.
•
Take a gauze or tissue and gently pull your tongue out slowly. View all surfaces, top,
bottom, sides, to see if any color changes or if any red or white lesions are present. Also
note if any other abnormal changes are present, or if any wound takes too long to heal.
•
Feel for lumps in the neck and lower jaw region, on both sides.
Neck (head back): With your head
tilted back, look for masses or lumps.
Neck (head upright): With your head
upright, try to feel both sides of your
neck and under your jaw.
Lips: Feel the inside and outside of
your lip, using your thumb and
Gums: With your lips pulled away,
forefinger. Also look carefully as you
examine all the gums
do this.
27
Cheeks: Use your thumb and forefinger to pull your
Palate: Open wide to see the back and roof of your
cheeks away from your teeth.
mouth.
Tongue: Grab the end of your tongue with a tissue or
Tongue (upward): Raise the tip of your tongue to the roof
gauze. Pull your tongue out, right, and left, and
of your mouth. Check the floor of your mouth and under
examine each surface.
your tongue.
Always visit the dentist on a regular basis. (S)he will perform an oral cancer screening for you. If
you notice any abnormal problems or if you are not sure, visit the dentist at once. Early
detection is the key factor in treatment success.
From: Oral Cancer Pictorial Self-Exam. Available at: http://www.floss.com. Accessed July 10, 2013.
28

Maintaining Oral Health During Cancer Treatment JoAnn R. Gurenlian

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