Chemotherapy and Immune Suppression Flashcards
What do chemotherapy drugs expoit in order to be effective
Consequence of this
- Malignant cells behave differently to normal cells as they divide more rapidly
- Oral tissues with rapidly dividing cells are therefore often affected
- Oral Mucosa
- Hair Follicles
- Bone marrow
Future of chemotherapy
-Molecular biology is revealing subtle differences between malignant cells and other rapidly dividing tissues leading to development of targeted therapy
- eg.
- Cytotoxic monoclonal antibodies
Understanding of unique tumour architecture has allowed development of new therapy:
-Angiogenesis inhibitors
Chemotherapy for breast and prostate cancer
- Drugs developed that target the external processes that drive malignant growth
- Tamoxifen (Eostrogen Receptor Blocker): Breast Cancer
- Abiraterone (CYP17A1 enzyme inhibitor): Prostate Cancer
How do chemo drugs affect the cell cycle and benefit of this
- Different chemo drugs attack different parts of the cell cycle
- Multiple targets which they can attack
- Very useful having multiple sites of attack because cancers can mutate around it
- But we can just use another drug that attacks another part of the cell cycle
Types of Chemo and examples examples
Primary:
- Main modality of treatment
- For eg, leukaemia because it is everywhere
- Cannot be operated on surgically
Concurrent:
- Given with radiotherapy to increase radiosensitivity of the tumour
- So the tumour becomes more sensitive to the chemotherapy
Adjuvant:
- Given after surgery or radiotherapy
- Eliminates micrometastasis
- Prevents secondary tumours
Neo-adjuvant:
- Given before surgery or radiotherapy
- Reduces the tumour bulk
Aims of chemotherapy
To Cure:
- Acute Lymphoblastic Leukaemia (ALL)
- Burkitt’s Lymphoma
To Control:
- Prolonged remission
- Prevent relapse
Pallation:
- Prolong life
- Relieve symptoms
- Improve Quality of Life
Why are chemotherapy drugs given in combination
- If you give too much of any one of these drugs
- It will kill you as highly toxic
- Need to be given in low doses in combination
Hormone therapy and chemotherapy
Advantages and disadvantages
Dental Significance
Hormones are implicated in the aetiology and growth of some malignant tumours
- Breast
- Prostate
- Remove or reduce the hormone driving cell proliferation
- Block the hormone to cell receptor
Tamoxifen for breast blocks oestrogen eg
- Effect is confined to the target organ with minimal side effects
- Some tumours are resistant or develop resistance
-Minimal Oral effects
Targeted and Biological therapies goal
Target differences between normal tissue and tumours
Ideal Goal
- Specifically kill malignant cells
- No development of tumour resistance
- Minimise damage to other tissues
- Prolonged activity for maintenance therapy
Philadelphia Chromosome and significance of chemotherapy
- 90% of patients with Chronic Myeloid Lymphoma have a balanced translocation between chromosome 9 and 22
- Resultant oncogene with tyrosine kinase activity
- Lead to first targeted therapy for leukaemia
- Imatinib (tyrosine kinase inhibitor)
- Tyrosine kinase have a critical role in cell division and cell death
- Can be found on both the cell surface and intracellularly
- Sunitinib
- Imatinib
Tyrosine Kinase Inhibitors examples and side effects
- Imatinib
- Sunitinib
Sunitnib side effects include osteonecrosis of the jaw
Sunitinib drug definition, treatment and side effects
- Tyrosine Kinase Inhibitor
- First targetted treatment of CML
- Essentially starves the tumour of its blood supply
-Can cause osteonecrosis of the jaw because the jaw also requires a lot of blood supply
Significance of monoclonal antibodies in modern day chemotherapy
-Tumour associated with monoclonal antibodies
- Initally used for diagnosis
- Now used as a targeted treatment
- Often added to conventional chemotherapy
When can tumour vaccines be used
Examples
- Effective against virally induced tumours
- For example:
Hepatocellular Carcinoma can be treated with a Hep B vaccine
Burkits Lymphoma can be treated with an Epstein Barr Virus
Cervical Carcinoma can be treated with Human Papilloma Virus
Oropharyngeal Carcinoma
Human Papilloma Virus Vacine
Active Immune Therapy
-Immunisation to elicit an immune reaction to eliminate or delay tumour growth
Acute Side Effects of Chemo
General:
- Initially nausea and comiting (first few days)
- Fatigue throughout
Gastrointestinal:
- Oral mucositis
- Diarrhoea
Bone Marrow:
- Toxicity
- Neutrophils most affected
- Time course variable
- Anaemia
- Low platelets level
- Coagulopathy
Hair Follicles
-Alopecia
Long Term Effects of Chemotherapy and significance
- Patients now survive after advanced malignancy
- Need to minimise long term toxicity of the treatment
- Can detract from QoL (eg. osteonecrosis of the jaw), shorten life expectancy
- Surveillance for long term toxic effects may need to be continued for many decades
- Infertility
- Premature menopause
- Cardiotoxicity
- Pulmonary Fibrosis
- Teratogenicity
- Neurological
- Hearing Loss
- Secondary Malignancy
- Chronic Kidney Disease
Why is the oral cavity affected in chemotherapy
-High turnover rate of lining (Significantly higher than skin)
- Non keratinised areas most affected
- Highly sensate mucosa
- Constant immunological challenge
Significance of oral effects
- Low mood
- Social isolation
- Inability to complete cancer treatment
- Impaired nutrition
Oral complications of chemotherapyh
Oral Mucositis:
- Acute complication
- Most common
Oral Infection:
- Viral, fungal or bacterial
- Acute complication
Taste Disturbance:
-Acute complication
Salivary Gland Dysfunction:
-Acute
Neuropathy
- Acute
- Jaw pain may occur with vinca alkaloids
Haemorrhage
- Acute complication
- Haemorrhage may occur with oral mucositis
- Oral infections and/or thrombocytopenia
Dental/Skeletal Developmental Problems
- Chronic complication
- Sometimes in paediatric patients
Second Malignancy
-Chronic complication
Mucositis clinical features
- Widespread ulceration
- Intolerable pain
- Worst side effect often
Risk Factors for developing mucositis
- Poor Oral Health (main one)
- Female
- Caucasian
- Poor nutrition
- Young age
- Type of cancer
- Type of chemo
- Multicycle treatment
- Genetic factors
- Combined radiotherapy
How do you classify severity of mucositis
Grade 1 -4
-Look at slides not sure we need to know but
1: Oral Soreness, Erythema
2: Can swallow foods but ulcers as well
3: Cannot swallow foods or extensive ulcers
4: Alimentation not possible
How to manage a patient with mucositis
- Optimum oral health (soft toothbrush and careful flossing )
- Cryotherapy (chewing ice cubes)
- Chlorhexadine mouth rinse
- LA mouth rinse
- Keratinocyte stimulator
- Opiate pain killers
- PEG feeding
- Abandon chemotherapy if that bad
Drugs used to support chemotherapy that we should be aware of
- Bisphosphonates
- Tyrosine Kinase Inhibitors such as Sunitinib
-Both can cause osteonecrosis of the jaw
Things to be aware of if a patient says theyve had chemo
- Was it to cure or control/palliate
- Indicates QoL etc
- Any drugs used to support chemo such as bisphosphonates or sunitinib which can cause osteonecrosis
- Did the patient receive significant head and neck radiotherapy? Xerostomia/osteonecrosis
Long term oral complications of chemo
- Not many
- Minimal
Immunosuppression v immunodeficient v immunocompromised
Immunosuppression
-Artificially depressed immune system
Immunodeficient
-Any state in which the immune system is below optimum level
- Immunocompromised
- Poor immune function due to disease/medications
Types of immunodeficiency
Congenital (Innate)
- Rare
- Uncommon with significant variability in severity and oral impact
Acquired (Secondary)
- Common due to disease or treatment of disease
- HIV, Leukaemia, Autoimmunity
- Diabetes, Sickle Cell
- Malnutrition
- Post organ transplant
- Treatment of Malignancy
Common Drugs used in Immune Suppression
Corticosteroids
-Prednisolone
Calcineuric Inhibitors
- Cyclosporin
- Tacrolimus
Antiproliferative Agents
-Azathioprine
Antimetabolites
-Methotrexate
Antibodies/Anti TNF
-Inflixamab
Common uses of immunosuppression
-Prevent transplant rejection
-Cancer chemotherapy
-Treatment of autoimmune diseases
eg
Multiple Sclerosis
Inflammatory Bowel Disease
Rheumatoid Arthritis
Systemic Lupus Erythematosis (SLE)
Sjorgens syndrome
Corticosteroids examples, definition and side effects
- Non SPECIFIC anti inflammatory
- eg. Prednisolone
- Trying to limit use and reduce dose because many side effects
- Hypertension
- Fluid Retention
- Osteoporosis
- Diabetes
- Cushingoid Appearance
- Infections
- Weight Gain
-High doses of steroids may lead to Cushings Syndrome
Immune Suppression drugs and affect in terms of dentistry
- Often mask the symptoms of the infection
- Might not feel too bad
- Increased susceptibility to infection
How can exogenous steroids lead to addisonian crisis
- If they withdraw from taking exogenous steroids
- Body is not used to making their own cortisol
- For example prednisolone
- Atrophy with reduced steroid production
- Low glucocorticoids leading to low blood pressure and low blood sugar
- Collapse
Is Addisonian risk significant to dentists
- Normally precipitated by a stressful event
- Acute infection or major trauma
- Dental treatment is not stressful enough
- GA and major surgery may pose a risk
-No good evidence to support administering a booster dose of steroid in dentistry, despite what dental literature says
Steroid sparing drugs and significance
- Alternating drugs that help to reduce the steroid dose
- Reducing side effects
Azathioprine Methotrexate Mycophenolate Retuximab Inflixamab
Specific and Generalised oral side effects of immunosuppressents
Specific:
Gingival Hyperplasia of Cyclosporin
Generalised
- Candida
- Oral ulceration
- Herpes simplex/zoster, EBV and CMV
- Delayed wound healing
- Periodontal disease
- Potential malignancies
Herpes Simplex and immunosuppression, treatment/prevention
- Most common viral pathogen causing oral infection
- 2-6 weeks post transplant
- More severe than in normal patients
- May develop vesicles on keratinised areas
Tx:
-Acyclovir
Epstein-Barr Virus Oral manifestations and treatment
Oral Hairy Leukoplakia
Antiviral meds or reduce immunosuppression
Candida infection treatment
- Nystatin Suspension
- Fluconazole
Cyclosporin and gingival hyperplasia mechanism and tx
- Increases collagen and glycosaminoglycan synthesis
- Affects anterior regions most
- Mandible>Maxilla
Treatment
- Improve OH
- Alternative drugs
- Surgical reduction
Graft Veruss Host Disease
- Immunocompetent graft attacking immunodeficient host
- Can be acute or chronic
- Oral lesions in 80%
- Lichenoid reactions
- Ulcerations
- Candida
- Hyperkeratotic Leukoplakia
- Fibrosis leading to trismus
- Salivary gland dysfunction
Common malignancies and relation to immunosuppresion
- Occurs in 3-30% of transplant patients
- Lip squamous cell cancer (SCC) most common
- Intra oral SCC
- Basal Cell cancer (BCC)
- Kaposi’s Sarcoma
Infection and immune suppression
- Depends on type of immue suppression
- Prophylactic antibiotics may be required for surgical/invasive procedures
- Pt may feel well despite evidence of significant infection
Relevant Blood Tests and Staging Extractions
-Aim to carry out extractions 10 days before neutrophil count <0.5
