Cancer Treatments Flashcards
What is the difference between adjuvant and neoadjuvant treatment?
Adjuvant is the additional therapy given with/after main treatment
Neoadjuvant is given prior to main treatment to reduce tumour size
What are the advantages and disadvantages of neoadjuvant therapy?
- Can do more conservative surgery
- Chemo response can predict outcome
- May overtreat
- Disease may progress
What are the advantages and disadvantages of Adjuvant therapy?
- Immediate surgical removal
- Bigger surgery may be needed
- Can’t measure efficacy of chemo/radio before
What different methods of radiotherapy can be given?
External beam (EBRT)
Brachytherapy
Systemic (Injected/swallowed)
How is radiotherapy dose defined?
Irradiation absorbed by 1kg of tissue. Expressed in Grays (Gy)
Why are radiotherapy doses given in fractions?
Highest total dose delivered to tumour but normal tissue preferentially spared
What are some acute toxicities of radiotherapy?
Fatigue Moist desquamation of the skin Oral mucositis Pneumonitis N&V Cytopenia can occur in whole body radiation
What are some long term effects of radiotherapy?
Secondary cancer!!
Others tend to relate to area be radiated: Fibrosis leading to reduced ROM Lymphedema Infertility Hypothyroidism Dry eyes and cataract Atrophy Neural or vascular damage Endocrine side effects
When might radiotherapy be used in a palliative setting?
Palliation of symptoms e.g.
To a tumour causing spinal cord compression reducing neuropathic symptoms
To bony mets to reduce pain
How does radiation cause cell death?
Apoptosis by causing significant DNA damage
Preventing cancer cell proliferation, causing single and double stranded breaks in DNA
What specific head and neck radiotherapy side effects?
Dysphagia Jaw stiffness Dry mouth Mouth and gum sores Hair loss Lymphoedema Tooth decay
What are the specific side effects of chest radiotherapy?
Dysphagia
Dyspnoea
Radiation pneumonitis - can manifest as cough, chest pain, fevers
Radiation fibrosis - result of permanent lung scarring as a result of untreated radiation pneumonitis
What are some specific side effects of abdominal radiotherapy?
Nausea and vomiting
Diarrhoea
Loss of appetite
Abdominal cramping
What is the mechanism of action of chemotherapy agents?
Disrupt various parts of the cell cycle
G1 growth
S DNA synthesis
G2 growth and prep for mitosis
M mitosis cell division
What are some of the side effects of chemo?
Bone marrow suppression - pancytopenia, risk of neutropenic sepsis
Due to rapid turnover of cells involved in haemopoiesis
Increased apoptosis in rapidly dividing epithelial cells in oral mucosa and intestine = mucosal damage
Mucositis, malabsorption, diarrhoea
Acts on CTZ causing nausea and vomiting
Chemo induced damaged to the rapidly dividing cells in the hair root - hair loss
What are the classes of chemo agents (by mechanism of action) and some examples?
—- Antimetabolites —-
Pyrimidine antagonists - inhibit thymidine synthase and halt DNA replication
e.g. Gemcitabine, 5-FU
Purine antagonists
6-mercaptopurine, azathioprine - measure TMPT levels before as deficiency of this could cause toxicity
Folate antagonists
Methotrexate
Ribonucleotide reductase inhibitors e.g. hydroxyurea in CML
—- Alkylating Agents —-
Act on DNA cause cross linking and cell death
Cyclophosphamide - breast, ovarian, SCLC
Platinum agents e.g. cisplatin, carboplatin, oxaliplatin
Nitrogen mustards - chlorambucil, melphalan
—- Topoisomerase inhibitors —-
—- Mitotic inhibitors —-
Act on microtubules
Cause myelosuppression and neurotoxicity
Vinca alkaloids - vincristine
Taxanes - paclitaxel
—- Antibiotics —–
Derived from antibiotic agents
Mitomycin C
Bleomycin - testicular cancer
Anthracyclines - doxorubicin
(Breast ca or NHL)
—- Protein kinase inhibitors —-
BCR-ABL - imatinib for CML
EGFRs - erlotinib, lung cas
Brunton - Ibrutinib - CLL
What is palmar plantar erythrodysesthesia?
Painful erythematous rash
Occurs over palms, fingers and soles of feet
Lesions clearing demarcated, painful
Skin breakdown, blistering develops
Dose related side effect
Management is supportive, use of emollients and steroid creams to reduce inflammation
What patient factors must be considered before initiating chemo?
Performance status Reaction to previous cycles Bloods Co-morbidities - esp. liver & kidney Surface area/BMI of patient
How can cancers develop resistance to chemotherapy agents?
Increased efflux Decreased influx Alter drug target Enhance DNA repair Drug detoxification
What are some long term side effects of chemotherapy?
Chemo brain Early menopause Decreased lung capacity Osteoporosis Muscle weakness Congestive HF Hearing loss Secondary Cancer
What are the principles of immunotherapy?
Actively stimulate the immune system
Passively alter the immune system signalling
Treatment targeted at specific known antigenic targets or stimulating the immune system non-specifically
What are the types of immunotherapy?
Monoclonal antibodies Checkpoint inhibitors Cytokines Vaccinations - clinical trials CAR T-cell therapy
How do monoclonal antibodies work?
MAB recognises and finds specific proteins on cells
Either triggers immune system to attack and kill cancer cells
Or attach to cancer cells, making it easier for cells of immune system to find and attack
What are some examples of MABs?
Rituximab for CLL and some types of NHL
Cetuximab for advanced bowel, head and neck cancer
Trastuzumab - Herceptin for breast cancer, stomach cancer
How do checkpoint inhibitors work?
Block the signals that switch off lymphocytes
Some cancer cells have the ability to deactivate T cells
Blocks protein meaning T cells can function again
What are some side effects of checkpoint inhibitors and how are they managed?
Because the drugs boost the immune system, side effects are generally autoimmune and therefore managed with CORTICOSTEROIDS
- diarrhoea
- dermatitis
- hypothyroid, adrenal
- hepatitis
- pneumonitis
What are some examples of checkpoint inhibitors?
Nivolumab, pembrolizumab on PD-1 - melanoma, HL, NSCLC
Avelumab, atezolizumab
PDL-1
lung cancer, urinary tract
What is cytokine immunotherapy?
Interferon
Kidney cancer, leukaemia, skin lymphoma
Interferes with the way cancer cells grow and multiply, stimulates immune system, encourages cancer cells to produce chemicals
Given as injection under the skin or infusion
3 times a week
Aldesleukin - interleukin 2
Kidney cancer
What are the side effects of interferon and aldesleukin?
Drop in blood cells causing increased risk of infection, bleeding problems, tiredness, breathlessness Flu like symptoms Diarrhoea Tiredness and weakness Feeling sick Loss of appetite
