Modes of treatment Flashcards
What are the priorities when dealing with cancer?
Prevention,
Early Detection,
Total Eradication
What is the hierarchy of aims in cancer management?
Cure - eradication of tumour and metastasis.
Remission/mitigation - significant reduction in tumour load. Increased survival.
Symptomatic / palliation - treatment of secondary complications. Relief of symptoms.
Terminal care - improve quality of life. Optimize symptom control.
why is there no sufficient cure for most solid tumours? What happens
For most solid tumours local control is possible but not sufficient for cure because of the presence of systemic (microscopic) disease, while haematological cancers are usually disseminated from the outset.
Which cancers are super sensitive to chemo that bulky metastases can be cured and which ones are not?
leukaemia and lymphoma = chemosensitive
Breast and colorectal = no current cure
What is Palliation and when does it occur?
When cure is no longer possible, palliation, i.e. relief of tumour symptoms and prolongation of life
What are the modes of therapy? (4)
- Surgery - excision of primary tumour.
- Bone marrow transplantation - for some leukaemias.
- Radiotherapy
- Drugs - cytotoxic chemotherapy, hormone therapy, immunotherapy.
What are the factors that govern which treatment is used?
- empirical clinical evidence;
2. practical considerations
When is surgery used?
Well-defined solid tumour
Non-vital region (e.g. mastectomy)
Non-mutilating result
Resection/reconstruction possible (e.g. gut)
When is radiotherapy used?
Diffuse but localized tumour (e.g. lymphoma)
Vital organ / region (e.g. head and neck, CNS)
Adjuvant therapy (e.g. post mastectomy)
Palliation
When is chemotherapy used?
Adjuvant therapy following surgery or radiotherapy
Neo-adjuvant therapy prior to surgery or radiotherapy
Widely disseminated / metastasized
Diffuse tumour (e.g. leukaemia)
Palliation
Some primary tumours (e.g. Hodgkin’s lymphoma)
Why does chemotherapy cause the hair to fall out?
Kill cells that rapidly divide. NOT tumour specific so also kill normal rapidly dividing cells such as hair follicle cells and gastrointestinal mucosa
How does Radiotherapy work? Give examples
application of ionizing radiation to treat disease - electromagnetic radiation and elementary particles deposit energy in materials through the processes of excitation and ionization events. Common forms of ionizing radiation include photon beams (X-rays and gamma rays) and electrons (b-particles).
Cell death = approx 40 double strand breaks in DNA
What are the palliative benefits of radiotherapy? (5)
- Pain relief e.g. bone metastases.
- Reduction of headache and vomiting of raised intracranial pressure from CNS metastases.
- Relief of obstruction of bronchus, oesophagus, ureter and lymphatics.
- Preservation of skeletal integrity from metastases in weight-bearing bones.
- Reversal of neurological impairment from spinal cord or optic nerve compression by metastases.
What are the acute side effects of radiotherapy?
anorexia, nausea, malaise
Mucositis, e.g. oesophagitis, diarrhoea
Alopecia
Myelosuppression
What are the later side effect of radiotherapy?
Skin : Ischaemia, ulceration Bone : Necrosis, fracture Mouth : Xerostomia, sialitis, ulceration Bowel : Stenosis, fistula, diarrhoea Bladder : Cystitis Vagina : Dyspareunia, stenosis Lung : Fibrosis Heart : Pericardial fibrosis, cardiomyopathy CNS : Myelopathy Gonads : Infertility, menopause
Describe the rationale for the use of chemotherapy?
For the majority of the solid tumours chemotherapy is used to reduce the volume of disease and palliative symptoms caused by cancer.
A further indication for chemotherapy is to use it as an adjuvant after the primary tumour has been controlled by either surgery or radiotherapy - this is to eradicate subclinical micrometastatic disease and reduce the risk of recurrence.
Neoadjuvant chemotherapy is also used increasingly to debulk or downstage primary tumours prior to the definitive treatment, eg surgery or radiotherapy.
Chemotherapy is usually used systemically either intravenously or orally.
Define adjuvant therapy in relation to cancer
treatment given in the absence of macroscopic evidence of metastases, to patients at risk of recurrence from micrometastases
What is the time frame that chemotherapy should be given?
The treatment should be delivered on an intermittent basis with the shortest possible time between treatments that allows recovery of the most sensitive normal tissue (e.g. bone marrow or gut).
How can chemotherapy be given?
Wherever possible it is preferable to use drugs with known synergistic killing effects, for example the combination of oxaliplatin and 5-fluorouracil.
Another possibility is to use a combination of drugs that can kill cancer cells at different stages of the cell cycle.
Some regimens use alternating cycles of different drug combinations - giving the less effective drug first.
How do Microtubule inhibitors work? What stage of the cell cycle do they target? Give examples
Stop cells making components needed to separate
Target those in G2 phase
E.g. Vinca alkaloids, Docetaxol, Paclitaxel
How do Agents binding to DNA work? What stage of the cell cycle do they target? Give examples
Stop DNA synthesis
Target the S phase
e.g. Alkylating agents, anti-tumour antibiotics, platinum compounds
How do Anti-metabolites work? What stage of the cell cycle do they target? Give examples
Stop cells making the building blocks of DNA
Target G1 phase
e.g. methotrexate, azathioprine
What are the side effects of chemotherapy cytotoxic action?
Myelosuppression - rapid fall in blood count with a nadir for WBC and platelets at 7 days.= frequent infections, impairs coagulation leading to bruising + bleeding
GI tract + bladder - erosion and ulceration in mucous membranes = mouth ulcers and diarrhoea
Skin + Hair - hair loss common, reversible
Fertility - Spermatogenesis is inhibited and sometimes there may be permanent male infertility, e.g. from alkylating agents. Female infertility is less common
Teratogenic action - cytotoxics are particularly hazardous during the first trimester of pregnancy, I.e. during organogenesis and the risk is greatest for methotrexate and the alkylating agents
What are the side effects of chemotherapy -mutagenesis?
Genetic damage - heritable defects may be caused if the DNA of spermatazoa or ova is damaged, although most mutations are lethal for the cell. These risks are yet to be fully assessed but are avoided by contraception during treatment.
Carcinogenesis - cytotoxic drugs are able to both cause and cure cancer. The same is true for radiotherapy. Hence more selective methods for treating cancer are required
